A model including standardized weight improved predicting waiting list mortality in adolescent liver transplant candidates: A US national study.

The Model for End-Stage Liver Disease (MELD) score has been employed to identify adolescents eligible for liver transplantation since 2004. However, the optimal model for prioritizing adolescent candidates is uncertain. In our study, we aimed at evaluating the value of adding anthropometric variables to liver transplantation allocation models among adolescents. We conducted a retrospective cohort study using the data from the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research to identify adolescent patients registered on the liver transplant waiting list in the United States between January 1, 2003, and December 31, 2022. Adolescents (12-17 y) who were listed for their first liver transplantation were included. We evaluated the performance of different models including pediatric end-stage liver disease with Na and creatinine, MELD, and MELD 3.0. Furthermore, we evaluated whether adding anthropometric variables ( z -score for weight and height) would improve the models' performance for our primary outcome (mortality at 90 days after listing). We identified 1421 eligible adolescent patients. Adding a z -score of weight (MELD-TEEN) improved the performance and discrimination of the MELD score. The final model including weight z -score (MELD-TEEN) had better discriminative power compared to MELD 3.0 and pediatric end-stage liver disease with Na and creatinine in the overall cohort and in different age groups (ages 12-14 and 15-17). MELD-TEEN could improve the accuracy of allocation of liver transplants among adolescents by incorporating the weight z -score compared to MELD 3.0 and pediatric end-stage liver disease with Na and creatinine.

Management of patients with chronic kidney disease: a French medical centre database analysis.

OBJECTIVE(S): Chronic kidney disease (CKD) is an insidious disease that requires early nephroprotective measures to delay progression to end-stage kidney disease. The objective of this study was to describe the management of patients with CKD in primary care, including clinical and biological monitoring and prescribed treatments. A retrospective, single-centre study was conducted on adult patients who were treated in the Maison de Neufchâtel (France) between 2012 and 2017 at least once a year. The inclusion criteria were 2 estimated glomerular filtration rate (eGFR) measurements <60 mL/min more than 3 months apart. Two subgroups were constituted according to whether CKD was coded in the electronic medical records (EMRs). RESULTS: A total of 291 (6.7%, CI95% 5.9-7.4) patients with CKD were included. The mean eGFR was 51.0 ± 16.4 mL/min. Hypertension was the most frequent health problem reported (n = 93, 32%). Nephrotective agents were prescribed in 194 (66.7%) patients, non-steroidal anti-inflammatory drugs (NSAIDs) in 22 (8%) patients, and proton-pump inhibitors (PPIs) in 147 (47%) patients. CKD coding in EMRs was associated with dosage of natraemia (n = 34, 100%, P < 0.01), albuminuria (n = 20, 58%, P < 0.01), vitamin D (n = 14, 41%, P < 0.001), and phosphorus (n = 11, 32%, P < 0.001). Eighty-one patients (31.5%) with low eGFR without an entered code for CKD were prescribed an albuminuria dosage. Clinical monitoring could not be analysed due to poor coding. CONCLUSION: This pilot study reinforces the hypothesis that CKD is underscreened and undermanaged. More systematic coding of medical information in EMRs and further studies on medical centre databases should improve primary care practices.

Chronic kidney disease (CKD) is an insidious disease that requires early protective measures to delay progression to end-stage kidney disease. The aim of this study was to describe the management of patients with CKD in primary care. A study was conducted in France by analysing the medical records of adult patients between 2012 and 2017. Of 4,370 patients, 291 (6.7%) had CKD. Hypertension was the main associated medical history (32%) and was also known to be one of the main risk factors for CKD. Ninety-seven patients (33%) did not receive any medication indicated to protect the kidneys. Kidney-toxic drugs were widely prescribed, including PPIs in 47% of patients and NSAIDs in 8% of patients. Patients with a CKD note in their medical record had closer biological monitoring. This pilot study reinforces the hypothesis that CKD is underscreened and undermanaged. The coding of information in primary care and further studies on these databases should improve the practice of general practice.

Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.

BACKGROUND: The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others. METHODS: The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics. RESULTS: Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness. CONCLUSIONS: The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.

An assessment of the validity and reliability of the P022-P version of e-Celsius core temperature capsules.

Core temperature monitoring is a research tool used in many studies, though most popularly, heat strain. Ingestible core temperature capsules are a non-invasive and increasingly popular choice for measuring core body temperature, particularly considering the well-established validation of capsule systems. A newer version of the e-Celsius ingestible core temperature capsule has been released since the preceding validation study resulting in a paucity of validated research for the current version of capsules, P022-P, used by researchers. Using a 1:1 ratio of propylene glycol to water in a circulating water bath, and a reference thermometer with resolution and uncertainty of 0.01 °C, we assessed the validity and reliability of 24 P022-P e-Celsius capsules in three groups of eight, at seven temperature plateaus between 35 °C, and 42 °C in a test-retest format. The systematic bias of these capsules across all 3360 measurements was found to be -0.038 °C ± 0.086 °C (p < .001), The TEST-RETEST evaluation revealed excellent reliability by way of a minute overall mean difference of 0.0095 °C ± 0.048 °C (p < .001), and an intraclass correlation coefficient of 1.00 for each of TEST and RETEST conditions. Although quite small, differences in systematic bias across temperature plateaus were observed for both the OVERALL bias-between 0.00066 °C and 0.041°C-and TEST/RETEST bias-between 0.00010 °C and 0.016 °C. We found that the new capsule version outperforms manufacturer guarantees, with half of the systematic bias observed in a validation study of the previous capsule version. Though these capsules tend to slightly underestimate temperature, we find they possess excellent validity and reliability between 35 °C and 42 °C.

Goals of care documentation by medical oncologists and oncology patient end-of-life care outcomes.

BACKGROUND: Goals of care (GOC) documentation is important but underused. We aimed to improve oncologist GOC documentation and end-of-life (EOL) care. METHODS: In April 2020, our cancer center launched a GOC note template, including optional fields for documenting discussion with the patient about: cancer natural history, goals, and/or EOL (resuscitation preferences, hospice receptivity). Associations between GOC notes and EOL care were evaluated. RESULTS: Among 1721 patients dying between June 1, 2020 and June 30, 2021, median days from first GOC note (± with documentation of EOL discussion) to death was 92, whereas a GOC note including EOL discussion ("GOC EOL note"), specifically, was 31. Patients with a first GOC note >60 days before death spent fewer days inpatient (6.7 vs 10.6 days, p < .001). Among patients with GOC EOL notes, those with such documentation >30 days before death had fewer inpatient (5 vs 11, p < .001) and intensive care unit days (0.5 vs 1.5, p < .001), more hospice referrals (57% vs 44%, p = .003), and less chemotherapy ≤14 days before death (6% vs 11%, p = .010). Of 925 admissions of patients dying within ≤30 days, those with GOC EOL notes were shorter (7 vs 9 days, p = .013) but not associated with more hospice discharge (30% vs 25%, p = .163). Oncologist (vs nononcologist) GOC documentation and earlier documentation of EOL discussion were associated in subset analyses with less inpatient care and more hospice referrals. CONCLUSIONS: Documentation of GOC, including EOL discussions, is associated with favorable performance on accepted indicators of quality EOL care.

A UV-LED module that is highly effective at inactivating human coronaviruses and HIV-1.

Ultraviolet (UV) light has previously been established as useful method of disinfection, with demonstrated efficacy to inactivate a broad range of microorganisms. The advent of ultraviolet light-emitting diodes provides advantages in ease of disinfection, in that there can be delivery of germicidal UV with the same light unit that delivers standard white light to illuminate a room. Herein we demonstrate the efficacy and feasibility of ultraviolet light-emitting diodes as a means of decontamination by inactivating two distinct virus models, human coronavirus 229E and human immunodeficiency virus. Importantly, the same dose of ultraviolet light that inactivated human viruses also elicited complete inactivation of ultraviolet-resistant bacterial spores (Bacillus pumilus), a gold standard for demonstrating ultraviolet-mediated disinfection. This work demonstrates that seconds of ultraviolet light-emitting diodes (UV-LED) exposure can inactivate viruses and bacteria, highlighting that UV-LED could be a useful and practical tool for broad sanitization of public spaces.

Rethinking the need for a platelet transfusion threshold of 50 × 109 /L for lumbar puncture in cancer patients.

BACKGROUND: Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic procedure in oncology patients. Transfusing to a minimum preprocedural platelet threshold of 50 × 109 /L is widely upheld without good quality evidence. The objective was to compare the outcomes of LPs performed with platelets above and below this threshold. An increased risk of adverse events in patients with lower platelet counts was not expected. As a corollary, transfusion reaction rates incurred by transfusing to this recommended threshold are also reported. METHODS: A total of 2259 LPs performed on 1137 oncology patients (adult, n = 871, and pediatric, n = 266) were retrospectively analyzed between February 2011 and December 2017. The incidence of LP-related complications for groups above and below the minimum platelet threshold was compared. Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebral spinal fluid. Groups were compared using the 2-Proportion Z-test and Fisher exact test. RESULTS: At time of LP, the total number of events with platelets less than 50 × 109 /L and 50 × 109 /L or greater were 110 and 2149, respectively. There were no significant differences in LP-associated complications between patients with platelet counts above or below 50 × 109 /L (P = .29). Patients with a pre-LP platelet count of less than 50 × 109 /L had a higher proportion of traumatic taps (P < .001). Three patients developed transfusion-related adverse events. CONCLUSION: Patients with platelet counts less than 50 × 109 /L did not have a higher incidence of clinically significant post-lumbar puncture complications (P = .29).

Joint Spreading Factor and Channel Assignment in Multi-Operator LoRaWAN Deployments.

LoRaWAN is a popular internet of things (IoT) solution over the unlicensed radio band. It sustains low-cost, durable, and long range IoT wireless communications. Nonetheless, with over 24 billion connected IoT devices being expected by the end of the year, and over 50 billion by 2025, the concurrent and legacy approaches to spreading factor and channel assignment in LoRaWAN networks can no longer keep up. This is exacerbated with the growing densification of IoT device deployments and, with the increasing requirements for better throughput and packet delivery ratios. In this paper, we propose a proportional fair-based joint optimal formulation for spreading factor and channel assignment in multi-operator LoRaWAN deployments. The objective of this problem is to maximize the total sum of the logarithmic normalized throughput. We split the problem into two subproblems, and propose a game theoretic approach to solving them. We prove that our games converge towards a pure Nash equilibrium and, afterwards, solve the optimization problems using both semi-distributed and completely distributed algorithms. Via simulations, we show that our algorithms greatly improve the total normalized throughput for LoRaWAN as well as the packet success rate, in comparison to the legacy approaches.

Effects of an Acute Strength and Conditioning Training Session on Dual-Energy X-Ray Absorptiometry Results.

Lytle, JR, Stanelle, ST, Kravits, DM, Ellsworth, RL, Martin, SE, Green, JS, and Crouse, SF. Effects of an acute strength and conditioning training session on dual-energy x-ray absorptiometry results. J Strength Cond Res 34(4): 901-904, 2020-The purpose of this study was to determine whether an athletic strength and conditioning (S&C) session will alter body composition estimates of a dual-energy x-ray absorptiometry (DXA) scan. Twenty-two strength-trained individuals (15 men, 7 women, 24 ± 2 years, 174.2 ± 8.5 cm, 83.5 ± 15.0 kg) volunteered to participate in the study. Each subject underwent 2 DXA scans, before and after completion of the S&C session, which consisted of upper- and lower-body resistance exercises and interval running. Subjects consumed a free-living meal before the first scan, after which only ad libitum water intake was consumed until completing the second scan. Results were analyzed through sex by time repeated-measures analysis of variance. If no interaction effect was observed, results were next analyzed through correlated t-test (α = 0.05). Significant sex by time interactions were observed for arm total and lean mass, as well as a significant main effect of time showing a decrease in arm lean mass after the S&C session. Values before and after the S&C session that resulted in significant differences via correlated t-test are displayed in Table 1. Results revealed a significant decrease in total mass, arm and leg percent fat, and trunk lean mass, and an increase in leg lean mass.

Horizontal Transmission of Hepatitis B Virus From Mother to Child Due to Immune Escape Despite Immunoprophylaxis.

Hepatitis B virus (HBV) vaccination starting at birth is approximately 95% effective in preventing mother-to-child transmission to infants born to HBV-infected mothers. A higher risk of transmission is associated with birth to a highly viremic mother, often due to transplacental exposure, while later horizontal transmission is much less common, particularly following complete vaccination. This study reports a case of infection in an older child despite appropriate immunoprophylaxis starting at birth and an apparent protective immune response post-vaccination. Two immune escape mutations within the antigenic determinant of the surface antigen-coding region were observed in the child's dominant HBV sequence, whereas the maternal HBV variant lacked mutations at both sites. Ultra-deep sequencing confirmed the presence of 1 mutation at low levels within the maternal HBV quasispecies population, suggesting early exposure to the child followed by viral evolution resulting in immunoprophylaxis escape and chronic infection.

Understanding Geographic and Neighborhood Variations in Overdose Death Rates.

The current opioid epidemic continues to challenge us in new and potentially troubling ways. For example, research today finds more overdose deaths occurring in rural, rather than urban, geographic areas. Yet, studies have often ignored heterogeneities within these spaces and the neighborhood variations therein. Using geodemographic classification, we investigate neighborhood differences in overdose death rates by geographical areas to further understand where and among what groups the problem might be most concentrated. For deaths between 2013 and 2016, we find significant variation in rates among neighborhoods, defined by their socio-economic and demographic characteristics. For example, overdose death rates vary up to 13-fold among neighborhoods within geographic areas. Our results overall show that while the rural or urban classification of a geographic area is important in understanding the current overdose problem, a more segmented analysis by neighborhood's socio-economic and demographic makeup is also necessary.

Predicting V[Combining Dot Above]O2max From Treadmill Performance in American-Style Football Athletes.

Crouse, SF, Tolson, H, Lytle, J, Johnson, KA, Martin, SE, Green, JS, Oliver, J, Carbuhn, A, Lambert, B, and Bramhall, JP. Predicting V[Combining Dot Above]O2max from treadmill performance in American-style football athletes. J Strength Cond Res 33(4): 1028-1034, 2019-Prediction equations are often used to estimate V[Combining Dot Above]O2max in the general population but are lacking for American-style football (ASF) athletes. We sought to develop a regression model to estimate V[Combining Dot Above]O2max from treadmill exercise time in ASF athletes and compare our football V[Combining Dot Above]O2max model with 2 published prediction equations (Foster et al., 1984, and Bruce, 1973). American-style football athletes (N = 472, age = 18 ± 1 year, height = 186.1 ± 8.2 cm, and body mass = 101.8 ± 20.4 kg) underwent treadmill exercise to voluntary exhaustion (Bruce protocol). Maximal exercise time was recorded in minutes (Tmin), and V[Combining Dot Above]O2max was simultaneously measured (M-V[Combining Dot Above]O2max, mlO2·kg·min) by an automated gas-analysis system. Athletes were then randomly divided into validation and cross-validation groups (n = 236). Linear regression yielded estimates of V[Combining Dot Above]O2max from Tmin as follows: validation V[Combining Dot Above]O2max = 4.012 × Tmin - 4.628 (r = 0.678, p < 0.001, and SEE = 4.07); cross-validation V[Combining Dot Above]O2max = 4.025 × Tmin - 4.693 (r = 0.661, p < 0.001, and SEE = -4.16). These equations had a cross-validation coefficient of 0.813 and a double cross-validation coefficient of 0.823. Differences between the slopes of the 2 equations were not significant (t-test, p = 0.9603). Because validation and cross-validation groups were not statistically different on any variables measured (multivariate analysis of variance, p > 0.05), all athletes were combined to yield our final prediction equation: football V[Combining Dot Above]O2max = 4.017 × Tmin - 4.644 (r = 0.670, p < 0.001, and SEE = 4.11). Repeated-measures analysis of variance demonstrated significant differences (p < 0.001) in estimates of V[Combining Dot Above]O2max among Foster (44.1 ± 6.1), Bruce (47.1 ± 5.5), and our football (45.1 ± 5.8) equations. Foster and Bruce V[Combining Dot Above]O2max estimates were also significantly different from M-V[Combining Dot Above]O2max ((Equation is included in full-text article.)diff = -0.975 and 1.995, respectively, p < 0.001). V[Combining Dot Above]O2max of ASF athletes can be reasonably estimated by our football prediction equation using maximal treadmill time as the predictor.

Exposure-response characterization of tofacitinib efficacy in moderate to severe ulcerative colitis: Results from a dose-ranging phase 2 trial.

AIMS: Tofacitinib is an oral, small molecule JAK inhibitor being investigated for ulcerative colitis (UC). In a phase 2 dose-ranging study, tofacitinib demonstrated efficacy vs. placebo as UC induction therapy. In this posthoc analysis, we aimed to compare tofacitinib dose and plasma concentration as predictors of efficacy and identify covariates that determined efficacy in patients with UC. METHODS: One- and two-compartment pharmacokinetic models, with first-order absorption and elimination, were evaluated to describe plasma tofacitinib concentration-time data at baseline and week 8. Relationships between tofacitinib exposure (dose, average plasma drug concentration during a dosing interval at steady state [Cav,ss ] and trough plasma concentration at steady state [Ctrough,ss ]) and week 8 efficacy endpoints were characterized using logistic regression analysis. Baseline disease, demographics, prior and concurrent UC treatment were evaluated as covariates. RESULTS: Plasma tofacitinib concentrations increased proportionately with dose and estimated oral clearance, and Cav,ss values were not significantly different between baseline and week 8. Dose, Cav,ss and Ctrough,ss performed similarly as predictors of efficacy based on statistical criteria for model fit and comparison of model predictions for each endpoint. Individual Cav,ss values were similar between clinical remitters and nonremitters at predicted efficacious doses (10 and 15 mg twice daily). Baseline Mayo score was a significant determinant of efficacy. Predicted differences from placebo in clinical remission at 10 mg twice daily for patients with baseline Mayo score >8 and ≤8 were 39% (95% CI: 7-70) and 21% (-2-50), respectively. CONCLUSIONS: Exposure-response characterization demonstrated the potential of tofacitinib 10 and 15 mg twice daily as induction therapy for UC without monitoring of plasma drug concentrations for dose optimization.

Translation, psychometric validation, and baseline results of the Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures to assess health-related quality of life of patients with pediatric lymphoma in Malawi.

INTRODUCTION: Internationally validated tools to measure patient-reported health-related quality of life (HRQoL) are available, but efforts to translate and culturally validate such tools in sub-Saharan Africa (SSA) are scarce, particularly among children. METHODS: The Patient-Reported Outcomes Measurement Information System 25-item pediatric short form (PROMIS-25) assesses six HRQoL domains-mobility, anxiety, depression, fatigue, peer relationships, and pain interference-by asking four questions per domain. There is a single-item pain intensity item. The PROMIS-25 was translated into Chichewa and validated for use in Malawi using mixed qualitative and quantitative methods. The validity and reliability of the PROMIS-25 was assessed. RESULTS: Fifty-four pediatric patients with lymphoma completed the PROMIS-25. Structural validity was supported by interitem correlations and principal component analysis. Reliability of each scale was satisfactory (range alpha = 0.71-0.93). Known group validity testing showed that anemic children had worse fatigue (P = 0.016) and children with poor performance status had worse mobility (P < 0.001) and pain interference (P = 0.005). Compared to children with cancer in the United States, children from Malawi reported lower levels of mobility, higher anxiety, higher depressive symptoms, higher fatigue, better satisfaction with peer relationships, and higher pain interference. CONCLUSION: Translation and cultural validation of the PROMIS-25 into Chichewa for Malawi was successful. Baseline HRQoL for patients with pediatric lymphoma in Malawi is poor for all domains except peer relationships. This emphasizes an urgent need to address HRQoL among children undergoing cancer treatment in SSA using self-reported instruments validated within the local context.

Review of referral criteria to lipid clinics and outcomes of treatment in four UK centres.

BACKGROUND: Little data exist on the referral patterns and effectiveness of lipid clinics. METHODS: An audit was conducted in four clinics of 100 consecutive referrals each. Data were recorded on referral criteria, cardiovascular disease (CVD) risk factors, drug history, investigations, diagnoses, therapies, results and referrals. RESULTS: Patients were aged 56 ± 14 years, 47% were male and 87% were primary prevention. Risk factors included smoking (16%), type 2 diabetes (13%) and hypertension (13%). Referrals were made for hypercholesterolaemia (68%), diagnosis of FH (31%), statin intolerance (23%) and hypertriglyceridaemia (23%). Initial total cholesterol (TC) was 7.65 ± 2.64 mmol/L, triglycerides (TG) 2.17 (0.41-76.9 mmol/L) mmol/L, HDL-C 1.53 ± 0.71 mmol/L, LDL-C 4.57 ± 1.66 mmol/L with non-HDL-C 5.90 ± 2.09 mmol/L. Criteria for FH were met in 21% with genetic testing in 13% and lipid cascade testing in 30% of index cases. Triglycerides >20 mmol/L were present in 4%. The diagnosis was changed in 21%: hypercholesterolaemia (7%), mixed hyperlipidaemia (7%) and hypertriglyceridaemia (7%). Hepatic steatosis was identified in 14.5%. Lipoprotein(a) levels >125 nmol/L occurred in 41% in one clinic. Therapy changes included altered statins (40%), addition of a fibrate (11%) or ezetimibe (8%). These reduced TC by 1.92 mmol/L (19%; P = 0.0001), LDL-C 1.07 mmol/L (15%; P = 0.02), non-HDL-C 1.50 mmol/L (16%; P < 0.001), and TG 2.3 (-4 to 38) mmol/L (16%; P < 0.001) with 11% extra achieving TG <5 mmol/L while HDL-C increased by 7% (P = 0.37). CONCLUSIONS: Lipid clinics have diverse functions including diagnosis of FH, managing severe hypercholesterolaemia, mixed hyperlipidaemia and statin intolerance. Effectiveness criteria of average reductions of 1.5 mmol/L in TC or non-HDL-C, 1 mmol/L in LDL-C and 2 mmol/L in TG would be reasonable for newly referred patients.

Unknown beaked whale echolocation signals recorded off eastern New Zealand.

The echolocation signals of most beaked whale species are still unknown. In fact, out of the 22 species comprising the family Ziphiidae, only the echolocation pulses for 7 species have been clearly described. This study describes two distinct beaked whale echolocation signals recorded in the Cook Strait region using passive acoustic technology. These signals differ from previously described Ziphiid species clicks. A description of the time-frequency characteristics of the two signals is provided. Understanding the characteristics of these signals is necessary to correctly identify species from their echolocation signals and enables future monitoring of beaked whales using passive acoustics techniques.

Isolation and Identification of the Novel Tubulin Polymerization Inhibitor Bifidenone.

The pursuit of structurally novel compounds has led to the isolation of a series of neolignans (2-6), for which the structures have been determined from microgram quantities using microcryoprobe NMR technology. Compounds 2-6 provided some unexpectedly clear structure-activity relationship data, with compound 2 demonstrating significantly more potency in the in vitro cytotoxicity assay than the other analogues. Further screening found that compound 2 induces apoptosis with activation of caspase 3/7. The NCI Compare algorithm suggested that compound 2 acts through the inhibition of tubulin/microtubule dynamics. Compound 2 was confirmed to be a tubulin polymerization inhibitor that binds directly to tubulin.

CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

BACKGROUND: Research suggests that measurable change in cerebrospinal fluid (CSF) biomarkers occurs years in advance of the onset of clinical symptoms (Beckett 2010). In this review, we aimed to assess the ability of CSF tau biomarkers (t-tau and p-tau) and the CSF tau (t-tau or p-tau)/ABeta ratio to enable the detection of Alzheimer's disease pathology in patients with mild cognitive impairment (MCI). These biomarkers have been proposed as important in new criteria for Alzheimer's disease dementia that incorporate biomarker abnormalities. OBJECTIVES: To determine the diagnostic accuracy of 1) CSF t-tau, 2) CSF p-tau, 3) the CSF t-tau/ABeta ratio and 4) the CSF p-tau/ABeta ratio index tests for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease dementia or other forms of dementia at follow-up. SEARCH METHODS: The most recent search for this review was performed in January 2013. We searched MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection, including Conference Proceedings Citation Index (Thomson Reuters Web of Science), PsycINFO (OvidSP), and LILACS (BIREME). We searched specialized sources of diagnostic test accuracy studies and reviews. We checked reference lists of relevant studies and reviews for additional studies. We contacted researchers for possible relevant but unpublished data. We did not apply any language or data restriction to the electronic searches. We did not use any methodological filters as a method to restrict the search overall. SELECTION CRITERIA: We selected those studies that had prospectively well-defined cohorts with any accepted definition of MCI and with CSF t-tau or p-tau and CSF tau (t-tau or p-tau)/ABeta ratio values, documented at or around the time the MCI diagnosis was made. We also included studies which looked at data from those cohorts retrospectively, and which contained sufficient data to construct two by two tables expressing those biomarker results by disease status. Moreover, studies were only selected if they applied a reference standard for Alzheimer's disease dementia diagnosis, for example, the NINCDS-ADRDA or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. DATA COLLECTION AND ANALYSIS: We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies, and the full papers for eligibility. Two independent assessors performed data extraction and quality assessment. Where data allowed, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic (ROC) curve. MAIN RESULTS: In total, 1282 participants with MCI at baseline were identified in the 15 included studies of which 1172 had analysable data; 430 participants converted to Alzheimer's disease dementia and 130 participants to other forms of dementia. Follow-up ranged from less than one year to over four years for some participants, but in the majority of studies was in the range one to three years. Conversion to Alzheimer's disease dementia The accuracy of the CSF t-tau was evaluated in seven studies (291 cases and 418 non-cases).The sensitivity values ranged from 51% to 90% while the specificity values ranged from 48% to 88%. At the median specificity of 72%, the estimated sensitivity was 75% (95% CI 67 to 85), the positive likelihood ratio was 2.72 (95% CI 2.43 to 3.04), and the negative likelihood ratio was 0.32 (95% CI 0.22 to 0.47).Six studies (164 cases and 328 non-cases) evaluated the accuracy of the CSF p-tau. The sensitivities were between 40% and 100% while the specificities were between 22% and 86%. At the median specificity of 47.5%, the estimated sensitivity was 81% (95% CI: 64 to 91), the positive likelihood ratio was 1.55 (CI 1.31 to 1.84), and the negative likelihood ratio was 0.39 (CI: 0.19 to 0.82).Five studies (140 cases and 293 non-cases) evaluated the accuracy of the CSF p-tau/ABeta ratio. The sensitivities were between 80% and 96% while the specificities were between 33% and 95%. We did not conduct a meta-analysis because the studies were few and small. Only one study reported the accuracy of CSF t-tau/ABeta ratio.Our findings are based on studies with poor reporting. A significant number of studies had unclear risk of bias for the reference standard, participant selection and flow and timing domains. According to the assessment of index test domain, eight of 15 studies were of poor methodological quality.The accuracy of these CSF biomarkers for 'other dementias' had not been investigated in the included primary studies. Investigation of heterogeneity The main sources of heterogeneity were thought likely to be reference standards used for the target disorders, sources of recruitment, participant sampling, index test methodology and aspects of study quality (particularly, inadequate blinding).We were not able to formally assess the effect of each potential source of heterogeneity as planned, due to the small number of studies available to be included. AUTHORS' CONCLUSIONS: The insufficiency and heterogeneity of research to date primarily leads to a state of uncertainty regarding the value of CSF testing of t-tau, p-tau or p-tau/ABeta ratio for the diagnosis of Alzheimer's disease in current clinical practice. Particular attention should be paid to the risk of misdiagnosis and overdiagnosis of dementia (and therefore over-treatment) in clinical practice. These tests, like other biomarker tests which have been subject to Cochrane DTA reviews, appear to have better sensitivity than specificity and therefore might have greater utility in ruling out Alzheimer's disease as the aetiology to the individual's evident cognitive impairment, as opposed to ruling it in. The heterogeneity observed in the few studies awaiting classification suggests our initial summary will remain valid. However, these tests may have limited clinical value until uncertainties have been addressed. Future studies with more uniformed approaches to thresholds, analysis and study conduct may provide a more homogenous estimate than the one that has been available from the included studies we have identified.

Psychosocial effects of an Ebola outbreak at individual, community and international levels.

The 2013-2016 Ebola outbreak in Guinea, Liberia and Sierra Leone was the worst in history with over 28,000 cases and 11,000 deaths. Here we examine the psychosocial consequences of the epidemic. Ebola is a traumatic illness both in terms of symptom severity and mortality rates. Those affected are likely to experience psychological effects due to the traumatic course of the infection, fear of death and experience of witnessing others dying. Survivors can also experience psychosocial consequences due to feelings of shame or guilt (e.g. from transmitting infection to others) and stigmatization or blame from their communities. At the community level, a cyclical pattern of fear occurs, with a loss of trust in health services and stigma, resulting in disruptions of community interactions and community break down. Health systems in affected countries were severely disrupted and overstretched by the outbreak and their capacities were significantly reduced as almost 900 health-care workers were infected with Ebola and more than 500 died. The outbreak resulted in an increased need for health services, reduced quality of life and economic productivity and social system break down. It is essential that the global response to the outbreak considers both acute and long-term psychosocial needs of individuals and communities. Response efforts should involve communities to address psychosocial need, to rebuild health systems and trust and to limit stigma. The severity of this epidemic and its long-lasting repercussions should spur investment in and development of health systems.

La flambée de maladie à virus Ebola qui a frappé la Guinée, le Libéria et la Sierra Leone en 2013-2016 a été la pire de toute l'histoire, avec plus de 28 000 cas et 11 000 décès. Dans ce dossier, nous examinons les conséquences psychosociales de cette flambée épidémique. La maladie à virus Ebola est une maladie traumatisante, compte tenu à la fois de la gravité de ses symptômes et des taux de mortalité qui y sont associés. Les personnes affectées sont susceptibles de développer des troubles psychologiques à cause de l'évolution traumatisante de l'infection, de la peur de mourir et du fait de voir d'autres personnes mourir autour d'eux. Les survivants peuvent aussi avoir des séquelles psychologiques liées à un sentiment de honte ou de culpabilité (pour avoir transmis l'infection à d'autres personnes, par exemple) ou à cause de leur stigmatisation ou de leur mise en accusation au sein de leur communauté. À l'échelle communautaire, un schéma cyclique de peur intervient, avec une perte de confiance envers les services de santé, et la stigmatisation des personnes affectées entraîne une rupture des interactions au sein de la communauté et une fracture de la communauté. Dans les pays touchés, les systèmes de santé ont été lourdement ébranlés et même dépassés par la flambée de la maladie. Leur capacité s'est considérablement réduite, près de 900 agents de santé ont été infectés et plus de 500 sont décédés. Cette flambée épidémique a majoré les besoins de services de santé, réduit la qualité de vie et la productivité économique et entraîné la fracture du système social. La réponse internationale doit absolument tenir compte aussi bien des besoins psychosociaux immédiats des individus et des communautés que de ceux à plus long terme. Il serait judicieux que les communautés soient intégrées dans les efforts de riposte pour répondre aux besoins psychosociaux, reconstruire les systèmes de santé, rétablir la confiance des populations et limiter les stigmatisations. La gravité de cette flambée épidémique ainsi que ses répercussions durables devraient inciter à investir dans les systèmes de santé et à les consolider.

El brote de Ebola en 2013 y 2016 en Guinea, Liberia y Sierra Leona fue el peor de la historia, con más de 28 000 casos y 11 000 muertes. En este artículo se examinan las consecuencias psicosociales de la epidemia. El Ebola es una enfermedad traumática, tanto por la gravedad de sus síntomas como por las tasas de mortalidad. Los afectados pueden sufrir efectos psicológicos dado el proceso traumático de la infección, temer a la muerte y ser testigos de la muerte de otros. Los supervivientes también pueden sufrir consecuencias psicosociales debido a los sentimientos de vergüenza y culpa (por ejemplo, por transmitir la infección a otros) y la estigmatización o reproche de sus comunidades. A nivel comunitario, se produce un patrón cíclico de temor que se traduce en la pérdida de la confianza en los servicios sanitarios, lo que da lugar a la interrupción de las interacciones de las comunidades y una ruptura de las mismas. Los sistemas sanitarios de los países afectados se vieron gravemente perjudicados y desbordados por el brote, y sus capacidades se redujeron significativamente, puesto que casi 900 trabajadores sanitarios fueron infectados por el virus del Ebola y más de 500 murieron. El brote provocó una mayor necesidad de servicios de salud, redujo la calidad de vida y la productividad económica y fracturó el sistema social. Es fundamental que la respuesta mundial al brote tenga en cuenta las profundas necesidades psicosociales a largo plazo, tanto para individuos como para comunidades. Las medidas de respuesta deberían comportar que las comunidades abordasen las necesidades psicosociales, reconstruyesen los sistemas sanitarios y la confianza y redujesen la estigmatización. La gravedad de esta epidemia y sus repercusiones a largo plazo deberían estimular la inversión y el desarrollo de los sistemas sanitarios.