BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

BACKGROUND AND PURPOSE:

Periprocedural intracranial hemorrhage is one of common complications after stent placement for symptomatic intracranial atherosclerotic stenosis. This study was conducted to demonstrate predictors and long-term outcomes of periprocedural intracranial hemorrhage after stent placement for symptomatic intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE:

Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High-resolution 4D MR flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MR flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphologic proxy parameters for aneurysm instability.

SUMMARY:

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

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.

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.

Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for biopanning using multiple display methods. This protocol describes selection from affibody libraries using display on Staphylococcus carnosus. Display of affibodies on staphylococci is very efficient and straightforward because of the single cell membrane and the use of a construct with a constitutive promoter. The workflow involves display of affibody libraries on the surface of S. carnosus cells, followed by screening and selection of binders using fluorescence-activated cell sorting (FACS). The transformation of DNA libraries into S. carnosus is less efficient and more complicated than for Escherichia coli. Because of this, staphylococcal display is suitable for affinity maturation or other protein-engineering efforts that are not dependent on very high diversity, and thus magnetic-activated cell sorting (MACS) is often not required before FACS. However, MACS is an option, and MACS procedures used for E. coli can easily be adapted for use in S. carnosus if needed.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 10¹¹ can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <10⁷ cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library. This is then followed by amplification of the library, which can then be used for biopanning using multiple methods. This protocol describes amplification of affibody libraries, followed by biopanning using phage display and analysis of the selection output. The general procedure is mainly for selection of first-generation affibody molecules from large naive (unbiased) libraries, typically yielding affibody hits with affinities in the low nanomolar range. For selection from affinity maturation libraries with the aim of isolating variants of even higher affinities, the procedure is similar, but parameters such as target concentration and washing are adjusted to achieve the proper stringency.

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.

The positional preference of an animal can be very informative regarding the choices it makes about how to interact with its environment. The fruit fly Drosophila melanogaster has been used as a robust system for examining neurobiological mechanisms underlying behavior. Fruit fly positional preference can be gathered from TriKinetics Drosophila activity monitors (DAMs), which contain four infrared beams, allowing for tracking the position of individual flies along the length of a tube. Here, we describe a method for using DAM5Ms to examine food preference. Specifically, we show an example in which circadian changes in food preference are compared between different Drosophila species. More information about the evolution of behavior can be gathered by measuring feeding preference relative to time of day. Noni, fruit from Morinda citrifolia, contains octanoic acid, a chemical toxic to many species of Drosophila. D. melanogaster and D. simulans, both food generalists, show high sensitivity to octanoic acid, whereas D. sechellia, a specialist, can tolerate high concentrations. When two different food substrates are provided at each end of a tube, food preference can be inferred at various times of the day, using the sleep and circadian analysis MATLAB program (SCAMP) to extract and analyze positional data from DAM5Ms. Data gathered from these analyses can be used to compare avoidance or attraction to nutrients, tastants, or odors between species and genotypes or after specific different treatments. Additionally, such data can be examined as a function of time of day.

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.

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.

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.

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

Practicing family medicine is really hard; the emotional toll of sharing patients’ distress, vulnerability, and trauma can build up and become overwhelming. A family physician experienced such a moment during one particularly complex morning. Feeling nearly ready to walk out of patient care, she reached out to the team nurse, who helped her get through the moment and re-engage with the waiting patients. Sharing vulnerability in the moment, and later reflecting and deciding to write about it shows the power of prioritizing teamwork in practice.

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

Patient expectations of receiving antibiotics for common symptoms can trigger unnecessary use. We conducted a survey (n = 564) between January 2020 to June 2021 in public and private primary care clinics in Texas to study the prevalence and predictors of patients’ antibiotic expectations for common symptoms/illnesses. We surveyed Black patients (33%) and Hispanic/Latine patients (47%), and over 93% expected to receive an antibiotic for at least 1 of the 5 pre-defined symptoms/illnesses. Public clinic patients were nearly twice as likely to expect antibiotics for sore throat, diarrhea, and cold/flu than private clinic patients. Lack of knowledge of potential risks of antibiotic use was associated with increased antibiotic expectations for diarrhea (odds ratio [OR] = 1.6; 95% CI, 1.1-2.4) and cold/flu symptoms (OR = 2.9; 95% CI, 2.0-4.4). Lower education and inadequate health literacy were predictors of antibiotic expectations for diarrhea. Future antibiotic stewardship interventions should tailor patient education materials to include information on antibiotic risks and guidance on appropriate antibiotic indications.

PURPOSE

The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients.

BACKGROUND

For many patients with post–COVID-19 condition (long COVID), primary care is the first point of interaction with the health care system. In principle, primary care is well situated to manage long COVID. Beyond expressions of disempowerment, however, the patient’s perspective regarding the quality of long COVID care is lacking. Therefore, this study aimed to analyze the expectations and experiences of primary care patients seeking treatment for long COVID.

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene–projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene–projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene–projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene–projection relationship.

There is conflicting evidence regarding the use of steroids in severe community-acquired pneumonia (CAP), with previous randomised controlled trials limited by small sample sizes. ESCAPe and CAPE COD are two recently published large trials on steroids in severe CAP. ESCAPe assessed the initiation of methylprednisolone within 72–96 h of hospital admission, while CAPE COD studied the use of hydrocortisone within 24 h of the development of severe CAP. ESCAPe did not show any differences in all-cause 60-day mortality or any of its secondary outcomes. CAPE COD showed that hydrocortisone improved all-cause 28-day mortality and reduced the risk of intubation or vasopressor-dependent shock. Important differences between the trials included the steroid regimens used, timing of steroid administration and baseline characteristics, with more diabetic patients included in ESCAPe. The results of CAPE COD support the initiation of hydrocortisone within 24 h of developing severe CAP, but more research is needed to evaluate long-term outcomes and optimum dosing regimens for steroids in severe CAP.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Bone marrow transplantation, now often known as haematopoietic stem cell transplantation (HSCT), is a complex choreographed procedure used to treat both acquired and inherited disorders of the bone marrow. It has proven invaluable as therapy for haematological and immunological disorders, and more recently in the treatment of metabolic and enzyme disorders. As the number of performed transplants grows annually, and with patients enjoying improved survival, a knowledge of both early and late complications of HSCT is essential for respiratory trainees and physicians in practice. This article highlights the spectrum of respiratory complications, both infectious and non-infectious, the timeline of their likely occurrence, and the approaches used for diagnosis and treatment, keeping in mind that more than one entity may occur simultaneously. As respiratory issues are often a leading cause of short- and long-term morbidity, consideration of a combined haematology/respiratory clinic may prove useful in this patient population.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.

Writer-director partners Scott Beck and Bryan Woods dive into the biggest spoilers of their new Hugh Grant thriller.

The driverless vehicles still can't take L.A.'s notorious highways.

There has been fallout. Speaker Nathan Cooper is said to have decreed guests will never again be seated inside the legislative chamber.

The post Edmonton activist protests climate crisis with demonstration in AB legislature appeared first on rabble.ca.

At least 231 people were killed and hundreds more wounded after a massive truck bomb on Saturday struck Somalia’s capital city of Mogadishu.

The Somali government has blamed the al-Qaida-linked militant group al-Shabab for the attack, and called it the deadliest ever to hit the nation.

The blast took place outside the Safari Hotel, where rescue workers dug through the rubble of collapsed buildings overnight in search of survivors. Witnesses described a devastating scene with large-scale carnage, as doctors worked feverishly to attend to the dead and injured, many badly burned.

“The hospital is overwhelmed by both dead and wounded,” Dr. Mohamed Yusuf, the director of Medina hospital located near the blast, told the Associated Press. “We also received people whose limbs were cut away by the bomb. This is really horrendous, unlike any other time in the past.”

Photos and videos of the bombing, which took place on a busy street near a section of the city housing foreign embassies, showed collapsed walls, twisted metal, and sporadic fires spewing smoke. The Qatari government said its embassy was “severely damaged” in the strike.

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Family members searched through the wreckage and waited at local hospitals with the hopes of finding relatives who survived the bombing.

Somali President Mohamed Abdullahi Mohamed announced three days of mourning. The attacks received international condemnation, including from the United States.

The post Hundreds dead after massive truck bomb strikes Mogadishu appeared first on PBS NewsHour.

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JUDY WOODRUFF: And in the day’s other news: More than 300 people are now confirmed dead after Saturday’s massive truck bombing in Somalia, one of the world’s worst attacks in years.

Nearly 400 more were wounded. The government blamed the al-Qaida-linked Al-Shabaab group. Rescue crews today searched for survivors at the scene of the bombing, a crowded street in the capital, Mogadishu. With dozens still missing, officials say they expect the death toll to rise.

OSMAN LIBAH IBRAHIM, Deputy Minister for Natural Resources, Somalia (through interpreter): More bodies are gradually being found and removed from the rubble. There are other people who are under the rubble. We have heard them as they scream for help. My biggest worry is that even the wounded are succumbing to their injuries.

JUDY WOODRUFF: The attack happened two days after Somalia’s defense minister and army chief resigned for undisclosed reasons.

There’s been yet another shift to the right in European politics; 31-year-old conservative Sebastian Kurz, Austria’s foreign minister, is set to become that country’s next leader. But he’s short of a majority in Parliament and will likely form a coalition with the far-right Freedom Party. It was founded by ex-Nazis in the 1950s.

Kurz has called for the European Union to focus more on internal trade and securing borders. He celebrated in Vienna.

SEBASTIAN KURZ, Austrian People’s Party (through interpreter): I have a big request for you. Use today to celebrate. You all have earned it through hard work and dedication. At the same time, I need to tell you that tomorrow the work starts. We didn’t just run to win the elections. We did so to bring Austria back to the top. We ran in this election to achieve real change.

JUDY WOODRUFF: A final result in the election is likely to be decided on Thursday.

Wildfires that broke out over the weekend in Portugal have killed at least 35 people, including a one-month-old infant. Today, more than 5,300 firefighters with some 1,600 vehicles were battling the fires, some of which officials say were started by arsonists. Wildfires have also left at least four people dead in neighboring Spain.

Army Sergeant Bowe Bergdahl pleaded guilty today to desertion and misbehavior before the enemy. He was captured by the Taliban in 2009, after leaving his post in Afghanistan. It prompted an intense search and a prisoner swap. Bergdahl appeared before a military judge in Fort Bragg, North Carolina, today. The 31-year-old could be sentenced to life in prison. He said his actions were very inexcusable, adding he didn’t — quote — “think there’d be any reason to pull off a crucial mission to look for one guy.”

The truck driver in deadly immigrant smuggling run has pleaded guilty in court. San Antonio police found at least 39 immigrants, 10 of whom died, packed into a sweltering semi-trailer last year and died. The driver, James Matthew Bradley Jr., pleaded to conspiracy and transporting immigrants, resulting in death. He faces now up to life in prison.

A New Jersey man has been convicted of planting two pressure-cooker bombs on New York City streets last year. Ahmed Khan Rahimi faces a maximum sentence of life in prison for charges including using a weapon of mass destruction. One of the bombs exploded in Manhattan’s Chelsea neighborhood, wounding 30. The second didn’t detonate. Officials said Rahimi was inspired by ISIS and al-Qaida.

JOHN MILLER, Deputy Commissioner, NYPD Intelligence & Counterterrorism: Ahmed Khan Rahimi learned a lesson which we keep reminding people of. This is the wrong place to try and carry out an act of terrorism. Witnesses will come forward, evidence will be developed, arrests will be made, prosecutions will be brought forth, and they will be successful.

JUDY WOODRUFF: Prosecutors said Rahimi also planted a pipe bomb in Seaside Heights, New Jersey, but no one was injured.

Colin Kaepernick has filed a grievance against the national football league. The former San Francisco 49ers quarterback says that he remains unsigned due to collusion by team owners over his national anthem protests. Kaepernick sparked a debate when he kneeled during the anthem last year, protesting police mistreatment of African-Americans.

On Wall Street today, the Dow Jones industrial average gained 85 points to close at 22957. The Nasdaq rose 18. And the S&P 500 added four.

It was a milestone day in the world of astronomy. For the first time, researchers say they have detected gravitational waves with a flash of light from the same cosmic event. The dual observation supports Albert Einstein’s general theory of relativity. The ripples in space and the light burst were caused by the collision of two neutron stars. They were first detected in August.

The post News Wrap: Dozens missing after deadly Mogadishu truck bombing appeared first on PBS NewsHour.

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HARI SREENIVASAN: But first: The de facto capital of the Islamic State, Raqqa, in Syria fell yesterday to U.S.-backed forces.

However, the largest city the militants once held was Mosul in Iraq. They were ousted from it in July after a brutal 10-month-long fight that killed thousands.

Now a new major task: finding and destroying the ISIS mines, booby-traps and bombs that litter the city.

Special correspondent Marcia Biggs reports from Iraq.

MARCIA BIGGS, Special Correspondent: It was once a center of learning for over 6,000 students of technology, agriculture, and medicine.

Today, Mosul Technical Institute’s classrooms are burnt to the ground, laboratories reduced to rubble, and books charred and shredded. It’s one of the city’s five universities ravaged by the Islamic State and the battle to oust it.

Now that the battle is over, a new danger looms, the trail of land mines and booby-traps left by ISIS.

So this is the wire, and this is where it was buried.

CHRISTIAN, Team Leader, Janus Global Operations: Yes, they would cut the asphalt, and then they lay the wire in and put the main charge here.

MARCIA BIGGS: We spent the day with Christian, a team leader from Janus Global, a security and risk management firm hired by the U.S. government to sweep and clear major areas of unexploded ordnance and mines.

He’s not allowed to show his face or use his last name, for security reasons.

CHRISTIAN: There’s actually two more on that road before we get to the target building that have to be excavated and/or rendered safe.

MARCIA BIGGS: So, the first building you have to clear, you have got to get rid of the IEDs on the road to that building?

CHRISTIAN: Yes.

MARCIA BIGGS: It’s a long process.

CHRISTIAN: It is, but that’s what makes it interesting.

MARCIA BIGGS: The United States has sunk $30 million this year into clearing former ISIS territories all over Northern Iraq. Under this program, Janus has already cleared 727 buildings, removing 3,000 IEDs, which they say ISIS was producing on assembly lines at an industrial scale.

But State Department officials and experts say the number of unexploded ordnance in Mosul itself is unprecedented.

What’s your first line of attack, in terms of trying to clear Mosul?

CHRISTIAN: Our priority is more the community, rather than the individual, you know, infrastructure. You have got schools, power, sewer, water, so that the area can accept people back into it. And then, once this stabilization phase is over, we can move into the individual homes, so that they can be safer.

MARCIA BIGGS: Clearing Mosul is a process that they say could take years, even decades. So Janus is training local Iraqis to do the job, sending them out as a front-line search team, then investigating and removing any suspicious items themselves.

CHRISTIAN: We’re not going to be here the whole time, so when we — it’s our time to leave, they will have the capacity built from us, and the mentoring we have done, so that they can do it on their own.

MARCIA BIGGS: How are they doing?

CHRISTIAN: They’re — a lot of them are very apt to learn. They’re quick. They’re smart.

MARCIA BIGGS: Fawzi al Nabdi is the team leader for the Iraqi local partner. He’s cleared mines all over Iraq for the last six years.

CHRISTIAN: What you got?

FAWZI AL NABDI, Team Leader, Al Fahad Company (through interpreter): We are ready for this, because it’s my job and I love it. The Americans are here to complete our work and to help us. They have greater experience than we do. If we find any mines, we have to stop and they will investigate it and make a plan to remove it.

MARCIA BIGGS: But he says Mosul is the biggest project he has ever seen, and we’re told it could take at least a month to just get the campus cleared of mines. Only then can they start cleaning it up, so that students can resume classes, this itself a huge task.

ISIS fighters closed the university back in 2014, and used it as a military base. As coalition forces pounded ISIS targets, this seat of higher learning became a battleground.

Ghassan Alubaidy is the institute’s dean.

GHASSAN ALUBAIDY, Dean, Mosul Technical Institute (through interpreter): ISIS used our university to manufacture mines and bombs. For this reason, it was the target of airstrikes in the beginning. They struck the institute nine times, and they struck our workshops, too. Now we can’t use them.

MARCIA BIGGS: The former commander of coalition forces in Iraq, Lieutenant General Stephen Townsend, recently listed 81 locations where bombs were dropped, but had not yet exploded.

Facilities used to make weapons were often on the list of high-value targets for the coalition. So now those places are twice as likely to contain dangerous items.

So, this was once a workshop for electrical engineering students. You can still see the lab tables here. It was hit by an airstrike in 2015. Afterwards, members of the university staff found bomb-making instructions among the rubble. This was likely an ISIS bomb-making factory, and judging by the crater, a high-value target.

Despite the damage, Dean Alubaidy says he will hold classes this fall in alternate buildings, until the campus is ready. He’s expecting registration to be in the thousands, students who lost three years of education during the fighting and don’t want to lose another one.

GHASSAN ALUBAIDY (through interpreter): On our Facebook pages, we found a great number of students posting that they were full of encouragement to come back. For us, it was unbelievable. We couldn’t imagine it, to see how many students wanted to start again, how they were dreaming of the first day of classes, when they could sit in front of teachers again and start to live their lives again.

MARCIA BIGGS: Next door, Mosul University has already started classes. Students even volunteered to help in the cleanup.

But across the river, West Mosul was the site of ISIS’ last stand and bore the brunt of the battle. It’s densely packed Old City, with its flattened buildings, is a challenge for mine-sweeping.

FAWZI AL-NABDI (through interpreter): Most of the homes here were full of mines. And just here in front of us, a man with two kids came back to his home, and when he opened the door, the bomb killed him and his kids.

MARCIA BIGGS: Ahmed Younes fled back in early July with only the clothes on his back. Residents have been virtually banned from returning to his neighborhood on the outskirts of the Old City, but Ahmed said he got special permission, in order to retrieve some personal items.

AHMED YOUNES, Local Resident (through interpreter): We came on our own. We got permission to come, but they are not responsible if anything happens to us.

MARCIA BIGGS: Right now, there is no plan to begin clearing the Old City or even to determine how many mines there are. It is still out of bounds to anyone but the Iraqi security forces.

So the Janus team is focusing on progress in the rest of the city, building by building, bomb by bomb.

CHRISTIAN: Whoever made this device had a set goal. And to allow him to win, people get hurt. So you kind of compete against him to be better than him to take it out before it can do any harm.

MARCIA BIGGS: So, you feel like you’re winning the battle against ISIS?

CHRISTIAN: Yes, one IED at a time.

MARCIA BIGGS: For the PBS NewsHour, I’m Marcia Biggs in Mosul, Iraq.

HARI SREENIVASAN: Tune in later.

Frontline’s latest film, “Mosul,” was on the ground filming the fight as it unfolded street by street and house by house. That’s tonight on PBS.

The post The battle for Mosul is over, but this hidden ISIS danger could lurk for years appeared first on PBS NewsHour.

Legendary Tiger Maurice Rioli was posthumously inducted into the Australian Football Hall of Fame last night.

The Scotch whisky distiller has announced a major change

The flats are described as the first new homes on the Scottish town's High Street 'in living memory'

Motorists have been urged to plan ahead with a major bridge due to close for work is carried out.  

Health Secretary Neil Gray will address concerns around his use of a ministerial car to attend football games at Hampden.

Shetland Library and the National Library of Scotland have been praised for "providing optimist for the future."

The concierge team at The Balmoral have helped raise awareness for a special event to raise money for charity in memory of Scotland legend Doddie Weir.

The site, on the shores of a famous Scottish loch, has been acquired for a luxury lodge development

With many media events getting pushed back, the news is a little trim this week. But we still manage to pull together our basket of zany personalities for a podcast we hope brings a smile to your face.

The post RPG Cast – Episode 545: “Did You Infect My Game With Harvest Moon?” appeared first on RPGamer.

Join Anna Marie, Chris, Josh, and Kelley this week, as things get a little weirder than usual. A sticky soda fracas kicks off the show. Meanwhile, Kelley runs the news section for the first time, which is good since Chris stomps off after discovering this is definitely the worst timeline of them all. And don't forget, #JRPGJuly continues for one more week!

The post RPG Cast – Episode 551: “I Don’t Want the Moe Future” appeared first on RPGamer.

Jonathan Stringer joins this week and helps Major Tomcat recruit Kelley and Chris for a PC RPG. Chris will likely just hack the planet instead. Kelley, meanwhile, will tend to her cat's bad habits.

The post RPG Cast – Episode 554: “Cat Smoker Meow” appeared first on RPGamer.