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Organ From Live Donor Best When Child Needs New Kidney

Title: Organ From Live Donor Best When Child Needs New Kidney
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM




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Treating central sleep apnoea in heart failure: progressing one step at a time

Extract

We read with great interest the correspondence by T. Bitter and co-workers in the European Respiratory Review, about our recently published review entitled "Central sleep apnoea: not just one phenotype" [1]. We first want to express our gratefulness to the authors for their support and appreciation of our work, particularly regarding the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine.




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Treating central sleep apnoea in heart failure: is positive airway pressure and adaptive servo-ventilation in particular the gold standard?

Extract

We read with great interest the review article by Randerath et al. [1] recently published in the European Respiratory Review. We would like to congratulate the authors on this clearly structured review, which emphasises the urgent need for an increasingly differentiated view of central sleep apnoea (CSA) in the context of precision medicine.




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Wonca Europe 2023 Definition of General Practice/Family Medicine: New Needs New Content




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How Early Career Family Medicine Women Physicians Negotiate Their First Job After Residency

Background:

Nested within a growing body of evidence of a gender pay gap in medicine are more alarming recent findings from family medicine: a gender pay gap of 16% can be detected at a very early career stage. This article explores qualitative evidence of women’s experiences negotiating for their first job out of residency to ascertain women’s engagement with and approach to the negotiation process.

Methods:

We recruited family physicians who graduated residency in 2019 and responded to the American Board of Family Medicine 2022 graduate survey. We developed a semistructured interview guide following a modified life history approach to uncover women’s experiences through the transitory stages from residency to workforce. A qualitative researcher used Zoom to interview 19 geographically and racially diverse early career women physicians. Interviews were transcribed verbatim and analyzed using NVivo software following an Inductive Content Analysis approach.

Results:

Three main themes emerged from the data. First, salary was found to be nonnegotiable, exemplified by participants’ inability to change initial salary offers. Second, the role of peer support throughout residency and early career was crucial to uncovering and rectifying salary inequity. Third, a pay expectation gap was identified among women from minority and low-income households.

Conclusion:

To rectify the gender pay gap in medicine, a systems-level approach is required. This can be achieved through various levels of interventions: societally expanding the use of and removing the stigma around parental leave, recognizing the importance of contributions not currently valued by productivity-based payment models, examining assumptions about leadership; and institutionally moving away from fee-for-service systems, encouraging flexible schedules, increasing salary transparency, and improving advancement transparency.




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Clinician-Reported Barriers and Needs for Implementation of Continuous Glucose Monitoring

Background:

Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved clinical, behavioral, and psychosocial patient health outcomes and is part of the American Diabetes Association’s Standards of Medical Care. CGM prescription often takes place in endocrinology practices, yet 50% of adults with type 1 diabetes and 90% of all people with type 2 diabetes receive their diabetes care in primary care settings. This study examined primary care clinicians’ perceptions of barriers and resources needed to support CGM use in primary care.

Methods:

This qualitative study used semistructured interviews with primary care clinicians to understand barriers to CGM and resources needed to prescribe. Participants were recruited through practice-based research networks. Rapid qualitative analysis was used to summarize themes from interview findings.

Results:

We conducted interviews with 55 primary care clinicians across 21 states. Participants described CGM benefits for patients with varying levels of diabetes self-management and engagement. Major barriers to prescribing included lack of insurance coverage for CGM costs to patients, and time constraints. Participants identified resources needed to foster CGM prescribing, for example, clinician education, support staff, and EHR compatibility.

Conclusion:

Primary care clinicians face several challenges to prescribing CGM, but they are interested in learning more to help them offer it to their patients. This study reinforces the ongoing need for improved clinician education on CGM technology and continued expansion of insurance coverage for people with both type 1 and type 2 diabetes.




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Colorectal Cancer Screening: A Multicomponent Intervention to Increase Uptake in Patients Aged 45-49

Purpose:

Colorectal cancer (CRC) screening is recommended starting at age 45, but there has been little research on strategies to promote screening among patients younger than 50. This study assessed the effect of a multicomponent intervention on screening completion in this age group.

Methods:

The intervention consisted of outreach to patients aged 45 to 49 (n = 3,873) via mailed fecal immunochemical test (FIT) (sent to 46%), text (84%), e-mail (53%), and the extension to this age group of an existing standing order protocol allowing primary care nurses and medical assistants to order FIT at primary care clinics in an urban safety-net system. We used segmented linear regression to assess changes in CRC screening completion trends. Patients aged 51 to 55 were included as a comparison group (n = 3,943). Data were extracted from the EHR.

Results:

The percentage of patients aged 45 to 49 who were up-to-date with CRC screening (colonoscopy in 10 years or FIT in last year) increased an average of 0.4% (95% CI 0.3, 0.6)) every 30 days before intervention rollout and 2.8% (95% CI 2.5, 3.1) after (slope difference 2.3% [95% CI 2.0, 2.7]). This difference persisted after accounting for small changes in the outcome observed in the comparison group (slope difference 1.7% [95% CI 1.2, 2.2]).

Conclusions:

These results suggest that the intervention increased CRC screening completion among patients 45 to 49. Health care systems seeking to improve CRC screening participation among patients aged 45 to 49 should consider implementing similar interventions.




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Implementation of an Opt-Out Outpatient HIV Screening Program

Background:

Screening rates for Human Immunodeficiency Virus (HIV) remain low despite guidelines by both the CDC and USPSTF recommending that all adolescents and adults be screened at least once. The aim of this quality improvement study was to increase HIV screening among eligible patients.

Methods:

This quality improvement study assessed the impact of interventions to increase HIV screening in an outpatient population at a large urban safety-net hospital. Outcomes were compared from the preintervention (December 2020 to November 2021) to postintervention years (December 2021 to November 2022). Stepwise electronic alerts to prompt HIV screening paired with provider financial incentives were implemented. The proportion of eligible individuals screened for HIV were compared after intervention implementation.

Results:

Average monthly HIV screening increased from 506 ± 97 to 2484 ± 663 between the pre- and postintervention periods, correlating to a 5.1-fold increase in screening (7.8% to 39.8%, P < .01). Increases were seen across all ages, and those aged 55 to 64 and 65+ had the highest relative increase in screening at 7.5 and 9.3-fold, respectively (P < .01). Screening rates increased for Hispanics (7.9% preintervention vs 43.6% postintervention, P < .01). In the pre- and postintervention periods, 41 patients with new HIV diagnoses were identified (13 preintervention and 28 postintervention) and 85.4% were linked to care within 30 days.

Conclusions:

Stepwise interventions targeted at primary care clinicians are an effective way to increase HIV screening rates, particularly in older demographics. Earlier HIV diagnosis coupled with linkage to care is an important strategy in ending the HIV epidemic.




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Associations Between Patient/Caregiver Trust in Clinicians and Experiences of Healthcare-Based Discrimination

Background:

Higher trust in healthcare providers has been linked to better health outcomes and satisfaction. Lower trust has been associated with healthcare-based discrimination.

Objective:

Examine associations between experiences of healthcare discrimination and patients’ and caregivers of pediatric patients’ trust in providers, and identify factors associated with high trust, including prior experience of healthcare-based social screening.

Methods:

Secondary analysis of cross-sectional study using logistic regression modeling. Sample consisted of adult patients and caregivers of pediatric patients from 11 US primary care/emergency department sites.

Results:

Of 1,012 participants, low/medium trust was reported by 26% identifying as non-Hispanic Black, 23% Hispanic, 18% non-Hispanic multiple/other race, and 13% non-Hispanic White (P = .001). Experience of any healthcare-based discrimination was reported by 32% identifying as non-Hispanic Black, 23% Hispanic, 39% non-Hispanic multiple/other race, and 26% non-Hispanic White (P = .012). Participants reporting low/medium trust had a mean discrimination score of 1.65/7 versus 0.57/7 for participants reporting high trust (P < .001). In our adjusted model, higher discrimination scores were associated with lower trust in providers (aOR 0.74, 95%CI = 0.64, 0.85). A significant interaction indicated that prior healthcare-based social screening was associated with reduced impact of discrimination on trust: as discrimination score increased, odds of high trust were greater among participants who had been screened (aOR = 1.28, 95%CI = 1.03, 1.58).

Conclusions:

Patients and caregivers reporting more healthcare-based discrimination were less likely to report high provider trust. Interventions to strengthen trust need structural antiracist components. Increased rapport with patients may be a potential by-product of social screening. Further research is needed on screening and trust.




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Reply to Letter to Editor Concerning &#x201C;Nocturnal Pressure Controlled Ventilation Improves Sleep Efficiency in Patients Receiving Mechanical Ventilation&#x201D;




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The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS

BACKGROUND:PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS.METHODS:Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected.RESULTS:A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8–12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O).CONCLUSIONS:Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.




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Comparison of Needle Depth Techniques for the Posterior Superior Alveolar Block

Purpose The posterior superior alveolar (PSA) block injection is one of many techniques used to provide profound anesthesia for invasive dental procedures. This technique has a high success rate but is not without complication risks. The purpose of this study was to determine if pulpal anesthesia of the maxillary second molar could be achieved using a reduced needle depth of 10mm or 5mm compared to the traditional needle depth of 16mm.Methods Sixty participants were asked to participate in three sessions. Each session started with a pre neural response test, followed by one randomized needle depth PSA injection, and ending with a post neural response test. The neural response test consisted of two parts, a cold refrigerant and a dental probe, on the buccal and interproximal surface of the maxillary second molar. After receiving a positive neural response, each participant received a posterior superior alveolar block injection using a short (21mm), 27-gauge dental needle with a randomized needle penetration depth of 16mm, 10mm, or 5mm. A post neural response test consisting of the same two parts as the pre-test was conducted on the maxillary second molar to evaluate for profound anesthesia.Results Positive neural responses were obtained from 100% of the participants (n=167) during the pre-tests. Study results demonstrated an 85% success rate at the traditional 16mm needle depth and a 93% and 92% success rates for the reduced needle depths of 10mm and 5mm, respectively. Pulpal anesthesia of the maxillary second molar had been achieved at all three needle depths with no statistically significant difference in the rate of success. Furthermore, there were no adverse events observed.Conclusion The reduced needle depth technique showed promise in achieving desired results of pulpal anesthesia with a reduced risk for complications associated with the PSA block injection. Additional studies are recommended to achieve evidence-based support for this reduced needle depth technique.




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A circular split nanoluciferase reporter for validating and screening putative internal ribosomal entry site elements [METHOD]

Internal ribosomal entry sites (IRESs) recruit the ribosome to promote translation, typically in an m7G cap-independent manner. Although IRESs are well-documented in viral genomes, they have also been reported in mammalian transcriptomes, where they have been proposed to mediate cap-independent translation of mRNAs. However, subsequent studies have challenged the idea of these "cellular" IRESs. Current methods for screening and discovering IRES activity rely on a bicistronic reporter assay, which is prone to producing false positive signals if the putative IRES sequence has a cryptic promoter or cryptic splicing sites. Here, we report an assay for screening IRES activity using a genetically encoded circular RNA comprising a split nanoluciferase (nLuc) reporter. The circular split nLuc reporter is less susceptible to the various sources of false positives that adversely affect the bicistronic IRES reporter assay and provides a streamlined method for screening IRES activity. Using the circular split nLuc reporter, we find that nine reported cellular IRESs have minimal IRES activity. Overall, the circular split nLuc reporter offers a simplified approach for identifying and validating IRESs and exhibits reduced propensity for producing the types of false positives that can occur with the bicistronic reporter assay.




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Improved functions for nonlinear sequence comparison using SEEKR [ARTICLE]

SEquence Evaluation through k-mer Representation (SEEKR) is a method of sequence comparison that uses sequence substrings called k-mers to quantify the nonlinear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimate P-values that ascribe statistical significance to SEEKR-derived similarities, as well as visualize different aspects of k-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that contain XIST-like sequence features, and we demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and we outline the best practice of visualizing RNA-seq read density to evaluate support for lncRNA annotations before their in-depth study in cell types of interest.




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Association between a recalled positive airway pressure device and incident cancer: a population-based study

Background

The real-world consequences of a Philips Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown.

Methods

We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death or end of follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups.

Results

Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices and 173 488 (74.9%) claimed devices from other manufacturers. A meaningful baseline difference between groups (standardised difference ≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences ≤0.06). Over a median (interquartile range) follow-up of 6.3 (4.9–8.0) years, 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 person-years of 78.8 (95% CI 76.0–81.7) in the recall group versus 74.0 (95% CI 72.4–75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences ≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) 0.97 (95% CI 0.89–1.06).

Conclusion

In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled Philips Respironics PAP devices do not appear to be independently associated with developing cancer.




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Simplified Method for Kinetic and Thermodynamic Screening of Cardiotonic Steroids through the K+-Dependent Phosphatase Activity of Na+/K+-ATPase with Chromogenic pNPP Substrate [Article]

The antitumor effect of cardiotonic steroids (CTS) has stimulated the search for new methods to evaluate both kinetic and thermodynamic aspects of their binding to Na+/K+-ATPase (IUBMB Enzyme Nomenclature). We propose a real-time assay based on a chromogenic substrate for phosphatase activity (pNPPase activity), using only two concentrations with an inhibitory progression curve, to obtain the association rate (kon), dissociation rate (koff), and equilibrium (Ki) constants of CTS for the structure-kinetics relationship in drug screening. We show that changing conditions (from ATPase to pNPPase activity) resulted in an increase of Ki of the cardenolides digitoxigenin, essentially due to a reduction of kon. In contrast, the Ki of the structurally related bufadienolide bufalin increased much less due to the reduction of its koff partially compensating the decrease of its kon. When evaluating the kinetics of 15 natural and semisynthetic CTS, we observed that both kon and koff correlated with Ki (Spearman test), suggesting that differences in potency depend on variations of both kon and koff. A rhamnose in C3 of the steroidal nucleus enhanced the inhibitory potency by a reduction of koff rather than an increase of kon. Raising the temperature did not alter the koff of digitoxin, generating a H (koff) of –10.4 ± 4.3 kJ/mol, suggesting a complex dissociation mechanism. Based on a simple and inexpensive methodology, we determined the values of kon, koff, and Ki of the CTS and provided original kinetics and thermodynamics differences between CTS that could help the design of new compounds.

SIGNIFICANCE STATEMENT

This study describes a fast, simple, and cost-effective method for the measurement of phosphatase pNPPase activity enabling structure-kinetics relationships of Na+/K+-ATPase inhibitors, which are important compounds due to their antitumor effect and endogenous role. Using 15 compounds, some of them original, this study was able to delineate the kinetics and/or thermodynamics differences due to the type of sugar and lactone ring present in the steroid structure.




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The Dawning of a New Age of Preclinical Analgesic Drug Screening [Viewpoint]




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Freehand SPECT Combined with 3-Dimensional Light Detection and Ranging as Alternative Means of Specimen Scanning During Prostate Cancer Surgery




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Association of Free-to-Total PSA Ratio and 18F-DCFPyL Prostate-Specific Membrane Antigen PET/CT Findings in Patients with Biochemical Recurrence After Radical Prostatectomy: A Prospective Single-Center Study

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0–72.4 y), and the median PSA at 18F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3–0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96–16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.




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Deep Learning-Based Reconstruction of 3D T1 SPACE Vessel Wall Imaging Provides Improved Image Quality with Reduced Scan Times: A Preliminary Study [ARTIFICIAL INTELLIGENCE]

BACKGROUND AND PURPOSE:

Intracranial vessel wall imaging is technically challenging to implement, given the simultaneous requirements of high spatial resolution, excellent blood and CSF signal suppression, and clinically acceptable gradient times. Herein, we present our preliminary findings on the evaluation of a deep learning–optimized sequence using T1-weighted imaging.

MATERIALS AND METHODS:

Clinical and optimized deep learning–based image reconstruction T1 3D Sampling Perfection with Application optimized Contrast using different flip angle Evolution (SPACE) were evaluated, comparing noncontrast sequences in 10 healthy controls and postcontrast sequences in 5 consecutive patients. Images were reviewed on a Likert-like scale by 4 fellowship-trained neuroradiologists. Scores (range, 1–4) were separately assigned for 11 vessel segments in terms of vessel wall and lumen delineation. Additionally, images were evaluated in terms of overall background noise, image sharpness, and homogeneous CSF signal. Segment-wise scores were compared using paired samples t tests.

RESULTS:

The scan time for the clinical and deep learning–based image reconstruction sequences were 7:26 minutes and 5:23 minutes respectively. Deep learning–based image reconstruction images showed consistently higher wall signal and lumen visualization scores, with the differences being statistically significant in most vessel segments on both pre- and postcontrast images. Deep learning–based image reconstruction had lower background noise, higher image sharpness, and uniform CSF signal. Depiction of intracranial pathologies was better or similar on the deep learning–based image reconstruction.

CONCLUSIONS:

Our preliminary findings suggest that deep learning–based image reconstruction–optimized intracranial vessel wall imaging sequences may be helpful in achieving shorter gradient times with improved vessel wall visualization and overall image quality. These improvements may help with wider adoption of intracranial vessel wall imaging in clinical practice and should be further validated on a larger cohort.




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Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial [RESEARCH]

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

MATERIALS AND METHODS:

This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA.

RESULTS:

Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result.

CONCLUSIONS:

This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself.




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Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera [RESEARCH ARTICLE]

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.




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Deep molecular tracking over the 12-yr development of endometrial cancer from hyperplasia in a single patient [RESEARCH REPORT]

Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels.




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Phosphate-Buffered Saline with Tween and BSA (PBSTB)




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Phosphate-Buffered Saline with Tween (0.1%) (PBST)




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Analysis of Sleep and Circadian Rhythms from Drosophila Activity-Monitoring Data Using SCAMP

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.




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Neural Stimulation during Drosophila Activity Monitor (DAM)-Based Studies of Sleep and Circadian Rhythms in Drosophila melanogaster

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila, how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells.




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Activity Monitoring for Analysis of Sleep in Drosophila melanogaster

Sleep is important for survival, and the need for sleep is conserved across species. In the past two decades, the fruit fly Drosophila melanogaster has emerged as a promising system in which to study the genetic, neural, and physiological bases of sleep. Through significant advances in our understanding of the regulation of sleep in flies, the field is poised to address several open questions about sleep, such as how the need for sleep is encoded, how molecular regulators of sleep are situated within brain networks, and what the functions of sleep are. Here, we describe key findings, open questions, and commonly used methods that have been used to inform existing theories and develop new ways of thinking about the function, regulation, and adaptability of sleep behavior.




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Engineering of Affibody Molecules

Affibody molecules are small, robust, and versatile affinity proteins currently being explored for therapeutic, diagnostic, and biotechnological applications. Surface-exposed residues on the affibody scaffold are randomized to create large affibody libraries from which novel binding specificities to virtually any protein target can be generated using combinatorial protein engineering. Affibody molecules have the potential to complement—or even surpass—current antibody-based technologies, exhibiting multiple desirable properties, such as high stability, affinity, and specificity, efficient tissue penetration, and straightforward modular extension of functional domains. It has been shown in both preclinical and clinical studies that affibody molecules are safe, efficacious, and valuable alternatives to antibodies for specific targeting in the context of in vivo diagnostics and therapy. Here, we provide a general background of affibody molecules, give examples of reported applications, and briefly summarize the methodology for affibody generation.




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Geographic inequalities in need and provision of social prescribing link workers a retrospective study in primary care

BackgroundLong-term health conditions are major challenges for care systems. Social prescribing link workers have been introduced via primary care networks (PCNs) across England since 2019 to address the wider determinants of health by connecting individuals to activities, groups, or services within their local community.AimTo assess whether the rollout of social prescribing link workers was in areas with the highest need.Design and settingA retrospective study of social prescribing link workers in England from 2019 to 2023.MethodWorkforce, population, survey, and area-level data at the PCN-level from April 2020 to October 2023 were combined. Population need before the rollout of link workers was measured using reported lack of support from local services in the 2019 General Practice Patient Survey. To assess if rollout reflected need, linear regression was used to relate provision of link workers (measured by full-time equivalent [FTE] per 10 000 patients) in each quarter to population need for support.ResultsPopulations in urban, more deprived areas and with higher proportions of people from minority ethnic groups had the highest reported lack of support. Geographically these were in the North West and London. Initially, there was no association between need and provision; then from July 2022, this became negative and significant. By October 2023, a 10-percentage point higher need for support was associated with a 0.035 (95% confidence interval = −0.634 to −0.066) lower FTE per 10 000 patients.ConclusionRollout of link workers has not been sufficiently targeted at areas with the highest need. Future deployments should be targeted at those areas.




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Information needs for GPs on type 2 diabetes in Western countries: a systematic review

BackgroundMost people with type 2 diabetes receive treatment in primary care by GPs who are not specialised in diabetes. Thus, it is important to uncover the most essential information needs regarding type 2 diabetes in general practice.AimTo identify information needs related to type 2 diabetes for GPs.Design and settingSystematic review focused on literature relating to Western countries.MethodMEDLINE, Embase, PsycInfo and CINAHL were searched from inception to January 2024. Two researchers conducted the selection process, and citation searches were performed to identify any relevant articles missed by the database search. Quality appraisal was conducted with the Mixed Methods Appraisal Tool. Meaning units were coded individually, grouped into categories, and then studies were summarised within the context of these categories using narrative synthesis. An evidence map was created to highlight research gaps.ResultsThirty-nine included studies revealed eight main categories and 36 subcategories of information needs. Categories were organised into a comprehensive hierarchical model of information needs, suggesting ‘Knowledge of guidelines’ and ‘Reasons for referral’ as general information needs alongside more specific needs on ‘Medication’, ‘Management’, ‘Complications’, ‘Diagnosis’, ‘Risk factors’, and ‘Screening for diabetes’. The evidence map provides readers with the opportunity to explore the characteristics of the included studies in detail.ConclusionThis systematic review provides GPs, policymakers, and researchers with a hierarchical model of information and educational needs for GPs, and an evidence map showing gaps in the current literature. Information needs about clinical guidelines and reasons for referral to specialised care overlapped with needs for more specific information.




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Collaborative discussions between GPs and pharmacists to optimise patient medication: a qualitative study within a UK primary care clinical trial

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.




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Do I know you? (well enough to complete your multisource feedback &#x2026; )




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Seeing the timber and the trees




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Deep End Kawasaki/Yokohama: A New Challenge for GPs in Deprived Areas in Japan [Innovations in Primary Care]




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A Few Doctors Will See Some of You: The Critical Role of Underrepresented in Medicine (URiM) Family Physicians in the Care of Medicaid Beneficiaries [Original Research]

PURPOSE

Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity.

METHODS

This descriptive cross-sectional study used 2016 Medicaid claims data from the Transformed Medicaid Statistical Information System and from 2016-2017 American Board of Family Medicine certification questionnaire responses to examine the diversity and Medicaid participation of FPs. We explored the diversity of FP Medicaid patient panels and whether they saw ≥150 beneficiaries in 2016. Using logistic regression models, we controlled for FP demographics, practice characteristics, and characteristics of the communities in which they practiced.

RESULTS

Of 13,096 FPs, Latine, Hispanic, or of Spanish Origin (LHS) FPs and non-LHS Black FPs saw more Medicaid beneficiaries compared with non-LHS White and non-LHS Asian FPs. The patient panels of URiM FPs had a much greater proportion of Medicaid beneficiaries from racial and ethnic minority groups. Overall, non-LHS Black and LHS FPs had greater odds of seeing ≥150 Medicaid beneficiaries in 2016.

CONCLUSIONS

These findings clearly show the critical role URiM FPs play in caring for Medicaid beneficiaries, suggesting physician race and ethnicity are correlated with Medicaid participation. Diversity in the health care workforce is essential for addressing racial health inequities. Policies need to address problems in pathways to medical education, including failures to recruit, nurture, and retain URiM students.




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Osteoporosis Canada guideline on screening for men likely low value [Letters]




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Management of central sleep apnoea: a review of non-hypercapnic causes

Central sleep apnoea (CSA) is characterised by recurrent episodes of airway cessation or reduction in the absence of respiratory effort. Although CSA is less common than obstructive sleep apnoea, it shares similar symptoms. CSA can be secondary to various medical conditions, high altitude and medication exposure. CSA can also emerge during obstructive sleep apnoea therapy. There are a range of treatment options and selecting the right therapy requires an understanding of the pathophysiology of CSA. This review explores the aetiology, pathophysiology and clinical management of non-hypercapnic CSA.




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You Have Less Than a Week to File a Claim for Cash App’s $2,500 Payouts



The deadline to claim part of the $15 million Cash App settlement is November 18. Here's what to know.



  • Privacy and Security

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Even Exxon’s CEO Doesn’t Want Trump to Pull Out of the Paris Climate Agreement



The head of one of the world's largest oil companies has had it with government flip-flopping.




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ExpressVPN Has Never Been This Cheap: This Trick Can Save You 61% on This VPN



This is not a joke, the subscription to ExpressVPN is at an unprecedented price. We'll tell you everything you need to know so you don't miss out on its Black Friday offer.






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Column: Why reporting from South Sudan is so difficult — and critically needed

Simona Foltyn walks down a mountain slope shortly after crossing into South Sudan. Photo by Jason Patinkin

In August, fellow reporter Jason Patinkin and I crossed on foot from northern Uganda into rebel-held South Sudan. Over the course of four days, we walked more than 40 miles through the bush, escorted by rebel soldiers, to shed light on one of the world’s most underreported conflicts.

Reporting on South Sudan’s war, which began in 2013, has always been a challenge due to the risk and logistical hurdles associated with accessing remote areas where fighting takes place. But over the past year, covering the war and its humanitarian fallout has become particularly difficult. Since the beginning of this year, South Sudan’s government has banned at least 20 foreign journalists in an apparent effort to silence reporters who had a track record of critically reporting on the government.

The war has had a devastating impact on South Sudanese communities, but much of it has remained out of the limelight of international media.

This systematic crackdown on the foreign press (South Sudanese journalists have long risked imprisonment and death for doing their work) coincided with two important developments. In November 2016, the United Nations warned that the violence being committed against civilians in the southern region of Equatoria risked spiraling into genocide. Then, in February, the UN declared a man-made famine, warning that 100,000 people were at risk of starving to death as a result of civil war.

Journalists seeking to cover these events were left with two equally unsavory options: self-censorship or a risky trip to rebel-held parts of the country. Only a handful of journalists have attempted the latter since fighting escalated in July last year. For us, this was our second embed with the rebels this year.

Martin Abucha (second from right) rests with his troops in rebel-held South Sudan. Photo by Jason Patinkin

We set off from a town in northern Uganda at five in the morning, bouncing along a bumpy dirt track towards the South Sudan border. Crammed into our four-wheel drive were rebel commander Martin Abucha, a dual American and South Sudanese citizen who we planned to profile for our PBS NewsHour Weekend segment, a couple of guides, and several duffle bags stuffed with our tents, sleeping bags, emergency medical kits and provisions to last us four days.

Just as the sun began to rise above a distant range of hills that we aimed to cross later that day, our car came to a halt in front of a stream. Because of the rainy reason, it carried more water than usual. It was time to disembark and start walking, or “footing,” as South Sudanese tend to call it.

We took off our shoes and waded through the stream’s chilly waters. This was the first of a many rivers we’d have to cross along the way, either on foot or in small flimsy canoes dug out from tree trunks. Each time, we dreaded the idea of falling in with our camera gear.

The first part of our journey in northern Uganda felt very much like a hike through a national park. Passing beautiful landscapes and idyllic farming villages, one could almost forget we were headed into a war zone — but we were about to get a reality check.

We had just crossed into South Sudan when out of nowhere, two dozen armed men popped out of the tall grass and surrounded us at gunpoint.

“Stop! Who are you and where are you going?” a soldier called out in Juba Arabic from his hideout no more than 20 yards away, pointing his AK47 at us. Another one next to him had a rocket-propelled grenade propped on his shoulder, also unequivocally aiming it in our direction.

Instinctively, we threw our hands in the air and exchanged a baffled glance. Had we accidentally bumped into government soldiers? Or perhaps we had come onto the “wrong” rebels? Abucha’s group, called the Sudan People’s Liberation Army In Opposition, is the biggest but not the only armed group in Equatoria, an area rife with rival militia and bandits who exploit the security vacuum left by war.

To our relief, and only after Abucha answered a series of questions, this routine security check quickly gave way to a warm welcome. The platoon would be our escort for the next four days as we trekked to their base and to Loa, Abucha’s hometown.

Keeping up with the rebels was no easy task. Given the country’s pervasive lack of basic infrastructure, South Sudanese grow up walking for dozens of miles just to go about their daily lives. For sedentary Westerners, keeping the target pace of “two meters per second” (around five miles an hour) proved challenging amid 90-degree temperatures, all while filming and plowing our way through dense, itchy elephant grass.

The upside of the cumbersome terrain was that it kept us safe. During our four-day trip, we didn’t cross a single road, instead walking along a dizzying network of narrow bush paths the rebels seemed to know like the backs of their hands. An unwanted encounter with government troops, who tended to stick to roads and move around in vehicles as opposed to on foot, was highly unlikely.

The closest we got to government-controlled area was a visit to Loa, located just two kilometers away from a main road frequently patrolled by government soldiers. We couldn’t stay long, but the hour we spent on the ground offered us a glimpse into what villages must look like in many parts of Equatoria: burned mud huts, looted schools and clinics, fallow fields and – most strikingly – no civilians.

The war has had a devastating impact on South Sudanese communities like the one in Loa, but much of it has remained out of the limelight of international media. Our four-day venture into rebel-held South Sudan offered us a rare opportunity to report ground truths, and we are thankful for that.

The post Column: Why reporting from South Sudan is so difficult — and critically needed appeared first on PBS NewsHour.




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South Sudan civil war causes Africa’s worst refugee crisis

Watch Video | Listen to the Audio

The United Nations says South Sudan’s four-year-old civil war has left half of the nation’s population — 6 million people — in need of humanitarian aid. The conflict began when South Sudan’s army split between factions loyal to President Salva Kiir and former Vice President Riek Machar. The two men mobilized their respective tribes, the Dinka and the Nuer. The war has caused what is now one of the world’s worst refugee crises.

SIMONA FOLTYN: Civil war is emptying huge swaths of South Sudan. The violence has uprooted four million people, including two million who’ve fled to neighboring countries. In the last year, more than a million South Sudanese have poured into northern Uganda alone, crossing makeshift bridges like this one to flee fighting, hunger, and brutal attacks on civilians.

SEME LUPAI, REFUGEE: They started fighting very, very severely. So that made us to escape with our properties to this side.

SIMONA FOLTYN: When Seme Lupai’s family went to one of the refugee camps, initially, he stayed behind to look after the family’s most precious commodity — their cattle. He hid for a year to escape the violence. The refugees carry whatever they can salvage — mattresses, pots, clothes, notebooks — remnants of once peaceful lives turned upside down. At checkpoints, Ugandan soldiers search their belongings for weapons, before the refugees proceed to reception centers. After entering Uganda, the refugees sign in at small waystations. For many, it’s the first night spent in safety after walking for days to escape fighting. Levi Arike fled with his wife and four children.

LEVI ARIKE, REFUGEE: When the gunshots started, we laid under a tree with the whole family, because there was nowhere else to hide. We waited for the fighting to stop, and then we got up and started walking to Uganda.

SIMONA FOLTYN: Uganda now shoulders most of the burden of Africa’s biggest refugee crisis, managing a constellation of camps which require food, water, healthcare, and policing. At Imvepi Camp, now home to more than 120,000 South Sudanese, new arrivals receive vaccinations, hot meals, and basic items such as soap and plastic tarps to build a house. The government also gives each refugee family a small plot of land, about a twentieth of an acre, where they can build a tent shelter and grow crops to eat or sell. But the land often proves too rocky for farming.

SIMONA FOLTYN, IMVEPI REFUGEE CAMP, NORTHERN UGANDA: After completing the registration process, the new arrivals will receive their plot, to start a new life as refugees in Uganda. While they are safe here, there are many challenges ahead, not least processing the trauma of what they experienced back home.

This woman, who we’ll call “Agnes,” agreed to tell us about her harrowing experience. She says four government soldiers from President Salva Kiir’s Dinka tribe stopped her as she was fleeing South Sudan and raped her right in front of her family.

AGNES (translated to English): When they started raping me, they told me not to raise alarm, otherwise they would shoot me. Still when I’m sleeping, I’m dreaming of the Dinka, that they are coming to rape me again.

SIMONA FOLTYN: How often do you have those dreams?

AGNES: Daily, every time I lie down, those dreams come.

SIMONA FOLTYN: A recent Human Rights Watch report on South Sudan found “…a clear pattern of government forces unlawfully targeting civilians for killings, rapes, torture…and destruction of property..” The victims are from ethnic groups suspected to support the rebels.

AGNES: They are doing it, because they know very well that those soldiers are our brothers. So they do it to punish them..

SIMONA FOLTYN: Although the rebels, known as the Sudan People’s Liberation Army In Opposition, purport to protect local communities, there are also reports of their fighters assaulting civilians near the Ugandan border. Josephine Yanya told us she didn’t feel safe in the presence of either side’s soldiers. Her family and neighbors fled their village after government soldiers killed her uncle.

They hid in the mountains only to find themselves under attack again, this time by opposition fighters from the Nuer tribe loyal to former vice president Riek Machar. Yanya says ethnic Nuer soldiers from the SPLA-IO rebel group raped a member of her group and stole her father’s’ cattle.

JOSEPHINE YANYA (translated to English): Before we were thinking that the rebels would protect us, but if they are lacking food, they just come and take things by force.

SIMONA FOLTYN: With nowhere left to hide, Yanya fled to Uganda with her son.
But instead of finding a place to rebuild their lives, they are in limbo. And aid groups don’t have enough food to distribute.

JOSEPHINE YANYA (translated to English):We are getting small food rations. I know it won’t be enough even for one month.

SIMONA FOLTYN: According to the United Nations, the international community has given less than a-third of the $1.4 billion dollars needed for the refugee response in South Sudan’s neighboring countries. These refugees foresee more hardship and have no idea when they might return home.

JOSEPHINE YANYA (translated to English): I’m always praying for peace in South Sudan, and until then, I’ll just stay here.

The post South Sudan civil war causes Africa’s worst refugee crisis appeared first on PBS NewsHour.




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Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence

Watch Video | Listen to the Audio

HARI SREENIVASAN: The desire of the Kurds along Iraq’s northern border to govern themselves is receiving more resistance from Iraq’s central government. Iraqi army forces are demanding Kurdish troops withdraw from oil fields and military bases around Kirkuk, a city in the Kurdistan region that voted for independence last month. Kirkuk also has 10% of Iraq’s known oil reserves. Washington Post’s Loveday Morris is in Baghdad covering this standoff joins me now via Skype. First of all the significance of this. Why is it so important?

LOVEDAY MORRIS: There’s been a longtime conflict between Baghdad and Kurdistan over these disputed territories. Most significant of which is Kirkuk because of the oil reserves. But the referendum last month has really sharpened these disputes because you have Baghdad opposing independence and so it feels like they have to restate its territorial claims these areas. So that’s why we’re seeing a lot of tension right now.

HARI SREENIVASAN: And just to give people a little bit of a brief timeline – Iraqi forces control this area for a while and then in June ISIS took over the area and now it’s kind of back in Kurdish hands?

LOVEDAY MORRIS: Right. So in June 2014 Iraq lost control of a lot of the areas and we have this huge collapse in the face of an ISIS offensive. Over 100,000 soldiers fled and Kurdish forces moved in some of these areas – some of them maybe took from ISIS and others just moved into into the vacuum. And so Iraqi forces have been in these areas since June 2014. And that’s their main demand that they return to the areas.

HARI SREENIVASAN: What’s the likelihood that this standoff right now turns violent? Into some sort of a civil war?

LOVEDAY MORRIS:: I think at this point both sides don’t want violence. Al-Abadi, the prime minister, is really trying to defuse the situation by saying there’s going to be no military attack. But at the same time there is this buildup of forces so that I think they are trying to, in a way, intimidate the Kurds to withdraw from some areas but they don’t want to see a fight per say. But in this really tense situation there can be a small spark and things can turn violent quite easily.

HARI SREENIVASAN: Thank you.

The post Iraqi, Kurdish forces in standoff, weeks after Kurdish vote for independence appeared first on PBS NewsHour.




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U.S., Japan agree to maximize diplomatic pressure on North Korea

Monitor in Tokyo shows news of North Korea firing a ballistic missile on July 4. File photo by Toru Hanai/Reuters

TOKYO — U.S. and Japanese diplomats agreed Tuesday to maximize pressure on North Korea to resolve tensions over its nuclear program, while citing the need to be prepared for the worst if diplomacy fails.

U.S. Deputy Secretary of State John Sullivan, after meeting his Japanese counterpart, Shinsuke Sugiyama, told reporters that the focus at the State Department is still on diplomacy to solve the problem and eventually denuclearize the Korean Peninsula.

“We must, however, with our allies in Japan and South Korea and elsewhere, be prepared for the worst should diplomacy fail,” he said. The U.S. must be prepared to defend itself and its allies, he said.

Sugiyama, briefing reporters separately, reiterated Japan’s support for President Donald Trump’s policy of keeping all options open, but stressed the need for a diplomatic solution by bolstering cooperation among Japan, U.S. and South Korea, as well as via cooperation with China and Russia.

The two diplomats will join their South Korean counterpart in Seoul for further talks Wednesday on North Korea.

READ MORE: Rex Tillerson says continue diplomacy with North Korea ‘until first bomb drops’

The talks come as the U.S. and South Korea hold joint naval drills this week. They regularly conduct joint exercises, though North Korea condemns them as an invasion rehearsal.

North Korea’s deputy U.N. ambassador warned on Monday that the situation on the peninsula “has reached the touch-and-go point and a nuclear war may break out any moment.”

Kim In Ryong told the U.N. General Assembly’s disarmament committee that North Korea has been subjected to a direct nuclear threat from the United States and has the right to possess nuclear weapons in self-defense.

He pointed to military exercises and what he called a U.S. plan to stage a “secret operation aimed at the removal of our supreme leadership.”

Kim’s speech follows increasingly tough U.N. sanctions. Russian President Vladimir Putin said his country is curtailing economic, scientific and other ties with North Korea in line with U.N. sanctions, and the European Union announced new sanctions as well.

The post U.S., Japan agree to maximize diplomatic pressure on North Korea appeared first on PBS NewsHour.




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WATCH: Trump and Greek prime minister hold joint news conference


Watch President Donald Trump and the Greek prime minister’s joint news conference in the player above.

WASHINGTON — President Donald Trump says the U.S. stands with Greece as they recover from their economic crisis. He is speaking with Prime Minister Alexis Tsipras at the White House in a joint news conference.

The U.S. president says the two leaders have discussed defense, energy, commerce and trade.

Trump is praising Greece for its defense spending under NATO and is noting a potential sale to Greece to upgrade its F-16 aircraft, which he says would be worth up to $2.4 billion and generate thousands of U.S. jobs.

Tsipras says his country has made economic strides and is “leaving behind the economic model that led to the crisis.” He says Greece’s relationship with the U.S. is “more important than ever.”

The post WATCH: Trump and Greek prime minister hold joint news conference appeared first on PBS NewsHour.




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As Rohingya refugees continue to flee from persecution, here’s how you can help

A Rohingya refugee girl poses with a chicken at the Balukhali refugee camp near Cox’s Bazar in Bangladesh. Photo by Jorge Silva/Reuters

More than 500,000 Rohingya Muslims have fled their homes since August to escape systematic violence at the hands of government soldiers in Myanmar. The U.N. has called the actions taken by Myanmar forces against the group “a textbook example of ethnic cleansing.”

A report released by Amnesty International on Wednesday documents widespread rape, killings and burnings of Rohingya across the Rakhine State in Myanmar. The report includes extensive interviews of Rohingya refugees who tell stories of live burnings, sexual violence and mass shootings at the hands of soldiers.

To escape persecution, Rohingya refugees are fleeing in droves to neighboring Bangladesh, a country described by some as a reluctant host for the thousands of refugees behind its borders. Conditions within Bangladesh show refugee camps beyond capacity, as organizations struggle to keep up with humanitarian aid.

Find out more: Rohingya Muslims have been denied citizenship in Myanmar since 1982, though they’ve lived in the area since the 12th century. They are not considered one of the country’s official ethnic groups. As such, their lack of official identity bars them from government services and travel.

Officials from Myanmar, a majority Buddhist state, claim Rohingya are actually immigrants from Bangladesh to justify their exclusion of the group. This most recent burst of violence comes from Myanmar’s crackdown following clashes with the Arakan Rohingya Salvation Army (ARSA). After the government declared ARSA a terrorist organization, the retaliation escalated into hundreds of Rohingya villages.

Where to give: BRAC, a top-ranked NGO based out of Bangladesh, is scaling up humanitarian efforts for clean water, health, sanitation and child care for refugees from Myanmar. You can learn more about their efforts here.

An emergency appeal was made by the Disasters Emergency Committee for immediate crisis relief funds. DEC distributes funds to 13 member aid organizations.
UNHCR, UNICEF and Save the Children have donation pages dedicated to the crisis, as does the International Rescue Committee. CNN’s Public Good page provides a user-friendly resource to find NGOs that match your giving goals.

To give to starvation relief, try Action Against Hunger or the World Food Programme.

Be sure to research organizations receiving your financial contributions, not only to find the best organization aligned with your goals, but also to avoid potential scams. For the latest information on aid organizations and charities, visit GuideStar or Charity Navigator to ensure your donations are going in the right direction.

The post As Rohingya refugees continue to flee from persecution, here’s how you can help appeared first on PBS NewsHour.




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Eels director ready for fight

Paul Garrard has no plans to walk away but has urged Geoff Gerard to resign if he has lost his desire to fight.