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The Deep Eutectic Solvents/Systems (DESs) choline chloride:urea (xChCl = 0.33) and choline chloride:glycolic acid (xChCl = 0.5) were investigated using viscosity-corrected 35Cl NMR spectroscopy and molecular dynamics simulations to probe the role of chloride as a function of water content. Three Cl- solvation regimes are revealed, with high-symmetry environments for pure and highly dilute DES, and an unusual low-symmetry interstitial region where the primary coordination sphere is most disordered.

This work is a result of GAB PhD studies for which the Brazilian National Council for Scientific and Technological Development (https://www.gov.br/cnpq/pt-br) granted scholarship number 208203/2014-1 through the Science without borders programme. The population of humpback whales (Megaptera novaeangliae) wintering off eastern South America was exploited by commercial whaling almost to the point of extinction in the mid-twentieth century. Since cessation of whaling in the 1970s it is recovering, but the timing and level of recovery is uncertain. We implemented a Bayesian population dynamics model describing the population’s trajectory from 1901 and projecting it to 2040 to revise a previous population status assessment that used Sampling-Importance-Resampling in a Bayesian framework. Using our alternative method for model fitting (Markov chain Monte Carlo), which is more widely accessible to ecologists, we replicate a “base case scenario” to verify the effect on model results, and introduce additional data to update the status assessment. Our approach allowed us to widen the previous informative prior on carrying capacity to better reflect scientific uncertainty around historical population levels. The updated model provided more precise estimates for population sizes over the period considered (1901–2040) and suggests that carrying capacity (K: median 22,882, mean 22,948, 95% credible interval [CI] 22,711–23,545) and minimum population size (N1958: median 305, mean 319, 95% CI 271–444) might be lower than previously estimated (K: median 24,558, mean 25,110, 95% CI 22,791–31,118; N1958: median 503, mean 850, 95% CI 159–3,943). However, posterior 95% credible intervals of parameters in the updated model overlap those of the previous study. Our approach provides an accessible framework for investigating the status of depleted animal populations for which information is available on historical mortality (e.g., catches) and intermittent estimates of population size and/or trend. Publisher PDF

This study investigates survival and abundance of killer whales (Orcinus orca) in Norway in 1988–2019 using capture–recapture models of photo‐identification data. We merged two datasets collected in a restricted fjord system in 1988–2008 (Period 1) with a third, collected after their preferred herring prey shifted its wintering grounds to more exposed coastal waters in 2012–2019 (Period 2), and investigated any differences between these two periods. The resulting dataset, spanning 32 years, comprised 3284 captures of 1236 whales, including 148 individuals seen in both periods. The best‐supported models of survival included the effects of sex and time period, and the presence of transients (whales seen only once). Period 2 had a much larger percentage of transients compared to Period 1 (mean = 30% vs. 5%) and the identification of two groups of whales with different residency patterns revealed heterogeneity in recapture probabilities. This caused estimates of survival rates to be biased downward (females: 0.955 ± 0.027 SE, males: 0.864 ± 0.038 SE) compared to Period 1 (females: 0.998 ± 0.002 SE, males: 0.985 ± 0.009 SE). Accounting for this heterogeneity resulted in estimates of apparent survival close to unity for regularly seen whales in Period 2. A robust design model for Period 2 further supported random temporary emigration at an estimated annual probability of 0.148 (± 0.095 SE). This same model estimated a peak in annual abundance in 2015 at 1061 individuals (95% CI 999–1127), compared to a maximum of 731 (95% CI 505–1059) previously estimated in Period 1, and dropped to 513 (95% CI 488–540) in 2018. Our results indicate variations in the proportion of killer whales present of an undefined population (or populations) in a larger geographical region. Killer whales have adjusted their distribution to shifts in key prey resources, indicating potential to adapt to rapidly changing marine ecosystems., Mark–recapture models fitted to a 32‐year photo‐identification dataset suggest constant, high apparent survival rates for killer whales in Norway but reveal temporal variations in abundance and movement patterns in response to a period of ecosystem change. These results reflected variations in the proportion present of an undefined population (or populations) in a larger geographical region of the north‐eastern Atlantic. Our results show that killer whales have adjusted their distribution to shifts in key prey resources, indicating potential to adapt to rapidly changing marine ecosystems.

Oreopithecus bambolii (8.3–6.7 million years old) is the latest known hominoid from Europe, dating to approximately the divergence time of the Pan -hominin lineages. Despite being the most complete nonhominin hominoid in the fossil record, the O. bambolii skeleton IGF 11778 has been, for decades, at the center of intense debate regarding the species’ locomotor behavior, phylogenetic position, insular paleoenvironment, and utility as a model for early hominin anatomy. Here we investigate features of the IGF 11778 pelvis and lumbar region based on torso preparations and supplemented by other O. bambolii material. We correct several crucial interpretations relating to the IGF 11778 anterior inferior iliac spine and lumbar vertebrae structure and identifications. We find that features of the early hominin Ardipithecus ramidus torso that are argued to have permitted both lordosis and pelvic stabilization during upright walking are not present in O. bambolii . However, O. bambolii also lacks the complete reorganization for torso stiffness seen in extant great apes (i.e., living members of the Hominidae), and is more similar to large hylobatids in certain aspects of torso form. We discuss the major implications of the O. bambolii lower torso anatomy and how O. bambolii informs scenarios of hominoid evolution.

Post-secondary education serves as a transition between secondary education and the world of work for many individuals, including visiting international students and immigrants. These latter groups are present on campuses in the U.S. bringing varying goals and beliefs. However, little research or practice could be found to address the potential career development needs of this group. This chapter explores the role of gender, academic major, and familial influences on a sample of immigrant and international students' career development (n = 125). Participants completed STEM-specific measures of career interest and commitment. Data were analyzed for differences between Immigrant and International students, genders, and institution type, finding significant differences on four career development measures. Significant differences were also found between groups on three of the six contextual factors, and on comparisons to other diverse samples.

AimsThis meta-analysis aimed to define the perioperative risk of mortality in patients with alcoholic liver disease (ALD) undergoing extrahepatic gastrointestinal surgery.MethodsSystematic searches of Embase, Medline and CENTRAL were undertaken to identify studies reporting about patients with ALD undergoing extrahepatic gastrointestinal surgery published since database inception to January 2019. Studies were only considered if they reported on mortality as an outcome. Pooled analysis of mortality was stratified as benign and malignant surgery and specific operative procedures where feasible.ResultsOf the 2899 studies identified, only five studies met inclusion criteria, representing cholecystectomy (one study), umbilical hernia repair surgery (one study) and oesophagectomy (three studies). The total number of patients with ALD in these studies was 172. Therefore, any study on liver disease patients undergoing extrahepatic surgery that crucially included a subset with alcohol aetiology was included as a secondary analysis even though they failed to stratify mortality by underlying aetiology. The total number of studies that met this expanded inclusion criteria was 62, reporting on 37,703 patients with liver disease of which 1735 (4.5%) had a definite diagnosis of ALD. Meta-analysis of proportions of in-hospital mortality in patients with ALD undergoing upper gastrointestinal cancer surgery (oesophagectomy) was 23% [95% confidence interval (CI) 14–35%, I2 = 0%]. In-hospital mortality following oesophagectomy in liver disease patients of all aetiologies was lower, 14% (95% CI 9–21%, I2 = 41.1%).ConclusionPostoperative in-hospital mortality is high in patients with liver disease and ALD in particular. However, the currently available evidence on ALD is limited and precludes definitive conclusions on postoperative mortality risk.

The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p

Technology-assisted treatment (TAT) holds promise for innovative assessment, prevention, and treatment of substance use disorders (SUD). The widespread access to TAT makes it a potentially cost-effective and inventive option available for delivery in multiple settings. This study assessed acceptability of the web-based Therapeutic Education System (TES) in hospitalized dual diagnosis patients with SUDs and other psychiatric disorders.

Background Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM. Methods A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed. Results One randomized and nine observational studies including 2232 patients: 1551 (69%) comprised the Surg cohort, 521 (23%) the interventional NSurg group and 160 (7%) the observational NSurg group. A significantly higher overall survival (OS) was observed when Surg was compared to interventional NSurg at 1 year (Surg 88%, 310/352; interventional NSurg 64%, 245/383; odds ratio (OR) 2.77 (confidence interval (CI) 1.94-3.97), P = 0.001), at 3 years (Surg 59%, 857/1444; interventional NSurg 26%, 138/521; OR 2.61 (CI 1.65-4.15), P = 0.002), at 5 years (Surg 47%, 533/1144; interventional NSurg 23%, 45/196; OR 3.24 (CI 1.42-7.39), P = 0.009) and at 10 years (Surg 27%, 306/1122; interventional NSurg 1%, 2/168; OR 15.64 (CI 1.87-130.76), P = 0.031). Surg was associated with a greater OS than observational NSurg at only 1 year (Surg 92%, 98/107; observational NSurg 83%, 133/160; OR 6.69 (CI 1.33-33.58), P = 0.037) and was similar to observational NSurg at all other OS time points. Comparable survival was observed among Surg and overall NSurg cohorts at 3- and 5-year survival in articles published within the last 3 years. Conclusions Recent evidence suggests comparable survival with Surg and NSurg modalities for CRLM, contrasting to early evidence where Surg had an improved survival. Significant selection bias contributes to this finding, prompting the need for high powered randomized controlled trials and registry data.

Deep eutectic solvents (DES) are potentially greener solvents obtained through the complexation of simple precursors which, among other applications, have been investigated in recent years for their ability to support the self-assembly of amphiphilic molecules. It is crucial to understand the factors which influence surfactant solubility and self-assembly with respect to the interaction of the surfactant molecule with the DES components. In this work, small-angle neutron scattering (SANS) has been used to investigate the micellization of cationic (CnTAB) and anionic (SDS) surfactants in a ternary DES comprising choline chloride, urea, and glycerol, where the hydrogen bond donors are mixed in varying molar ratios. The results show that in each case either globular or rodlike micelles are formed with the degree of elongation being directly dependent on the composition of the DES. It is hypothesized that this composition dependence arises largely from the poor solubility of the counterions in the DES, especially at low glycerol content, leading to a tighter binding of the counterion to the micelle surface and giving rise to micelles with a high aspect ratio. This potential for accurate control over micelle morphology presents unique opportunities for rheology control or to develop templated syntheses of porous materials in DES, utilizing the solvent composition to tailor micelle shape and size, and hence the pore structure of the resulting material.

Introduction Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection. Methods A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting. Results Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes. Conclusion Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

NRM was supported by Colciencias (Departamento Administrativo de Ciencia, Tecnología e Innovación, Colombia), the University of St Andrews, and NAMMCO. This study investigated the oceanic drivers of sei whale (Balaenoptera borealis) distribution in the central and eastern North Atlantic, and explored how distribution may have changed over almost three decades. Cetacean sightings data were available from Icelandic, Faroese and Norwegian surveys conducted throughout the central and eastern North Atlantic during summer between 1987 and 2015. Effective strip half width was estimated from the data to take account of variation in detection probability. Spatially-referenced environmental variables used as predictors in generalised additive models of sei whale relative density included: relief-related variables seabed depth, slope and aspect; monthly-varying physical oceanographic variables sea surface temperature (SST), mixed layer depth, bottom temperature, salinity, and sea surface height anomaly (SSH); and monthly-varying biological oceanographic variables chlorophyll-a concentration and primary productivity. Preliminary analysis considered which month (March-August) in the dynamic oceanographic variables explained most variability in sei whale density. Models including all variables (“full models”) could only be run for 1998-2015 because data for several variables were missing in earlier years. “Simple models" including only relief-related variables and SST were therefore run for 1987-89, and also for 1998-2015 for comparison. The best-fitting full model for 1998-2015 retained the covariates depth, May SST, May bottom temperature, July salinity, July SSH and July primary productivity. Of these, depth, May SST and July SSH were the strongest predictors of sei whale density. In the simple models for both 1987-89 and 1998-2015, depth (especially), May SST and seabed slope were the strongest predictors of sei whale density. The highest densities of sei whales were predicted in the Irminger Sea and over the Charles-Gibbs Fracture Zone; a pattern driven by large negative SSH, deep water (>1500m) and polar-temperate SST (5-12oC). There was some inter-annual variability in predicted distribution and there appears to be a northward expansion in distribution consistent with prey species responding to ocean warming. The models could be used to predict future distribution of sei whales based on future environmental conditions predicted by climate models. Publisher PDF

The interfacial nanostructure of the three most widely-studied Deep Eutectic Solvents (DESs), choline chloride:urea (ChCl:Urea), choline chloride:ethylene glycol (ChCl:EG), and choline chloride:glycerol (ChCl:Gly) at a Pt(111) electrode has been studied as a function of applied potential and water content up to 50 wt%. Contact mode atomic force microscope (AFM) force–distance curves reveal that for all three DESs, addition of water increases the interfacial nanostructure up to ∼40 wt%, after which it decreases. This differs starkly from ionic liquids, where addition of small amounts of water rapidly decreases the interfacial nanostructure. For the pure DESs, only one interfacial layer is measured at OCP at 0.5 nm, which increases to 3 to 6 layers extending ∼5 nm from the surface at 40 or 50 wt% water. Application of a potential of ±0.25 V to the Pt electrode for the pure DESs increases the number of near surface layers to 3. However, when water is present the applied potential attenuates the steps in the force curve, which are replaced by a short-range exponential decay. This change was most pronounced for ChCl:EG with 30 wt% or 50 wt% water, so this system was probed using cyclic voltammetry, which confirms the interfacial nanostructure is akin to a salt solution.

The American Academic of Pediatrics guides pediatricians to counsel parents about how to promote their children’s cognitive, emotional, and self-regulatory development, but the extent to which pediatricians receive the training needed to do so is unknown. An online survey was distributed to members of the Association of Pediatric Program Directors. Although most respondents agreed that it was “very important” to educate residents about parenting skills, only 11% rated their program as doing so “very well.” The most frequently reported reason for not doing very well was lack of a curriculum. Residents currently learn about parenting most commonly in continuity clinic talks, are educated via lectures, and are taught most frequently by clinic preceptors. Nearly half of the respondents reported that their residents relied on self-learning about parenting behaviors. When asked which topics respondents would like covered by an evidence-based parenting curriculum, the most commonly endorsed topic was positive discipline.

Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam, consistent with the non-competitive activity and distinct binding sites of the two classes of compounds at synaptic receptors. In a brain slice preparation, zuranolone produced a sustained increase in GABA currents consistent with metabotropic trafficking of GABAA receptors to the cell surface. In vivo, zuranolone exhibited potent activity, indicating its ability to modulate GABAA receptors in the central nervous system after oral dosing by protecting against chemo-convulsant seizures in a mouse model and enhancing electroencephalogram β-frequency power in rats. Together, these data establish zuranolone as a potent and efficacious neuroactive steroid GABAA receptor positive allosteric modulator with drug-like properties and CNS exposure in preclinical models. Recent clinical data support the therapeutic promise of neuroactive steroid GABAA receptor positive modulators for treating mood disorders; brexanolone is the first therapeutic approved specifically for the treatment of postpartum depression. Zuranolone is currently under clinical investigation for the treatment of major depressive episodes in major depressive disorder, postpartum depression, and bipolar depression.

The COVID-19 viral pandemic exposed equity and safety culture gaps in American legal education. Legal education forms part of America’s Critical Infrastructure whose continuity is important to the economy, public safety, democracy, and the national security of the United States. To address the COVID-19 pandemic and prepare for future viral pandemics and safety risks, this article recommends law schools develop a safety culture to foster health, safety, robust educational dialogue, and equity. To guide safety-and-equity-centered decision-making and promote effective legal education during and following the COVID-19 pandemic, this article contends legal education must put health, safety, and equity first. It proposes an ethical framework for legal education that centers diversity and inclusion as the foundation of robust educational dialogue. This article’s interdisciplinary analysis of COVID-19 scientific studies recommends law schools follow the science and exercise extreme caution before convening classes in person or in a hybrid fashion. COVID-19 infection risks serious illness, long-lasting complications, and death. It has preyed on America’s inequities. African-Americans, Native Americans, Latinx Americans, older Americans, and those with certain underlying health conditions including pregnant women face higher levels of hospitalization and death from COVID-19 infection. COVID-19’s inequitable risks may separate those participating in class in person, or online, by race, ethnicity, tribe, age, and health. Law schools must ensure that during the COVID-19 health emergency, hybrid or in-person pedagogical models do not undermine diversity and inclusion that supports educational dialogue and First Amendment values. The COVID-19 pandemic underscores the imperative of putting health, safety, and equity first in legal education.

Bryde’s whales (Balaenoptera edeni) are medium-sized balaenopterids with tropical and subtropical distribution. There is confusion about the number of species, subspecies and populations of Bryde’s whale found globally. Two eco-types occur off South Africa, the inshore and offshore forms, but with unknown relationship between them. Using the mtDNA control region we investigated the phylogenetic relationship of these populations to each other and other Bryde’s whale populations. Skin, baleen and bone samples were collected from biopsy-sampled individuals, strandings and museum collections. 97 sequences of 674 bp (bp) length were compared with published sequences of Bryde’s whales (n = 6) and two similar species, Omura’s (B. omurai) and sei (B. borealis) whales (n = 3). We found eight haplotypes from the study samples: H1–H4 formed a distinct, sister clade to pelagic populations of Bryde’s whales (B. brydei) from the South Pacific, North Pacific and Eastern Indian Ocean. H5–H8 were included in the pelagic clade. H1–H4 represented samples from within the distributional range of the inshore form. Pairwise comparisons of the percentage of nucleotide differences between sequences revealed that inshore haplotypes differed from published sequences of B. edeni by 4.7–5.5% and from B. brydei by 1.8–2.1%. Ten fixed differences between inshore and offshore sequences supported 100% diagnosability as subspecies. Phylogenetic analyses grouped the South African populations within the Bryde’s-sei whale clade and excluded B. edeni. Our data, combined with morphological and ecological evidence from previous studies, support subspecific classification of both South African forms under B. brydei and complete separation from B. edeni. Postprint

This manuscript presents a comparative study of the physico-chemical behaviour of sulfobetaine-type single and double zwitterions and zwitterionic salts, and structurally similar mono- and di-cationic tetraalkylammonium salts in aqueous solutions. The study includes experimental determination of the density and viscosity of highly diluted aqueous solutions with derivation of the Jones-Dole viscosity B-coefficient, partial molal volumes at infinite dilution, and hydration numbers. The study also examines the effects of addition of the salts on the surface tension of cationic and anionic surfactants, upper critical solution temperature of a non-ionic surfactant, solubility of amino acids, and stability of a protein. The experimental investigation was performed taking a broad bottom-up approach with the aim to elucidate the effect of molecular architecture and charge (two versus four) on the degree of surface hydration of a molecule, kosmotropicity, and interactions with charged and hydrophilic/hydrophobic surfaces - all-important characteristics which define ability of a functional group to resist protein attachment. The novel multicharged zwitterionic materials have exhibited superior qualities, thus paving the way to development of a new platform in design of hydrophilic and anti-fouling surfaces by employing the four-charge bearing molecular motifs.

The postpartum hospital stay is a unique opportunity for clinicians to educate parents on the importance of promoting early child development. Pediatricians are well-positioned to address both medical and developmental concerns during critical periods of development, yet very few parenting interventions are led by pediatricians.To assess the impact of a novel one-hour long pediatrician-led Newborn Class on maternal knowledge, confidence, and anxiety.We conducted a quasi-randomized controlled trial to evaluate the effectiveness of the Newborn Class. First-time mothers who delivered a full-term singleton vaginally with no major complications and attended the class were recruited. Mothers who expressed a desire to attend the class but were discharged before a class was offered served as controls.Maternal self-perceived parental confidence and anxiety were measured using standardized scales [Karitane Parenting Confidence Scale (KPCS) and State-Trait Anxiety Inventory for Adults (STAI-AD)]. Knowledge on newborn care was assessed using a novel scale.A total of 84 participants (intervention n = 36, control n = 48) were included in the study. Mothers who attended the class showed significantly higher levels of knowledge compared to the control group (Knowledge test, Two-tailed t-test, mean [SD], 8.08 [1.06] vs 6.78 [1.25]; P0.001) as well as significantly higher parenting confidence levels (KPCS, Two-tailed t-test, mean [SD], 39.31 [3.88] vs 35.20 [3.99]; P0.001). No change was observed in the overall level of anxiety (STAI-AD, Two-tailed t-test, mean [SD], 35.50 [8.73] vs 38.5 [9.53]; P=0.164).A short pediatrician-led parenting intervention may be an effective tool in improving maternal confidence and newborn care knowledge. Given the importance of the newborn period in establishing healthy developmental trajectories, there is a crucial need for cost- and time-effective intervention that can be widely implemented to promote parental knowledge and confidence with the ultimate goal of fostering healthy development in children.

The mainstay of clinical diagnostics is the use of specialised ligands that can recognise specific biomarkers relating to pathological changes. While protein antibodies have been utilised in these assays for the last 40 years, they have proven to be unreliable due to a number of reasons. The search for the ‘perfect’ targeting ligand or molecular probe has been slow, though the description of chemical antibodies, also known as aptamers, nearly 30 years ago suggested a replacement reagent. However, uptake has been slow to progress into the clinical environment. In this review, we discuss the issues associated with antibodies and describe some of the applications of aptamers that have relevancy to the clinical diagnostic environment.

GA Bortolotto PhD is funded by the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq; Science Without Borders, scholarship #208203/2014 - 1). Cetacean International Society granted GA Bortolotto with small grants which contributed to the development of this study. The western South Atlantic humpback whale population was severely depleted by commercial whaling in the late 19th and 20th centuries, and today inhabits a human-impacted environment in its wintering grounds off the Brazilian coast. We identified distribution patterns related to environmental features and provide new estimates of population size, which can inform future management actions. We fitted spatial models to line transect data from 2 research cruises conducted in 2008 and 2012 to investigate (1) habitat use and (2) abundance of humpback whales wintering in the Brazilian continental shelf. Potential explanatory variables were year, depth, seabed slope, sea-surface temperature (SST), northing and easting, current speed, wind speed, distance to coastline and to the continental shelf break, and shelter (a combination of wind speed and SST categories). Whale density was higher in slower currents, at shorter distances to both the coastline and shelf break, and at SSTs between 24 and 25°C. The distribution of whales was also strongly related to shelter. For abundance estimation, easting and northing were included in the model instead of SST; estimates were 14264 whales (CV = 0.084) for 2008 and 20389 (CV = 0.071) for 2012. Environmental variables explained well the variation in whale density; higher density was found to the south of the Abrolhos Archipelago, and shelter seems to be important for these animals in their breeding area. Estimated distribution patterns presented here can be used to mitigate potential human-related impacts, such as supporting protection in the population’s core habitat near the Abrolhos Archipelago. Postprint

Dravet syndrome is an infant-onset epileptic encephalopathy with multiple seizure types that are often refractory to conventional therapies. Treatment with standard benzodiazepines like clobazam, in combination with valproate and stiripentol, provides only modest seizure control. While benzodiazepines are a first-line therapy for Dravet syndrome, they are limited by their ability to only modulate synaptic receptors. Unlike benzodiazepines, neuroactive steroids potentiate a wider-range of GABAA receptors. The synthetic neuroactive steroid SGE-516 is a potent positive allosteric modulator of both synaptic and extrasynaptic GABAA receptors. Prior work demonstrated anticonvulsant activity of SGE-516 in acute seizure assays in rodents. In this study, we evaluated activity of SGE-516 on epilepsy phenotypes in the Scn1a+/− mouse model that recapitulates many features of Dravet syndrome, including spontaneous seizures, premature death and seizures triggered by hyperthermia. To evaluate SGE-516 in Scn1a+/− mice, we determined the effect of treatment on hyperthermia-induced seizures, spontaneous seizure frequency and survival. SGE-516 treatment protected against hyperthermia-induced seizures, reduced spontaneous seizure frequency and prolonged survival in the Scn1a+/− mice. This provides the first evidence of SGE-516 activity in a mouse model of Dravet syndrome, and supports further investigation of neuroactive steroids as potential anticonvulsant compounds for refractory epilepsies.

The work was funded by the Pew Marine Fellows Program and WCS. 1. Many species and populations of marine megafauna are undergoing substantial declines, while many are also very poorly understood. Even basic information on species presence is unknown for tens of thousands of kilometres of coastline, particularly in the developing world, which is a major hurdle to their conservation. 2. Rapid ecological assessment is a valuable tool used to identify and prioritize areas for conservation; however, this approach has never been clearly applied to marine cetaceans. Here a rapid assessment protocol is outlined that will generate broad‐scale, quantitative, baseline data on cetacean communities and potential threats, that can be conducted rapidly and cost-effectively across whole countries, or regions. 3. The rapid assessment was conducted in Tanzania, East Africa, and integrated collection of data on cetaceans from visual, acoustic, and interview surveys with existing information from multiple sources, to provide low resolution data on cetacean community relative abundance, diversity, and threats. Four principal threats were evaluated and compared spatially using a qualitative scale: cetacean mortality in fishing gear (particularly gillnets); cetacean hunting, consumption or use by humans; shipping related collision risk and noise disturbance; and dynamite fishing. 4. Ninety‐one groups of 11 species of marine mammal were detected during field surveys. Potentially the most important area for cetaceans was the Pemba Channel, a deep, high‐current waterway between Pemba Island and mainland Africa, where by far the highest relative cetacean diversity and high relative abundance were recorded, but which is also subject to threats from fishing. 5. A rapid assessment approach can be applied in data deficient areas to quickly provide information on cetaceans that can be used by governments and managers for marine spatial planning, management of developments, and to target research activities into the most important locations. Postprint

Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11–71.4, P < 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12–2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection in children who slept closest to a case who smoked within the same home compared with a nonsmoking case (OR: 8.0 [95% CI: 2.74–23.29] versus 2.4 [95% CI: 1.17–4.92], P < 0.001). SHS exposure as an effect modifier appears to greatly increase the risk of M. tuberculosis infection in children exposed to PTB cases. Smoking cessation campaigns may be important for reducing transmission of M. tuberculosis to children within households.

We present the first demonstration of a general method for the chemical characterization of small surface features at high magnification via simultaneous collection of mass spectrometry (MS) imaging and tandem MS imaging data. High lateral resolution tandem secondary ion MS imaging is employed to determine the composition of surface features on poly(ethylene terephthalate) (PET) that precipitate during heat treatment. The surface features, probed at a lateral resolving power of

Despite the availability of multiple antiepileptic drugs (AED), failure to adequately control seizures is a challenge for approximately one third of epilepsy patients, and new therapies with a differentiated mechanism of action are needed. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors. As a neuroactive steroid, SGE-516 has pharmacokinetic properties that are intended to allow for chronic oral dosing. We investigated the anticonvulsant activity of SGE-516 across numerous in vitro and in vivo models of seizure activity. SGE-516 dose-dependently reduced neuronal firing rates and epileptiform activity in vitro. In mice, SGE-516 protected against acute seizures in the PTZ-induced chemo-convulsant seizure model and the 6Hz psychomotor seizure model. In addition, SGE-516 demonstrated anticonvulsant activity in the mouse corneal kindling model. These data suggest that SGE-516 may have potential for development as a novel oral AED for the treatment of refractory seizures.

Orientation of the iliac blades is a key feature that appears to distinguish extant apes from monkeys. Iliac morphology is hypothesized to reflect variation in thoracic shape that, in turn, reflects adaptations for shoulder and forearm function in anthropoids. Iliac orientation is traditionally measured relative to the acetabulum, whereas functional explanations pertain to its orientation relative to the cardinal anatomical planes. We investigated iliac orientation relative to a median plane using digital models of hipbones registered to landmark data from articulated pelves. We fit planes to the iliac surfaces, midline, and acetabulum, and investigated linear metrics that characterize geometric relationships of the iliac margins. Our results demonstrate that extant hominoid ilia are not rotated into a coronal plane from a more sagittal position in basal apes and monkeys but that the apparent rotation is the result of geometric changes within the ilia. The whole ilium and its gluteal surface are more coronally oriented in apes, but apes and monkeys do not differ in orientation of the iliac fossa. The angular differences in the whole blade and gluteal surface primarily reflect a narrower iliac tuberosity set closer to the midline in extant apes, reflecting a decrease in erector spinae muscle mass associated with stiffening of the lumbar spine. Mediolateral breadth across the ventral dorsal iliac spines is only slightly greater in extant apes than in monkeys. These results demonstrate that spinal musculature and mobility have a more significant effect on pelvic morphology than does shoulder orientation, as had been previously hypothesized. Anat Rec, 300:810-827, 2017. © 2017 Wiley Periodicals, Inc.

In the present work we show how to achieve different nanotube morphologies (namely, not only single- and double-walled tubes, but also a tube-in-tube configuration) by combining specific anodization parameters. We characterize as-grown tube layers in terms of morphology, chemical composition and properties. As-grown tubes exhibit a double-walled morphology, that is, they consist of an inner and an outer shell. The low quality inner shell can be removed by an optimized chemical treatment thus leading to nanotubes of a higher quality oxide and with a single-walled nature. Double-walled tubes grown at low electrolyte temperature provide a thick inner shell that after adequate annealing can form a unique tube-in-tube morphology.

Organophosphorus nerve agents (OPNAs) are irreversible inhibitors of acetylcholinesterase that pose a serious threat to public health because of their use as chemical weapons. Exposure to high doses of OPNAs can dramatically potentiate cholinergic synaptic activity and cause status epilepticus (SE). Current standard of care for OPNA exposure involves treatment with cholinergic antagonists, oxime cholinesterase reactivators, and benzodiazepines. However, data from pre-clinical models suggest that OPNA-induced SE rapidly becomes refractory to benzodiazepines. Neuroactive steroids (NAS), such as allopregnanolone, retain anticonvulsant activity in rodent models of benzodiazepine-resistant SE, perhaps because they modulate a broader variety of GABAA receptor subtypes. SGE-516 is a novel, next generation NAS and a potent and selective GABAA receptor positive allosteric modulator (PAM). The present study first established that SGE-516 reduced electrographic seizures in the rat lithium-pilocarpine model of pharmacoresistant SE. Then the anticonvulsant activity of SGE-516 was investigated in the soman-intoxication model of OPNA-induced SE. SGE-516 (5.6, 7.5, and 10 mg/kg, IP) significantly reduced electrographic seizure activity compared to control when administered 20 min after SE onset. When 10 mg/kg SGE-516 was administered 40 min after SE onset, seizure activity was still significantly reduced compared to control. In addition, all cohorts of rats treated with SGE-516 exhibited significantly reduced neuronal cell death as measured by FluoroJade B immunohistochemistry. These data suggest synthetic NASs that positively modulate both synaptic and extrasynaptic GABAA receptors may be candidates for further study in the treatment of OPNA-induced SE.

Research on the processes of change in career development has focused on developmental stages rather than processes. This manuscript reports on the development and validation of the stages of change—career development scale, adapted from McConnaughy, Prochaska, & Velicer (1983) measure of stages of change in psychotherapy. Data from 875 postsecondary students were analyzed using exploratory and confirmatory factor analysis, resulting in a 15-item measure with five factors. Convergent and divergent validity was demonstrated, suggesting that this scale has the potential to explicate the process of change in ways that will be useful to research and practice.