Paleoamerican exploitation of extinct megafauna revealed through immunological blood residue and microwear analysis, North and South Carolina, USA.

Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points.

'I wish I had asked for support earlier' - Immigrant family caregivers' experiences of living with a person with dementia.

Introduction: Immigrant family caregivers are increasing worldwide, likewise the number of older people with dementia. Caring for a person with dementia is demanding, with the carer's own life put on hold. Immigrant family caregivers have been less studied.

Statistical methodology for highly variable compounds: A novel design approach for the ofatumumab Phase 2 bioequivalence study.

This article describes a novel mixed-scaling testing strategy, in combination with an adaptive parallel-groups bioequivalence trial, to test pharmacokinetic equivalence of two formulations of a drug with highly variable pharmacokinetics. The methodology was applied to the Phase 2 APLIOS study in relapsing multiple sclerosis patients, where the bioequivalence of subcutaneous ofatumumab 20 mg administered via an autoinjector pen (test formulation) versus prefilled syringe (reference formulation) in the abdomen has been studied. Due to a high coefficient of variation (CV) of the relevant pharmacokinetic metrics (AUC and C ) for the reference formulation (>30%), a reference-Scaled bioequivalence (RSABE) approach was applied but modified for a parallel-groups design.

Improving pediatric multiple sclerosis interventional phase III study design: a meta-analysis.

Background: To support innovative trial designs in a regulatory setting for pediatric-onset multiple sclerosis (MS), the study aimed to perform a systematic literature review and meta-analysis of relapse rates with interferon β (IFN β), fingolimod, and natalizumab and thereby demonstrate potential benefits of Bayesian and non-inferiority designs in this population.

Methods: We conducted a literature search in MEDLINE and EMBASE from inception until 17 June 2020 of all studies reporting annualized relapse rates (ARR) in IFN β-, fingolimod-, or natalizumab-treated patients with pediatric-onset relapsing-remitting MS. These interventions were chosen because the literature was mainly available for these treatments, and they are currently used for the treatment of pediatric MS.

Dispelling myths: The case for women in radiology and radiation oncology.

Common misconceptions about radiology and radiation oncology exist and may dissuade women from pursuing these specialties. The American Association for Women in Radiology (AAWR) Medical Student Outreach Subcommittee began a multi-year social media campaign aimed at addressing these myths. Here, we outline several myths presented in this social media campaign and provide a combination of literature review and experts' opinions to deconstruct and dispel them.

Ofatumumab versus Teriflunomide in Multiple Sclerosis.

Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.

Pharmacological inhibition of P2RX7 ameliorates liver injury by reducing inflammation and fibrosis.

Extracellular adenosine triphosphate (eATP) released by damaged cells, and its purinergic receptors, comprise a crucial signaling network after injury. Purinergic receptor P2X7 (P2RX7), a major driver of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and IL-1β processing, has been shown to play a role in liver injury in murine diet- and chemically-induced liver injury models. It is unclear, however, whether P2RX7 plays a role in non-alcoholic steatohepatitis (NASH) and which cell type is the main target of P2RX7 pharmacological inhibition.

The role of firearms in intimate partner violence: policy and research considerations.

Intimate partner violence (IPV) is a major threat to women's safety and well-being worldwide. Firearms heighten this threat by increasing the morbidity and mortality of IPV. This paper focuses on the United States, a nation with high rates of IPV alongside high rates of gun ownership.

Sediment Cores from White Pond, South Carolina, contain a Platinum Anomaly, Pyrogenic Carbon Peak, and Coprophilous Spore Decline at 12.8 ka.

A widespread platinum (Pt) anomaly was recently documented in Greenland ice and 11 North American sedimentary sequences at the onset of the Younger Dryas (YD) event (~12,800 cal yr BP), consistent with the YD Impact Hypothesis. We report high-resolution analyses of a 1-meter section of a lake core from White Pond, South Carolina, USA. After developing a Bayesian age-depth model that brackets the late Pleistocene through early Holocene, we analyzed and quantified the following: (1) Pt and palladium (Pd) abundance, (2) geochemistry of 58 elements, (3) coprophilous spores, (4) sedimentary organic matter (OC and sedaDNA), (5) stable isotopes of C (δC) and N (δN), (6) soot, (7) aciniform carbon, (8) cryptotephra, (9) mercury (Hg), and (10) magnetic susceptibility.

Fast versus gradual adaptation of soft daily disposable contact lenses in neophyte wearers.

Purpose: Despite the widespread practice of gradually adapting all new soft contact lens wearers (neophytes), there is little evidence-based research underpinning such practice. This work determined if a gradual adaptation period is necessary for neophytes when fitted with modern hydrogel or silicone-hydrogel daily disposable contact lenses.

Method: At four sites, neophytes (19-32 years) were randomly assigned to an adaptation schedule: fast (10 h wear from the first day) or gradual (4 h on the first day, increasing their wear-time by 2 h on each subsequent day until they had reached 10 h) with hydrogel (n = 24 fast; n = 21 gradual) or silicone-hydrogel (n = 10 fast; n = 10 gradual) contact lenses.

Highly Diastereoselective Synthesis of a HCV NS5B Nucleoside Polymerase Inhibitor.

An asymmetric synthesis of HCV NS5B nucleoside polymerase inhibitor (1) is described. This novel route features several remarkably diastereoselective and high-yielding transformations, including construction of the all-carbon quaternary stereogenic center at C-2 via a thermodynamic aldol reaction. A subsequent glycosylation reaction with activated uracil via C-1 phosphate and installation of the cyclic phosphate group using an achiral phosphorus(III) reagent followed by oxidation provides 1.

Widespread platinum anomaly documented at the Younger Dryas onset in North American sedimentary sequences.

Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.).

Overvaluation of shape and weight in adolescents with anorexia nervosa: does shape concern or weight concern matter more for treatment outcome?

Background: Overvaluation of shape and weight is a key diagnostic feature of anorexia nervosa (AN); however, limited research has evaluated the clinical utility of differentiating between weight versus shape concerns. Understanding differences in these constructs may have important implications for AN treatment given the focus on weight regain. This study examined differences in treatment outcome between individuals whose primary concern was weight versus those whose primary concern was shape in a randomized controlled trial of treatment for adolescent AN.

Picking and nibbling in children and adolescents with eating disorders.

Objective: Picking and nibbling (P&N), defined as eating in an unplanned and repetitious way between meals and snacks, is prevalent among adults with eating disorders (EDs), but unexamined among youth with EDs. This study sought to assess the prevalence of P&N in youth with EDs and its association with ED and comorbid pathology.

Method: Youth (N = 515; ages 7-18) who presented to one outpatient ED research-clinical program were assessed for ED and comorbid pathology.

Bayesian chronological analyses consistent with synchronous age of 12,835-12,735 Cal B.P. for Younger Dryas boundary on four continents.

The Younger Dryas impact hypothesis posits that a cosmic impact across much of the Northern Hemisphere deposited the Younger Dryas boundary (YDB) layer, containing peak abundances in a variable assemblage of proxies, including magnetic and glassy impact-related spherules, high-temperature minerals and melt glass, nanodiamonds, carbon spherules, aciniform carbon, platinum, and osmium. Bayesian chronological modeling was applied to 354 dates from 23 stratigraphic sections in 12 countries on four continents to establish a modeled YDB age range for this event of 12,835-12,735 Cal B.P.

Telemedicine of family-based treatment for adolescent anorexia nervosa: A protocol of a treatment development study.

Background: Family-based treatment is an efficacious treatment available for adolescents with anorexia nervosa. Yet the implementation of this treatment, at least in the United States, is challenging due to a limited number of trained family-based treatment therapists and the concentration of these therapists in a limited number of urban centers. The use of telemedicine in the delivery of family-based treatment can increase access to this therapy for this patient population.

A Burkholderia pseudomallei colony variant necessary for gastric colonization.

Unlabelled: Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow colony variants (YA and YB).

Optimization of murine small intestine leukocyte isolation for global immune phenotype analysis.

New efforts to understand complex interactions between diet, gut microbiota, and intestinal immunity emphasize the need for a standardized murine protocol that has been optimized for the isolation of lamina propria immune cells. In this study multiple mouse strains including BALB/c, 129S6/Sv/EvTac and ICR mice were utilized to develop an optimal protocol for global analysis of lamina propria leukocytes. Incubation temperature was found to significantly improve epithelial cell removal, while changes in media formulation had minor effects.

Utilizing reamer irrigator aspirator (RIA) autograft for opening wedge high tibial osteotomy: A new surgical technique and report of three cases.

Introduction: The lateral closing wedge high tibial osteotomy (HTO) was popularized by Coventry in the 1960s. In the 1990s the medial opening wedge osteotomy gained popularity because it could achieve greater valgus correction and it did not require dissociation of the fibula from the tibia, an important consideration when treating varus knees with lateral and posterolateral ligament deficiencies (Noyes' double-varus and triple-varus knees). However, it has the disadvantage of requiring bone graft to fill bony defects.

Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine.

Infections with the Gram-negative bacterium Burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with B. pseudomallei.

An improved selective culture medium enhances the isolation of Burkholderia pseudomallei from contaminated specimens.

Burkholderia pseudomallei is a Gram-negative environmental bacterium found in tropical climates that causes melioidosis. Culture remains the diagnostic gold standard, but isolation of B. pseudomallei from heavily contaminated sites, such as fecal specimens, can be difficult.

Evidence for deposition of 10 million tonnes of impact spherules across four continents 12,800 y ago.

Airbursts/impacts by a fragmented comet or asteroid have been proposed at the Younger Dryas onset (12.80 ± 0.15 ka) based on identification of an assemblage of impact-related proxies, including microspherules, nanodiamonds, and iridium.

Asymmetric synthesis of cis-2,5-disubstituted pyrrolidine, the core scaffold of β3-AR agonists.

A practical, enantioselective synthesis of cis-2,5-disubstituted pyrrolidine is described. Application of an enzymatic DKR reduction of a keto ester, which is easily accessed through a novel intramolecular N→C benzoyl migration, yields syn-1,2-amino alcohol in >99% ee and >99:1 dr. Subsequent hydrogenation of cyclic imine affords the cis-pyrrolidine in high diastereoselectivity.