Spring migration patterns of red knots in the Southeast United States disentangled using automated telemetry.

Red Knots use the Southeast United States as a stopover during north and southbound migration and during the winter. We examined northbound red knot migration routes and timing using an automated telemetry network. Our primary goal was to evaluate the relative use of an Atlantic migratory route through Delaware Bay versus an inland route through the Great Lakes en route to Arctic breeding grounds and to identify areas of apparent stopovers. Secondarily, we explored the association of red knot routes and ground speeds with prevailing atmospheric conditions. Most Red Knots migrating north from the Southeast United States skipped or likely skipped Delaware Bay (73%) while 27% of the knots stopped in Delaware Bay for at least 1 day. A few knots used an Atlantic Coast strategy that did not include Delaware Bay, relying instead on the areas around Chesapeake Bay or New York Bay for stopovers. Nearly 80% of migratory trajectories were associated with tailwinds at departure. Most knots tracked in our study traveled north through the eastern Great Lake Basin, without stopping, thus making the Southeast United States the last terminal stopover for some knots before reaching boreal or Arctic stopover sites.

Estimating detection for salt-marsh songbirds during winter using the double-pass rope-drag technique.

Bird species that are restricted to tidal marshes during one or all of their life stages are under increasing pressure from sea-level rise. To date, most of the research focused on this group has been conducted during the breeding season despite the fact that more than half of the annual cycle is spent on wintering grounds and the high likelihood that the winter period is the most critical time for adult survival. We used a double-pass rope-drag technique to estimate the winter abundance of sharp-tailed sparrows (Ammospiza nelson and A. caudacutus collectively), seaside sparrows (A. maritimus) and marsh wrens (Cistothorus palustris) within tidal marshes of Virginia along 102 60X250 m transects between January and March, 2014. We used the first pass to remove birds from the transect and the second pass was used to estimate detection probabilities. The technique was highly effective producing detection rates of 98% for sharp-tailed sparrows, 95% for seaside sparrows, and 91% for marsh wrens. We conducted three rounds of surveys and found that species-specific detection rates were comparable when we restricted our analyses to two survey rounds. Availability and abundance estimates deviated to a greater degree than detection rates when restricting data to that collected during only two rounds but confidence intervals overlapped for all three taxa, regardless of which two survey periods were used for the comparison. However, results were less precise when we restricted our analyses to two of three rounds with confidence intervals averaging 13%, 45%, and 14% larger for detection, availability, and abundance respectively. The double-pass rope-drag technique provides an effective, unbiased sampling technique to estimate winter songbird abundance in saltmarsh habitat provided that at least two rounds are used and increasing the number of survey rounds will result in more precise estimates.

Using the natural abundance of nitrogen isotopes to identify cattle with greater efficiency in protein-limiting diets.

The difficulty in selecting cattle for higher feed and nitrogen use efficiency (NUE) is an important factor contributing to poor growth and reproductive performance in dry-tropics rangelands. Therefore, the objectives were to examine the cattle variation in retaining nitrogen in a protein-deficient diet and the natural abundance of stable isotopes in body tissues as a practical alternative for the detection of more efficient cattle. In experiment 1, feed efficiency parameters were determined in 89 Brahman steers fed a protein-limiting diet for 70 days, followed by 7 days in metabolism crates for total collection of urine and faeces and calculation of nitrogen retention and NUE. The diet-animal fractionation of nitrogen isotopes (Δ15N) was quantified in tail hair and plasma proteins using isotope-ratio MS. There was a large variation in growth performance, feed efficiency and nitrogen losses among steers. Quantifying Δ15N in tail hair (Δ15Ntail hair) resulted in stronger correlations with feed efficiency and nitrogen metabolism parameters than when quantified in plasma proteins. Δ15Ntail hair was positively correlated with nitrogen losses in urine (r = 0.31, P < 0.01) and faeces (r = 0.25, P = 0.04), leading to a negative correlation with NUE (r = -0.40, P < 0.01). The group of steers with lower Δ15Ntail hair had greater feed efficiency, lower nitrogen losses, and greater NUE. In experiment 2, for evaluation of isotope fraction as a predictor of reproductive performance, 630 Brahman-crossed cows were classified for reproductive performance for 2 years. From this group, 25 cows with poor reproductive performance and 25 cows with good reproductive performance were selected. Tail hair representing 7 months of growth were segmented and analysed for carbon (δ13C) and nitrogen (δ15N) isotope enrichment. Reproductive performance was not associated with diet selection, as there was no difference in tail hair δ13C between groups. However, more productive cows had lower (P < 0.05) tail hair δ15N during the dry season, indicating differences in N metabolism and possibly lower N losses. In addition, cows with better reproductive performance and, therefore, greater nutrient demands, had similar body condition scores and a tendency (P = 0.09) for higher live weight at the end of the trial. In conclusion, the findings of the present study confirm that nitrogen isotope fractionation in tail hair can be used as a predictor of nitrogen losses, NUE, and reproductive performance of Brahman cattle on low-protein diets.

Drug resistance in leprosy: An update following 70years of chemotherapy.

Leprosy is one of the oldest infectious diseases, reported for more than 2000years. Leprosy elimination goal as a public health problem set by the World Health Organization, aiming for a global prevalence rate<1 patient in a population of 10,000, was achieved in 2000 mainly thanks to the worldwide use of leprosy drugs starting in the 1980s and their access at no cost for patients since 1995. However, around 200,000 new cases are still reported each year, particularly in India, Brazil, and Indonesia. As with other bacteria of medical interest, antimicrobial resistance is observed in Mycobacterium leprae strains in several parts of the world, despite multidrug therapy being the recommended standard leprosy treatment to avoid resistance selection since 1982. Therefore, identifying and monitoring resistance is necessary. We provide an overview of the historical facts that led to the current drug resistance situation, the antibiotics effective against M. leprae, their mechanisms of action and resistance, and resistance detection methods. We also discuss therapeutic management of the resistant cases, new genes with potential roles in drug resistance and bacterial adaptation, new drugs under investigation, and the risk for resistance selection with the chemoprophylaxis measures.

Drug resistance in leprosy: an update following 70 years of chemotherapy

Leprosy is one of the oldest infectious diseases, reported for more than 2000 years. Leprosy elimination goal as a public health problem set by the World Health Organization, aiming for a global prevalence rate < 1 patient in a population of 10,000, was achieved in 2000 mainly thanks to the worldwide use of leprosy drugs starting in the 1980s and their access at no cost for patients since 1995. However, around 200,000 new cases are still reported each year, particularly in India, Brazil, and Indonesia. As with other bacteria of medical interest, antimicrobial resistance is observed in Mycobacterium leprae strains in several parts of the world, despite multidrug therapy being the recommended standard leprosy treatment to avoid resistance selection since 1982. Therefore, identifying and monitoring resistance is necessary. We provide an overview of the historical facts that led to the current drug resistance situation, the antibiotics effective against M. leprae, their mechanisms of action and resistance, and resistance detection methods. We also discuss therapeutic management of the resistant cases, new genes with potential roles in drug resistance and bacterial adaptation, new drugs under investigation, and the risk for resistance selection with the chemoprophylaxis measures.

The annual cycle for whimbrel populations using the Western Atlantic Flyway.

Many long-distance migratory birds use habitats that are scattered across continents and confront hazards throughout the annual cycle that may be population-limiting. Identifying where and when populations spend their time is fundamental to effective management. We tracked 34 adult whimbrels (Numenius phaeopus) from two breeding populations (Mackenzie Delta and Hudson Bay) with satellite transmitters to document the structure of their annual cycles. The two populations differed in their use of migratory pathways and their seasonal schedules. Mackenzie Delta whimbrels made long (22,800 km) loop migrations with different autumn and spring routes. Hudson Bay whimbrels made shorter (17,500 km) and more direct migrations along the same route during autumn and spring. The two populations overlap on the winter grounds and within one spring staging area. Mackenzie Delta whimbrels left the breeding ground, arrived on winter grounds, left winter grounds and arrived on spring staging areas earlier compared to whimbrels from Hudson Bay. For both populations, migration speed was significantly higher during spring compared to autumn migration. Faster migration was achieved by having fewer and shorter stopovers en route. We identified five migratory staging areas including four that were used during autumn and two that were used during spring. Whimbrels tracked for multiple years had high (98%) fidelity to staging areas. We documented dozens of locations where birds stopped for short periods along nearly all migration routes. The consistent use of very few staging areas suggests that these areas are integral to the annual cycle of both populations and have high conservation value.

Whimbrel populations differ in trans-atlantic pathways and cyclone encounters.

Each year hundreds of millions of birds cross the Atlantic Ocean during the peak of tropical cyclone activity. The extent and consequences of migrant-storm interactions remain unknown. We tracked whimbrels from two populations (Mackenzie Delta; Hudson Bay) to examine overlap between migration routes and storm activity and both the frequency and consequence of storm encounters. Here we show that Mackenzie Delta and Hudson Bay whimbrels follow different routes across the ocean and experience dramatically different rates of storm encounters. Mackenzie Delta whimbrels departed North America from Atlantic Canada, made long ([Formula: see text] = 5440 ± 120.3 km) nonstop flights far out to sea that took several days ([Formula: see text] = 6.1 ± 0.18) to complete and encountered storms during 3 of 22 crossings. Hudson Bay whimbrels departed North America from the south Atlantic Coast, made shorter ([Formula: see text] = 3643 ± 196.2 km) nonstop flights across the Caribbean Basin that took less time ([Formula: see text] = 4.5 ± 0.29) to complete and encountered storms during 13 of 18 crossings. More than half of Hudson Bay storm encounters resulted in groundings on Caribbean islands. Grounded birds required longer ([Formula: see text] = 30.4 ± 5.32 days) to complete trans-Atlantic crossings and three were lost including 2 to hunters and 1 to a predator. One of the Mackenzie Delta whimbrels was lost at sea while crossing the Intertropical Convergence Zone. Whimbrels use two contrasting strategies to cross the Atlantic including (1) a long nonstop flight around the core of storm activity with a low likelihood of encountering storms but no safety net and (2) a shorter flight through the heart of Hurricane Alley with a high likelihood of encountering storms and a safety network of islands to use in the event of an encounter. Demographic consequences of storm encounters will likely play a role in the ongoing evolution of trans-Atlantic migration pathways as global temperatures continue to rise.

Identification of Streptococcus pneumoniae in hospital-acquired pneumonia in adults.

Hospital-acquired pneumonia (HAP) is often more severe and life-threatening than community-acquired pneumonia (CAP). The role of Streptococcus pneumoniae in CAP is well-understood, but its role in HAP is unclear. The objective of this study was to summarize the available literature on the prevalence of S. pneumoniae in HAP episodes. We searched MEDLINE for peer-reviewed articles on the microbiology of HAP in individuals aged ≥18 years, published between 2008 and 2018. We calculated pooled estimates of the prevalence of S. pneumoniae in episodes of HAP using a random-effects, inverse-variance-weighted meta-analysis. Forty-seven of 1908 articles met the inclusion criteria. Bacterial specimen isolation techniques for microbiologically defined HAP episodes included bronchoalveolar lavage, protective specimen brush, tracheobronchial aspirate and sputum, as well as blood culture. Culture was performed in all studies; five studies also used urine antigen detection (5/47; 10.6%). S. pneumoniae was identified in 5.1% (95% confidence interval (CI): 3.8-6.6%) of microbiologically defined HAP episodes (N = 20), with 5.4% (95% CI: 4.3-6.7%, N = 29) in ventilator-associated HAP and 6.0% (95% CI: 4.1-8.8%, N = 6) in non-ventilator-associated HAP. S. pneumoniae was identified in 5.3% (95% CI: 4.5-6.3%) of HAP occurring in the intensive care unit (ICU, N = 41) and in 5.6% (95% CI: 3.3-9.5%, N = 5) outside the ICU. A higher proportion of early-onset HAP (10.3%; 95% CI: 8.3-12.8%, N = 16) identified S. pneumoniae as compared with late-onset HAP (3.3%; 95% CI: 2.5-4.4%, N = 16). In conclusion, S. pneumoniae was identified by culture in 5.1% of microbiologically defined HAP episodes. The importance of HAP as part of the disease burden caused by S. pneumoniae merits further research.

The impacts of intensive mining on terrestrial and aquatic ecosystems: A case of sediment pollution and calcium decline in cool temperate Tasmania, Australia.

Mining causes extensive damage to aquatic ecosystems via acidification, heavy metal pollution, sediment loading, and Ca decline. Yet little is known about the effects of mining on freshwater systems in the Southern Hemisphere. A case in point is the region of western Tasmania, Australia, an area extensively mined in the 19th century, resulting in severe environmental contamination. In order to assess the impacts of mining on aquatic ecosystems in this region, we present a multiproxy investigation of the lacustrine sediments from Owen Tarn, Tasmania. This study includes a combination of radiometric dating (14C and 210Pb), sediment geochemistry (XRF and ICP-MS), pollen, charcoal and diatoms. Generalised additive mixed models were used to test if changes in the aquatic ecosystem can be explained by other covariates. Results from this record found four key impact phases: (1) Pre-mining, (2) Early mining, (3) Intense mining, and (4) Post-mining. Before mining, low heavy metal concentrations, slow sedimentation, low fire activity, and high biomass indicate pre-impact conditions. The aquatic environment at this time was oligotrophic and dystrophic with sufficient light availability, typical of western Tasmanian lakes during the Holocene. Prosperous mining resulted in increased burning, a decrease in landscape biomass and an increase in sedimentation resulting in decreased light availability of the aquatic environment. Extensive mining at Mount Lyell in the 1930s resulted in peak heavy metal pollutants (Pb, Cu and Co) and a further increase in inorganic inputs resulted in a disturbed low light lake environment (dominated by Hantzschia amphioxys and Pinnularia divergentissima). Following the closure of the Mount Lyell Co. in 1994 CE, Ca declined to below pre-mining levels resulting in a new diatom assemblage and deformed diatom valves. Therefore, the Owen Tarn record demonstrates severe sediment pollution and continued impacts of mining long after mining has stopped at Mt. Lyell Mining Co.

Characterization and clinical course of 1000 patients with COVID-19 in New York: retrospective case series.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. DESIGN: Retrospective manual medical record review. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. PARTICIPANTS: The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. MAIN OUTCOME MEASURES: Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. RESULTS: Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. CONCLUSIONS: Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series

ObjectiveTo characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). DesignRetrospective manual medical record review. SettingNewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. ParticipantsThe first 1000 consecutive patients with laboratory-confirmed COVID-19. MethodsWe identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measuresWe describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. ResultsAmong the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. ConclusionsHospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Blubber cortisol levels in humpback whales (Megaptera novaeangliae): A measure of physiological stress without effects from sampling.

Baleen whales are vulnerable to environmental impacts due to low fecundity, capital breeding strategies, and their reliance on a large amount of prey resources over large spatial scales. There has been growing interest in monitoring health and physiological stress in these species but, to date, few measures have been validated. The purpose of this study was to examine whether blubber cortisol could be used as a measure of physiological stress in humpback whales. Cortisol concentrations were initially compared between live, presumably 'healthy' whales (n = 187) and deceased whales (n = 35), which had died after stranding or entanglement, or washed ashore as a carcass. Deceased whales were found to have significantly higher cortisol levels (mean ± SD; 5.47 ± 4.52 ng/g) than live whales (0.51 ± 0.14 ng/g; p < 0.001), particularly for those animals that had experienced prolonged trauma (e.g. stranding) prior to death. Blubber cortisol levels in live whales were then examined for evidence of life history-related, seasonal, or sampling-related effects. Life history group and sampling-related factors, such as encounter time and the number of biopsy sampling attempts per animal, were found to be poor predictors of blubber cortisol levels in live whales. In contrast, blubber cortisol levels varied seasonally, with whales migrating north towards the breeding grounds in winter having significantly higher levels (0.54 ± 0.21 ng/g, p = 0.016) than those migrating south towards the feeding grounds in spring (0.48 ± 1.23 ng/g). These differences could be due to additional socio-physiological stress experienced by whales during peaks in breeding activity. Overall, blubber cortisol appears to be a suitable measure of chronic physiological stress in humpback whales.

Liquid chromatography tandem mass spectrometry for the quantification of steroid hormone profiles in blubber from stranded humpback whales (Megaptera novaeangliae).

Marine mammal blubber is known to have quantifiable concentrations of steroid hormones and is increasingly chosen as a matrix for the detection of these reproductive and stress biomarkers. Steroid hormones act through complex cascades, often in concert, yet studies conducted on cetaceans have rarely measured more than two steroids simultaneously. Due to the role of steroid hormones in multiple physiological processes, and variability in concentration among individuals, data on single compounds are often difficult to interpret. Here a liquid chromatography tandem mass spectrometry method for the simultaneous analyses of multiple steroid hormones in cetacean blubber was validated and applied to samples from 10 stranded humpback whales (Megaptera novaeangliae). Progesterone, 17α-hydroxyprogesterone, testosterone, androstenedione, oestrone, oestradiol, cortisone, cortisol, corticosterone and 11-deoxycorticosterone were reliably (relative standard deviation on six replicates <15%) and accurately (recovery of an amended sample between 70% and 120%) quantified, but not 11-deoxycortisol. With the exception of progesterone, testosterone, oestradiol and cortisol, these compounds were quantified for the first time in humpback whales. Given that blubber is frequently collected from free-swimming cetaceans in ongoing research programs, the technique developed here could substantially strengthen understanding and monitoring of the physiological condition of these species.

Psychological distress among primary school teachers: a comparison with clinical and population samples.

OBJECTIVES: This analysis explored the level of psychological distress among primary school teachers in the South West of England as compared with clinical and general population samples. STUDY DESIGN: Secondary analysis of data from the Supporting Teachers and Children in Schools (STARS) trial completed by up to 90 teachers at baseline, 9, 18 and 30 months of follow-up. METHODS: We used the Everyday Feelings Questionnaire (EFQ) as a measure of psychological distress. Baseline data on teachers were compared with a population sample of professionals and a clinical sample of patients attending a depression clinic. RESULTS: Our teacher cohort experienced higher levels of psychological distress than comparable professionals from the general population, which were sustained over 30 months of follow-up. Levels of psychological distress were lower than those found in the clinical sample. Using a cut-point indicative of moderate depression, our data suggest that between 19% and 29% of teachers experienced clinically significant distress at each time-point. CONCLUSIONS: We detected high and sustained levels of psychological distress among primary school teachers, which suggests an urgent need for intervention. Effective support for teachers' mental health is particularly important given the potential impact of poor teacher mental health on pupil well-being, pupil attainment and teacher-pupil relationships.

Silicon-Based Optical Mirror Coatings for Ultrahigh Precision Metrology and Sensing.

Thermal noise of highly reflective mirror coatings is a major limit to the sensitivity of many precision laser experiments with strict requirements such as low optical absorption. Here, we investigate amorphous silicon and silicon nitride as an alternative to the currently used combination of coating materials, silica, and tantala. We demonstrate an improvement by a factor of ≈55 with respect to the lowest so far reported optical absorption of amorphous silicon at near-infrared wavelengths. This reduction was achieved via a combination of heat treatment, final operation at low temperature, and a wavelength of 2 µm instead of the more commonly used 1550 nm. Our silicon-based coating offers a factor of 12 thermal noise reduction compared to the performance possible with silica and tantala at 20 K. In gravitational-wave detectors, a noise reduction by a factor of 12 corresponds to an increase in the average detection rate by three orders of magnitude (≈12^{3}).

Identifying Exosome-Derived MicroRNAs as Candidate Biomarkers of Frailty.

Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.

Paroxysmal nocturnal haemoglobinuria testing in blood transfusion laboratories: do they go with the flow?

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare stem cell disorder causing, in untreated patients, symptoms that include renal damage, thrombosis and increased mortality. When correctly diagnosed and treated, patients have reduced symptoms and normal life expectancies. Historically PNH testing resided within blood transfusion laboratories using techniques that were insensitive, for example, the Ham test. However, technology has evolved and flow cytometry is now regarded as the gold standard methodology. Given the clinical importance of diagnosing PNH correctly, we undertook a study to examine PNH testing procedures in blood transfusion laboratories within the UK and Ireland to determine implementation of best practices. An online survey was issued to 386 blood transfusion laboratories in the UK and Ireland requesting details of their current PNH testing practices and procedures. There were 143 responses, representing a 37% response rate. Of these, we identified seven laboratories undertaking PNH testing using obsolete methodologies. Furthermore, multiple centres did not refer samples for confirmatory testing by national PNH reference centres and inclusion on the national PNH disease registry. Staff handling requests for PNH testing should ensure that all samples are tested in accordance with current best practices using only flow cytometry.

A novel application of the Staudinger ligation to access neutral cyclic di-nucleotide analog precursors via a divergent method.

Our efforts to develop a scalable and divergent synthesis of cyclic di-nucleotide analog precursors have resulted in (1) an orthogonally protected di-amino carbohydrate as well as (2) the novel application of the Staudinger ligation to provide medium-sized macrocycles featuring carbamate or urea linkages.

A survey of patients with surgical wounds healing by secondary intention; an assessment of prevalence, aetiology, duration and management.

BACKGROUND: Surgical wounds healing by secondary intention (SWHSI) are often difficult and costly to treat. There is a dearth of clinical and research information regarding SWHSI. The aim of this survey was to estimate the prevalence of SWHSI and to characterise the aetiology, duration and management of these wounds. METHODS: Anonymised data were collected from patients with SWHSI receiving treatment in primary, secondary and community settings. Over a two weeks period, data were collected on the patients, their SWHSI, clinical and treatment details. RESULTS: Data were collected from 187 patients with a median age of 58.0 (95% CI = 55 to 61) years. The prevalence of SWHSI was 0.41 (95% CI = 0.35 to 0.47) per 1000 population. More patients with SWHSI were being treated in community (109/187, 58.3%) than in secondary (56/187, 29.9%) care settings. Most patients (164/187, 87.7%) had one SWHSI and the median duration of wounds was 28.0 (95% CI = 21 to 35) days. The most common surgical specialities associated with SWHSI were colorectal (80/187, 42.8%), plastics (24/187, 12.8%) and vascular (22/187, 11.8%) surgery. Nearly half of SWHSI were planned to heal by secondary intention (90/187, 48.1%) and 77/187 (41.2%) were wounds that had dehisced. Dressings were the most common single treatment for SWHSI, received by 169/181 (93.4%) patients. Eleven (6.1%) patients were receiving negative pressure wound therapy. CONCLUSIONS: This survey provides a previously unknown insight into the occurrence, duration, treatment and types of surgery that lead to SWHSI. This information will be of value to patients, health care providers and researchers.