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A different kind of Ramadan: Hong Kong Muslims observe fasting month at home, as pandemic measures halt mosque gatherings

It is about 7pm when Muslim community leader Raheel Ahmed, 57, gathers with his wife, two sons and daughter for a home-made meal of dates, rice and spicy curried chicken, salad, fresh fruit and juice.For this Hong Kong family of Pakistani origin, it is their first meal after fasting for more than 12 hours, as this is the Islamic holy month of Ramadan.The world’s 1.8 billion Muslims mark the month by abstaining from food or drink from sunrise to sunset, and gathering as a community in mosques to…




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Jobs first: Bolsonaro fires popular health expert

Few global leaders have done more than Bolsonaro to play down the pandemic, which has killed nearly 2000 Brazilians.




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Pandemic destroys US jobs as Germany urges unity

WASHINGTON: The coronavirus epidemic sent US jobless totals soaring to historic highs on Friday, increasing pressure on authorities to follow Europe in phasing out lockdown measures despite still climbing American death tolls.Germany, meanwhile, marked the anniversary of the end of World War II in...




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Will robots take our jobs? It’s an age-old question. -- by Jayant Menon

The discussions around the impact of artificial intelligence and its impact on jobs could result in improved skills and greater adaptations by the world’s work force.




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Pandemic destroys 20.5m US jobs in April in historic collapse

The coronavirus lockdown wiped out 20.5 million US jobs in April, destroying nearly all the positions created in the previous decade in the world's largest economy, the country's labour department reported on Friday.

The unprecedented collapse drove the unemployment rate to 14.7 per cent — well beyond the peak hit in late 2009 during the global financial crisis — from 4.4pc in March.

And job losses in March were worse than initially reported, falling 870,000 even though the business closures mostly happened in the second half of the month.

The plunge in non-farm payroll employment was the largest ever recorded since 1939, while the jobless rate was the highest and the biggest increase since 1948, the report said.

Employment fell sharply in all major industry sectors, with particularly heavy job losses in leisure and hospitality, the first sector hit and the one bearing the brunt of the impact of the lockdowns.

However, the labour department noted that the some workers were misclassified in the report as employed when they should have been counted as laid off.

Had they been listed properly, the unemployment rate would have been nearly five percentage points higher.

Meanwhile, US President Donald Trump downplayed unprecedented US job losses, saying they were not a surprise.

“It's fully expected, there's no surprise. Somebody said, 'oh look at this,'” he said on Fox News minutes after the labour department published the figures.

“I'll bring it back,” he said.




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Pandemic slams healthcare jobs

The steep plunge in U.S. payrolls caused by the pandemic also slammed the healthcare sector, as many workers in dentists' and doctors' offices lost their jobs. Fred Katayama reports.




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Tiny 2-billion-year-old fossil blobs may be the oldest complex cells

Fossils of single cells found in China are 2 billion years old, making them the oldest eukaryotic cells in the fossil record and possibly our distant relatives




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UK observes two-minute silence to commemorate VE Day 75th anniversary

Along with millions around the nation, Prince Charles held a two-minute silence outside his family's Balmoral estate, while military jets flew over the United Kingdom's four capitals, and 1940s-style tea parties plus singalongs were planned in homes.




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Why do so many people become obsessed with UFOs and aliens?

They Are Already Here: UFO culture and why we see saucers by Sarah Scoles tries to find out what's so appealing about hunting UFOs




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Pandemic slams healthcare jobs

The steep plunge in U.S. payrolls caused by the pandemic also slammed the healthcare sector, as many workers in dentists' and doctors' offices lost their jobs. Fred Katayama reports.




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Nose Jobs Make Women Look Years Younger, Robot Says

Title: Nose Jobs Make Women Look Years Younger, Robot Says
Category: Health News
Created: 1/28/2020 12:00:00 AM
Last Editorial Review: 1/28/2020 12:00:00 AM




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Direct Observation of the Dynamics of Single-Cell Metabolic Activity during Microbial Diauxic Growth

ABSTRACT

Population-level analyses are rapidly becoming inadequate to answer many of biomedical science and microbial ecology’s most pressing questions. The role of microbial populations within ecosystems and the evolutionary selective pressure on individuals depend fundamentally on the metabolic activity of single cells. Yet, many existing single-cell technologies provide only indirect evidence of metabolic specialization because they rely on correlations between transcription and phenotype established at the level of the population to infer activity. In this study, we take a top-down approach using isotope labels and secondary ion mass spectrometry to track the uptake of carbon and nitrogen atoms from different sources into biomass and directly observe dynamic changes in anabolic specialization at the level of single cells. We investigate the classic microbiological phenomenon of diauxic growth at the single-cell level in the model methylotroph Methylobacterium extorquens. In nature, this organism inhabits the phyllosphere, where it experiences diurnal changes in the available carbon substrates, necessitating an overhaul of central carbon metabolism. We show that the population exhibits a unimodal response to the changing availability of viable substrates, a conclusion that supports the canonical model but has thus far been supported by only indirect evidence. We anticipate that the ability to monitor the dynamics of anabolism in individual cells directly will have important applications across the fields of ecology, medicine, and biogeochemistry, especially where regulation downstream of transcription has the potential to manifest as heterogeneity that would be undetectable with other existing single-cell approaches.

IMPORTANCE Understanding how genetic information is realized as the behavior of individual cells is a long-term goal of biology but represents a significant technological challenge. In clonal microbial populations, variation in gene regulation is often interpreted as metabolic heterogeneity. This follows the central dogma of biology, in which information flows from DNA to RNA to protein and ultimately manifests as activity. At present, DNA and RNA can be characterized in single cells, but the abundance and activity of proteins cannot. Inferences about metabolic activity usually therefore rely on the assumption that transcription reflects activity. By tracking the atoms from which they build their biomass, we make direct observations of growth rate and substrate specialization in individual cells throughout a period of growth in a changing environment. This approach allows the flow of information from DNA to be constrained from the distal end of the regulatory cascade and will become an essential tool in the rapidly advancing field of single-cell metabolism.




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Obstructive sleep apnoea treatment and blood pressure: which phenotypes predict a response? A systematic review and meta-analysis

The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment.

The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of –2.09 (95% CI –2.78– –1.40) mmHg for systolic BP and –1.92 (95% CI –2.40– –1.43) mmHg for diastolic BP and –1.27 (95% CI –2.34– –0.20) mmHg for systolic BP and –1.11 (95% CI –1.82– –0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP –2.93 mmHg), with uncontrolled BP at baseline (systolic BP –4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP –7.57 mmHg).

Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.




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Inhaled Corticosteroid Treatment in Chronic Obstructive Pulmonary Disease (COPD): Boon or Bane?

Inhaled corticosteroid (ICS)–based therapy is often used for patients with chronic obstructive pulmonary disease (COPD). However, this approach is under scrutiny because of ICS overuse in patients for whom it is not recommended and because of concerns about adverse events, particularly pneumonia, with long-term ICS use. Evidence suggests ICS may be beneficial in specific patients, namely, those with high blood eosinophil counts (eg, ≥300 cells/µL) or who are at a high risk of exacerbations. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 ABCD assessment tool, these patients belong in group D. For these patients, recommended initial treatment includes ICS in combination with long-acting β2-agonists (LABAs) when blood eosinophil counts are ≥300 cells/µL or LABA + long-acting muscarinic antagonist (LAMA) when patients are highly symptomatic, that is, with greater dyspnea and/or exercise limitation. Follow-up treatments for patients with persistent dyspnea and/or exacerbations may include LABA + ICS, LABA + LAMA, or LABA + LAMA + ICS, with use of ICS being guided by blood eosinophil counts. In this review, differences in the inflammatory mechanism underlying COPD and asthma and the role of ICS treatment in COPD are summarized. Furthermore, findings from recent clinical trials where use of ICS-based dual or triple therapy in COPD was compared with LABA + LAMA therapy and trials in which ICS withdrawal was evaluated in patients with COPD are reviewed. Finally, a step-by-step guide for ICS withdrawal in patients who are unlikely to benefit from this treatment is proposed. A video of the author discussing the overall takeaway of the review article could be downloaded from the link provided: https://www.youtube.com/watch?v=Uq7Sr5jqPDI.




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The effects of elevated temperature and PCO2 on the energetics and haemolymph pH homeostasis of juveniles of the European lobster, Homarus gammarus [RESEARCH ARTICLE]

Daniel P. Small, Piero Calosi, Samuel P. S. Rastrick, Lucy M. Turner, Stephen Widdicombe, and John I. Spicer

Regulation of extracellular acid–base balance, while maintaining energy metabolism, is recognised as an important aspect when defining an organism's sensitivity to environmental changes. This study investigated the haemolymph buffering capacity and energy metabolism (oxygen consumption, haemolymph [l-lactate] and [protein]) in early benthic juveniles (carapace length <40 mm) of the European lobster, Homarus gammarus, exposed to elevated temperature and PCO2. At 13°C, H. gammarus juveniles were able to fully compensate for acid–base disturbances caused by the exposure to elevated seawater PCO2 at levels associated with ocean acidification and carbon dioxide capture and storage (CCS) leakage scenarios, via haemolymph [HCO3] regulation. However, metabolic rate remained constant and food consumption decreased under elevated PCO2, indicating reduced energy availability. Juveniles at 17°C showed no ability to actively compensate haemolymph pH, resulting in decreased haemolymph pH particularly under CCS conditions. Early benthic juvenile lobsters at 17°C were not able to increase energy intake to offset increased energy demand and therefore appear to be unable to respond to acid–base disturbances due to increased PCO2 at elevated temperature. Analysis of haemolymph metabolites suggests that, even under control conditions, juveniles were energetically limited. They exhibited high haemolymph [l-lactate], indicating recourse to anaerobic metabolism. Low haemolymph [protein] was linked to minimal non-bicarbonate buffering and reduced oxygen transport capacity. We discuss these results in the context of potential impacts of ongoing ocean change and CCS leakage scenarios on the development of juvenile H. gammarus and future lobster populations and stocks.




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Body temperature stability observed in the whale sharks, the world's largest fish [RESEARCH ARTICLE]

Itsumi Nakamura, Rui Matsumoto, and Katsufumi Sato

It is generally assumed that the body temperature of large animals is less likely to change due to their large body size, resulting in a high thermal inertia and a smaller surface area to volume ratio. The goal of this study was to investigate the stability of body temperature in large fish using data from field experiments. We measured the muscle temperatures of free-ranging whale sharks (Rhincodon typus), the largest extant fish globally, and investigated their ectothermic physiology and the stability of their body temperatures. The measured muscle temperature of the whale sharks changed substantially more slowly than the water temperature fluctuations associated with vertical movements, and the whole-body heat-transfer coefficients (HTC) of whale sharks estimated using heat-budget models were lower than those of any other fish species measured to date. The heat-budget models also showed that internal heat production does not contribute to changes in muscle temperature. A comparative analysis showed that the HTC at cooling in various fish species including both ectothermic and endothermic species ranging from 10–4 to 103 kg was proportional to body mass–0.63. This allometry was present regardless of whether the fish were ectothermic or endothermic, and was an extension of the relationship observed in previous studies on small fish. Thus, large fish have the advantage of body temperature stability while moving in environments with large temperature variations. Our results suggest that the large body size of whale sharks aids in preventing a decrease in body temperature during deep excursions to more than 1000 m depths without high metabolic costs of producing heat.




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The Timed Inspiratory Effort Index as a Weaning Predictor: Analysis of Intra- and Interobserver Reproducibility

BACKGROUND:Prolonged ventilatory weaning may expose patients to unnecessary discomfort, increase the risk of complications, and raise the costs of hospital treatment. In this scenario, indexes that reliably predict successful liberation can be helpful.OBJECTIVE:To evaluate the intra- and interobserver reproducibility of the timed inspiratory effort index as a weaning predictor.METHODS:This prospective observational study included subjects judged as able to start liberation from mechanical ventilation. For the intra-observer analysis, the same investigator performed 2 measurements in each selected patient with an interval of 30 min a rest. For interobserver analysis, 2 measurements were obtained in another sample of subjects, also with an interval of 30 min rest, but each of one performed by a different investigator. The Bland-Altman diagram, the coefficient concordance of kappa, and the Pearson correlation coefficient were used to compare the measurements. The performance of the timed inspiratory effort index was assessed by receiver operating characteristic curves. Values of P < .05 were considered significant.RESULTS:We selected 113 subjects (43 males; mean ± SD age, 77 ± 14 y). Fifty-six (49.6%) achieved successful liberation, and 33 (29%) died in the ICU. The mean ± SD duration of mechanical ventilation was 14.4 ± 6.7 d. The Bland-Altman diagrams that addressed intra- and interobservers agreement showed low variability between measurements. Values of the concordance coefficients of kappa were 0.82 (0.68–0.95) and 0.80 (0.65–0.94), and of the linear correlation coefficients, 0.86 (0.77–0.91) and 0.89 (0.82–0.93) for the intra- and interobservers measurements, respectively. The mean ± SD values for the area under the curve for each pair of the intra- and interobserver measurements were 0.96 ± 0.07 versus 0.94 ± 0.07 (P = .41) and 0.94 ± 0.05 versus 0.90 ± 0.07 (P = .14), respectively.CONCLUSIONS:The variability of the measurement of the timed inspiratory effort index by intra- and interobservers showed very high reproducibility, which reinforced the index as a sensible, accurate, and reliable outcome predictor of liberation from mechanical ventilation.




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Ocrelizumab initiation in patients with MS: A multicenter observational study

Objective

To provide first real-world experience on patients with MS treated with the B cell–depleting antibody ocrelizumab.

Methods

We retrospectively collected data of patients who had received at least 1 treatment cycle (2 infusions) of ocrelizumab at 3 large neurology centers. Patients' characteristics including premedication, clinical disease course, and documented side effects were analyzed.

Results

We could identify 210 patients (125 women, mean age ± SD, 42.1 ± 11.4 years) who had received ocrelizumab with a mean disease duration of 7.3 years and a median Expanded Disability Status Scale score of 3.75 (interquartile range 2.5–5.5; range 0–8). Twenty-six percent of these patients had a primary progressive MS (PPMS), whereas 74% had a relapsing-remitting (RRMS) or active secondary progressive (aSPMS) disease course. Twenty-four percent of all patients were treatment naive, whereas 76% had received immune therapies before. After ocrelizumab initiation (median follow-up was 200 days, range 30–1,674 days), 13% of patients with RRMS/aSPMS experienced a relapse (accounting for an annualized relapse rate of 0.17, 95% CI 0.10–0.24), and 5% of all patients with MS experienced a 12-week confirmed disability progression. Treatment was generally well tolerated, albeit only short-term side effects were recorded, including direct infusion-related reactions and mild infections.

Conclusions

We provide class IV evidence that treatment with ocrelizumab can stabilize naive and pretreated patients, indicating that ocrelizumab is an option following potent MS drugs such as natalizumab and fingolimod. Further studies are warranted to confirm these findings and to reveal safety concerns in the longer-term follow-up.

Classification of evidence

This study provides Class IV evidence that for patients with MS, ocrelizumab can stabilize both treatment-naive and previously treated patients.




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Direct Determination of Pyrazinamide (PZA) Susceptibility by Sputum Microscopic Observation Drug Susceptibility (MODS) Culture at Neutral pH: the MODS-PZA Assay [Mycobacteriology and Aerobic Actinomycetes]

Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of Mycobacterium tuberculosis. However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH. Here, for the first time, MODS culture at neutral pH was evaluated using high PZA concentrations (400 and 800 μg/ml) to determine PZA susceptibility directly from sputum samples. Sputum samples were cultured with PZA for up to 21 days at 37°C. Plate reading was performed at two time points: R1 (mean, 10 days) and R2 (mean, 13 days) for each PZA concentration. A consensus reference test, composed of MGIT-PZA, pncA sequencing, and the classic Wayne test, was used. A total of 182 samples were evaluated. The sensitivity and specificity for 400 μg/ml ranged from 76.9 to 89.7 and from 93.0 to 97.9%, respectively, and for 800 μg/ml ranged from 71.8 to 82.1 and from 95.8 to 98.6%, respectively. Compared to MGIT-PZA, our test showed a similar turnaround time (medians of 10 and 12 days for PZA-sensitive and -resistant isolates, respectively). In conclusion, MODS-PZA is presented as a fast, simple, and low-cost DST that could complement the MODS assay to evaluate resistance to the principal first-line antituberculosis drugs. Further optimization of test conditions would be useful in order to increase its performance.




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Checking responses of goal- and sign-trackers are differentially affected by threat in a rodent analog of obsessive-compulsive disorder [RESEARCH]

In obsessive–compulsive disorder (OCD), functional behaviors such as checking that a door is locked become dysfunctional, maladaptive, and debilitating. However, it is currently unknown how aversive and appetitive motivations interact to produce functional and dysfunctional behavior in OCD. Here we show a double dissociation in the effects of anxiogenic cues and sensitivity to rewarding stimuli on the propensity to develop functional and dysfunctional checking behavior in a rodent analog of OCD, the observing response task (ORT). While anxiogenic manipulations of perceived threat (presentation of threat-associated contextual cues) and actual threat (punishment of incorrect responding on the ORT) enhanced functional checking, dysfunctional checking was unaffected. In contrast, rats that had previously been identified as "sign-trackers" on an autoshaping task—and therefore were highly sensitive to the incentive salience of appetitive environmental cues—selectively showed elevated levels of dysfunctional checking under a range of conditions, but particularly so under conditions of uncertainty. These data indicate that functional and dysfunctional checking are dissociable and supported by aversive and appetitive motivational processes, respectively. While functional checking is modulated by perceived and actual threat, dysfunctional checking recruits appetitive motivational processes, possibly akin to the "incentive habits" that contribute to drug-seeking in addiction.




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National Surgical, Obstetric, and Anesthesia Plans Supporting the Vision of Universal Health Coverage




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Severe treatment-refractory T-cell-mediated immune skin toxicities observed with obinutuzumab/rituximab-atezo-pola in two patients with follicular lymphoma




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Brief interventions for obesity when patients are asked to pay for weight loss treatment: an observational study in primary care with an embedded randomised trial

BackgroundA brief intervention whereby GPs opportunistically facilitate an NHS-funded referral to a weight loss programme is clinically and cost-effective.AimTo test the acceptability of a brief intervention and attendance at a weight loss programme when GPs facilitate a referral that requires patients to pay for the service.Design and settingAn observational study of the effect of a GP encouraging attendance at a weight loss programme requiring self-payment in the West Midlands from 16 October 2018 to 30 November 2018, to compare with a previous trial in England in which the service was NHS-funded.MethodSixty patients with obesity who consecutively attended primary care appointments received an opportunistic brief intervention by a GP to endorse and offer a referral to a weight loss programme at the patient’s own expense. Participants were randomised to GPs who either stated the weekly monetary cost of the programme (basic cost) or who compared the weekly cost to an everyday discretionary item (cost comparison). Participants were subsequently asked to report whether they had attended a weight loss programme.ResultsOverall, 47% of participants (n = 28) accepted the referral; 50% (n = 15) in the basic cost group and 43% (n = 13) in the cost comparison group. This was significantly less than in a previous study when the programme was NHS-funded (77%, n = 722/940; P<0.0001). Most participants reported the intervention to be helpful/very helpful and appropriate/very appropriate (78%, n = 46/59 and 85%, n = 50/59, respectively) but scores were significantly lower than when the programme was NHS-funded (92% n = 851/922 and 88% n = 813/922, respectively; P = 0.004). One person (2%) attended the weight loss programme, which is significantly lower than the 40% of participants who attended when the programme was NHS-funded (P<0.0001).ConclusionGP referral to a weight loss programme that requires patients to pay rather than offering an NHS-funded programme is acceptable; however, it results in almost no attendance.




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Proportion of female recipients of resident-selected awards across Canada from 2000 to 2018: a retrospective observational study

Background:

Female physicians have been shown to receive fewer awards from medical societies than their male colleagues. We examined the sex distribution of recipients of Canadian residency association awards.

Methods:

We conducted a retrospective observational study of the sex of staff and resident physician recipients of resident-selected awards from provincial and national residency associations using data from 2000–2018. We classified awards into professionalism, advocacy and wellness awards, and education and teaching awards based on award names and descriptions, and compared the proportion of male and female recipients in these categories.

Results:

We identified 314 recipients of staff physician awards and 129 recipients of resident physician awards. Male staff and resident physicians had higher odds of receiving awards than their female counterparts (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.13–1.89 and OR 1.70, 95% CI 1.18–2.46, respectively). There was a reduction in the odds of male residents’ receiving an award over the study period (OR 0.94, 95% CI 0.90–0.98). Male physicians had higher odds of receiving education and teaching awards than female physicians as staff but not as residents (OR 3.21, 95% CI 1.72–5.95 and OR 1.96, 95% CI 0.84–4.60, respectively).

Interpretation:

Male staff and resident physicians in Canada had higher odds of receiving awards from provincial and national residency associations between 2000 and 2018 than their female counterparts. Given this disparity, it would be prudent for organizations that distribute awards to physicians, residents and medical students to examine their nomination criteria and processes for potential bias.




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Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects

Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development.




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Screening for obstructive sleep apnoea in professional drivers

Professional drivers show a higher prevalence of obstructive sleep apnoea (OSA) compared with the general population. Furthermore, there is concern about the association between OSA and car crash risk given that drivers with OSA show an increased risk for car accidents. Despite this risk, OSA is often underdiagnosed and undertreated in this population, mainly due to lack of appropriate screening and sleep study referrals. Polysomnography (PSG), the gold standard test, is inappropriate for systematic screening because of its high expense, complexity and relative inaccessibility in this population. Therefore, there is a strong demand for good screening tools, including both subjective and objective data that may assist in early identification of possible OSA among professional drivers and, thus, aid in PSG examination referral and OSA management in an accredited sleep centre. However, there is considerable disagreement over screening methods and criteria for triggering a sleep study referral in different countries. There is also a strong need for further research in the area of OSA screening of commercial drivers in order to improve the diagnostic accuracy of screening tools and ensure that patients with OSA are accurately identified.

Key points

  • Obstructive sleep apnoea (OSA) is often undiagnosed and undertreated in professional drivers.

  • Professional drivers often under-report and are reluctant to report OSA symptoms.

  • Barriers to OSA diagnosis include appropriate screening and sleep study referrals.

  • Screening tools including both subjective and objective data may assist in early identification of possible OSA among professional drivers.

  • Educational aims

  • To evaluate screening instruments currently used to identify OSA risk in professional drivers.

  • To provide guidance for developing an assessment strategy for OSA by professional driver medical examiners.




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    A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study [Antiviral Agents]

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.)




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    Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study [INTERVENTIONAL]

    BACKGROUND AND PURPOSE:

    Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.

    MATERIALS AND METHODS:

    In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study.

    RESULTS:

    In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best ( ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial ( > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters’ judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial ( ≤ 0.6).

    CONCLUSIONS:

    The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.




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    Robots are taking manufacturing jobs but making firms more productive

    Robots are replacing manufacturing workers in France, making companies more productive and reducing employment across the industry




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    AI and the Future of Work: The Prospects for Tomorrow’s Jobs

    MIT conference considers companies that have implemented job-friendly AI



    • robotics
    • robotics/artificial-intelligence

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    Police stop fewer black drivers at night when a 'veil of darkness' obscures their race

    After analyzing 95 million traffic stop records, filed by officers with 21 state patrol agencies and 35 municipal police forces from 2011 to 2018, researchers concluded that 'police stops and search decisions suffer from persistent racial bias.'




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    Jobs Report Reveals Racial Inequality in Unemployment at an Historic Low, Thanks to Pandemic

    More than 20 million Americans lost their jobs in the last month, and unemployment among African-Americans has hit 16.7 percent.




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    NASA’s Neil Gehrels Swift Observatory Tracks Water Loss from Interstellar Comet 2I/Borisov

    Astronomers using NASA’s Neil Gehrels Swift Observatory have tracked water loss from 2I/Borisov, the first known interstellar comet to visit our Solar System, as it approached and rounded the Sun. Their findings were published in the Astrophysical Journal Letters. 2I/Borisov was detected on August 30, 2019 by Gennady Borisov, an astronomer at the Crimean Astrophysical [...]




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    Juno, Hubble, Gemini Observatory Probe Jovian Storm Systems

    Multiwavelength observations from the NASA/ESA Hubble Space Telescope and Gemini Observatory combined with close-up views from NASA’s Juno spacecraft reveal that lightning strikes and huge storm systems that create them in Jupiter’s atmosphere are formed in and around large convective cells over deep clouds of water ice and liquid; the observations also confirm that dark [...]




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    Jessica Simpson feels 'body shamed' for 'having boobs'

    The 39-year-old star has fired back at Vogue editor Sally Singer after a piece reflecting on the 2007 Met Gala which criticised her low cut




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    10 takeaways from the worst jobs report in US history

    BALTIMORE (AP) - Brutal. Horrific. Tragic.

    Choose your description. The April jobs report showed, in harrowing detail, just how terribly the coronavirus outbreak has pummeled the U.S. economy. Most obviously, there's the 14.7% unemployment rate, the highest since the Great Depression. And the shedding of more than 20 million jobs, ...




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    Statistics Canada says it is probing leak of April jobs data half an hour before official release

    Data leaks of this magnitude are virtually unheard of in Canada




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    ‘Horrifically swift’: Canada lost almost two million jobs in April; jobless rate soars to 13%

    Roughly three million jobs have been lost over the past two months, the steepest consecutive monthly declines in employment ever recorded




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    Congress moves to give away national lands, discounting billions in revenue and millions of jobs

    Though recreation on public lands creates $646bn in economic stimulus and 6.1m jobs, Republicans are setting in motion a giveaway of Americans’ birthright

    In the midst of highly publicized steps to dismantle insurance coverage for 32 million people and defund women’s healthcare facilities, Republican lawmakers have quietly laid the foundation to give away Americans’ birthright: 640m acres of national land. In a single line of changes to the rules for the House of Representatives, Republicans have overwritten the value of federal lands, easing the path to disposing of federal property even if doing so loses money for the government and provides no demonstrable compensation to American citizens.

    At stake are areas managed by the Bureau of Land Management (BLM), National Forests and Federal Wildlife Refuges, which contribute to an estimated $646bn each year in economic stimulus from recreation on public lands and 6.1m jobs. Transferring these lands to the states, critics fear, could decimate those numbers by eliminating mixed-use requirements, limiting public access and turning over large portions for energy or property development.

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