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In recent years, the implementation of thin-film Ta has led to improved coherence times in superconducting circuits. Efforts to further optimize this materials set have become a focus of the subfield of materials for superconducting quantum computing. It has been previously hypothesized that grain size could be correlated with device performance. In this work, we perform a comparative grain size experiment with α -Ta on c axis sapphire. Our evaluation methods include both room-temperature chemical and structural characterization and cryogenic microwave measurements, and we report no statistical difference in device performance between smaller- and larger-grain-size devices with grain sizes of 924 and 1700 nm 2 , respectively. These findings suggest that grain size is not correlated with loss in the parameter regime of interest for Ta grown on c axis sapphire, narrowing the parameter space for optimization of this materials set. [ABSTRACT FROM AUTHOR]

The development of new medicines for systemic lupus erythematosus (SLE) has not addressed unmet clinical need, with only three drugs receiving regulatory approval for SLE in the last 60 years, one of which was specifically licensed for lupus nephritis. In the last 20 years it has become clear that activation of type 1 interferons (IFN) is reproducibly detected in the majority of SLE patients, and the actions of IFN in the immune system and on target tissues is consistent with a pathogenic role in SLE. These findings led to considerable drug discovery activity, first with agents directly targeting IFN family cytokines, with results that were encouraging but underwhelming. In contrast, targeting the type I IFN receptor with the monoclonal antibody anifrolumab, thereby blocking all IFN family members, was effective in a phase II clinical trial. This led to a pair of phase III trials, one of which was negative and the other positive, reflecting the difficulty of obtaining outcomes from trials in this complex disease. Nonetheless, the balance of evidence resulted in approval of anifrolumab in multiple jurisdictions from 2021 onwards. Multiple approaches to targeting the type 1 IFN pathway have subsequently had positive phase II clinical trials, including antibodies targeting cells that produce IFN, and small molecules targeting the receptor kinase TYK2, required for IFN signalling. Despite multiple hurdles, it is clear that IFN targeting in SLE is here to stay. The story of IFN-targeting therapy in SLE has lessons for drug development overall in this disease. [ABSTRACT FROM AUTHOR]

Introduction Methods Consumer and Community Involvement Results Conclusion The Sensory Processing Measure 2 (SPM2) and the Sensory Profile 2 (SP2) are two sensory processing scales often used by occupational therapists. The SPM2 and SP2 both claim to assess aspects of children's sensory processing. This cross‐sectional study examined the convergent validity of the SPM2‐Home Form (SPM2‐HF) and Child SP2 for school‐aged neurotypical children.Thirty parents/caregivers of neurotypical children aged 7 to 12 completed the SPM2‐HF and the Child SP2 about their child. Spearman rho's correlation coefficient with bootstrapping was used to investigate the correlations among the sensory, behavioural, and quadrant scores of the Child SP2 and SPM2‐HF subscale scores.Given the topic, consumers and community members were not involved in the design, execution, or write up of the study results.Several statistically significant correlations were found between the sensory and quadrant subscales of the Child SP2 with the SPM‐HF. Strong to moderate correlations were established between the sensory subscales of the Child SP2 and the SPM2‐HF, ranging from 0.40 to 0.74 (p < 0.05). Additionally, correlations between the quadrant subscales of the Child SP2 and the subscales of the SPM2‐HF ranged from weak (0.38) to strong (0.77) correlations (p < 0.05).These results provide evidence of convergent validity between the SPM2‐HF and Child SP2 for neurotypical school‐aged children. Further research on the psychometric properties of the SPM2‐HF and Child SP2 is recommended. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of different food residues on the recovery of Listeria monocytogenes and Salmonella Typhimurium from stainless steel surfaces. Food residues tested include lettuce rinsate, blended lettuce, low-fat milk, and whole milk for Listeria monocytogenes, and powdered infant formula, all-purpose flour, and whole milk dairy powder for Salmonella Typhimurium. Bacterial suspensions were inoculated on stainless steel surfaces with or without food residues and held for different time periods. Significant differences (P < 0.0001) in Salmonella Typhimurium recovery were observed between the no food residue control and all food residues over 24 hours. For Listeria monocytogenes, minimal variability in recovery was observed among food residue types, with significant differences from the no food residue control (P < 0.05) observed after 24 hours. The study also found that surface sampling can spread Listeria monocytogenes and Salmonella Typhimurium on stainless steel surfaces, suggesting that food residue type may affect microbial recovery during environmental monitoring. [ABSTRACT FROM AUTHOR]

Training in infant observation, highly valuable in the infant mental health (IMH) field, has an enormous amount to offer family therapists. These two fields of practice, both hold working with the relational world of their clients as central. As two senior family therapists who are also IMH practitioners, we invite those reading this paper to explore the possibilities inherent in undertaking infant observation training as a pathway to enriching and expanding their practice. We provide an overview of infant observation training, how this approach was conceived, and explore the benefits of honouring the subjectivity of the infant, that of bringing the infant's experience alive in the therapeutic space. We provide direct examples from our own practice. We conclude with how infant observation might be incorporated into family therapy training and practice. [ABSTRACT FROM AUTHOR]

The development of machine learning (ML) predictors does not necessarily require the employment of expansive classifiers and complex feature encoding schemes to achieve the highest accuracy scores. It rather requires data pre-processing, feature optimization, and robust evaluation to ensure consistent results and generalizability. Herein, we describe a multi-stage process to develop a reliable ML predictor of cell penetrating peptides (CPPs). We emphasize the challenges of: (i) the generation of representative datasets with all required pre-processing procedures; (ii) comprehensive and exclusive encoding of peptides using their amino acid composition; (iii) obtaining an optimized feature set using a simple classifier (support vector machine, SVM); (iv) ensuring consistent results; and (v) verifying generalizability at the highest achievable accuracy scores. Two peptide sub-spaces were used to generate the negative examples, which are required, along with the known CPPs, to train the classifier. These included: (i) randomly generated peptides with all amino acid types being equally represented and (ii) extracted peptides from receptor proteins. Results indicated that the randomly generated dataset performed perfectly well within its own peptide sub-space, while it poorly generalized to the other sub-space. Conversely, the dataset extracted from receptor proteins, while achieving lower accuracies, showed a perfect generalizability to the other peptide sub-space. We combined the qualities of these two datasets by utilizing the average of their predictions within our ultimate framework. This functional ML predictor, WLVCPP, and associated software and datasets can be downloaded from https://github.com/BahaaIsmail/WLVCPP. Testing machine learning predictors of cell penetrating peptides against new peptide candidates is often disappointing, despite the use of sophisticated classifiers and complex feature encoding schemes. The unrepresentativeness of used datasets, ill-conditioned data, redundant feature sets, and deficient evaluation procedures commonly lead to inconsistent results and ungeneralizable models. Accordingly, we propose a holistic strategy to negate sources of error to obtain a stable, consistent, accurate, and generalizable model. [ABSTRACT FROM AUTHOR]

Djeya1 (RKLAFRYRRIKELYNSYR) is a very effective cell penetrating peptide (CPP) that mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species-variable sites: 10, 13, and 16. CD analyses indicated that Djeya1 is highly helical, and that Aib-substitution had subtle influences upon the secondary structures of bioengineered analogues. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells, a prostate cancer line that expresses high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblasts are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation. [ABSTRACT FROM AUTHOR]

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve. [ABSTRACT FROM AUTHOR]

While economic inequality continues to rise within countries, efforts to address it have been largely ineffective, particularly those involving behavioral approaches. It is often implied but not tested that choice patterns among low-income individuals may be a factor impeding behavioral interventions aimed at improving upward economic mobility. To test this, we assessed rates of ten cognitive biases across nearly 5000 participants from 27 countries. Our analyses were primarily focused on 1458 individuals that were either low-income adults or individuals who grew up in disadvantaged households but had above-average financial well-being as adults, known as positive deviants. Using discrete and complex models, we find evidence of no differences within or between groups or countries. We therefore conclude that choices impeded by cognitive biases alone cannot explain why some individuals do not experience upward economic mobility. Policies must combine both behavioral and structural interventions to improve financial well-being across populations. [ABSTRACT FROM AUTHOR]

Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021--February 2022. The variantspecific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period. [ABSTRACT FROM AUTHOR]

In 2020, UNLV Special Collections and Archives conducted an internal audit of collections, strategic plans, and programming in order to assess how well it is meeting strategic goals of being more inclusive and increasing diversity and representation. In a data-driven institution, how can assessment be used to advocate for resources focused on diversity, equity, and inclusion? In conducting this analysis, UNLV hoped to answer the following query: how is progress measured if the goal is to preserve stories outside the traditional narrative (white, male, cisgender, heteronormative, etc.)? This article discusses strategies for assessing diversity in special collections and archives. [ABSTRACT FROM AUTHOR]

The article discusses recognition of need of student involvement by Student Affairs Professionals (SAP) by knowledge of student development theory and mentions chance for students created by SAP for student to engage in on-campus organizations. Topics discussed include higher education not designed to focus on reduction of oppression of communities of color, issues of racialization of campus housing, and reframing involvement on colleges that take reimagining and creativity.

This article considers discussions of sexual difference in a range of popular prescriptive texts published between 1920 and 1940 in order to explore the relationship between science and American marital advice literature. It demonstrates the particular role science played in shaping, legitimising and enforcing changing discussions about what 'good sex' should look like in contemporary advice – supporting a hierarchy of sexual activities and desires that privileged a particular version of marital heterosexual expression. Through this, it also interrogates the 'popular' version of sexual science being consumed by the American public at this time. In addition to adding new perspectives to our understanding of contemporary advice and its relationship with science and medicine, it will also act as a provocation for further research into the ways the public engaged with sexual science in early twentieth‐century America. [ABSTRACT FROM AUTHOR]

Pressure ulcer (PU) prevention is a high priority for health professionals in all settings. While PU incidence is expected to rise given the ageing population in the UK and Europe, PUs can occur in people of any age. It is therefore imperative that all practitioners know about the causes and consequences of PUs and be aware of up-to-date guidance on the prevention and management in patients who have developed a PU or who are at risk of developing a PU. Health professionals should also be aware of preventive equipment highlighted in national and local guidance, prevention strategies and protocols. This article discusses these issues and the Devon (Cardinal Health) prevention and repositioning product range. [ABSTRACT FROM AUTHOR]

This article offers a close reading of Stendhal's Lamiel , arguing that the eponymous heroine suffers from, but also manipulates the symptoms of, the quintessentially nineteenth-century disease, consumption. It first establishes Lamiel as a consumptive heroine by comparing the novel to contemporary medical discourse on the disease, most notably to the work of René Laënnec. It then analyses the fausse phtisie scene, a passage in which Lamiel uses the blood of a dead bird to simulate haemoptysis, contending that the performative nature of Lamiel's illness is of primary importance. Comparing Lamiel to other Stendhal novels, the article highlights that the heroine asserts her own identity by assuming abjection, whereas other characters are threatened by the abject. It further demonstrates that this scene amounts to Lamiel's rejection of Romantic tropes of passive female patienthood, arguing that the novel forges a new mould for the representation of consumptive heroines. This article contributes to our understanding of how literature can manipulate, undermine, and even reject medical and cultural paradigms of illnesses as ubiquitous to the nineteenth century as tuberculosis. [ABSTRACT FROM AUTHOR]

The article presents an interview with American academic Loretta J. Ross on the implications of the Supreme Court overturning Roe v. Wade highlighting the new possibilities for abortion opponents and setbacks for the feminist movement. Topics include the political motivations behind the end of Roe v. Wade, the connections between reproductive justice and other social justice issues, and the need to address the economic aspects of abortion in discussions and activism.

The article focuses on the author's personal journey from anger and disillusionment within the right-wing movement to finding a home for her anger in the left and socialist feminism. Topics include the author's experience with anger and limitations imposed by the right, her exploration of feminism and socialism as alternatives, and the importance of harnessing anger for political and social change within a broader movement.

The primary aims were to (1) identify the factor structure of tests thought to measure semantic and episodic memory and (2) examine whether patterns of impairment would show a double dissociation between these two memory systems at an individual level in patients with temporal lobe epilepsy (TLE). The secondary aim was to explore the impact of epilepsy-related variables on performance. This retrospective study involved a cohort of 54 adults who had been diagnosed with TLE and had undergone a neuropsychological assessment that included four memory tests traditionally used to measure either semantic memory (picture naming, animal fluency) or episodic memory (story recall, word list recall) at a single epilepsy surgery center in Australia. Principal component analysis revealed two factors albeit with unexpected loadings. Picture naming and story recall loaded on one factor. Animal fluency and word list recall loaded on another factor. There was no evidence of a double dissociation between semantic and episodic memory at an individual level. Left hemisphere seizure focus and early age of seizure onset related to worse performance on word list recall, picture naming and animal fluency, respectively. Our study highlights the importance of caution when interpreting the results of neuropsychological assessments, as not all putative tests of semantic and episodic memory may necessarily be measuring the same construct. Future directions for research are also considered. [ABSTRACT FROM AUTHOR]

Apathy is the commonest neuropsychiatric symptom in Alzheimer's disease (AD). Previous findings suggest that apathy is caused by a communication breakdown between functional neural networks involved in motivational–affective processing. This study investigated the relationship between white matter (WM) damage and apathy in AD. Sixty-one patients with apathy (AP-PT) and 61 without apathy (NA-PT) were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and matched for cognitive status, age and education. Sixty-one cognitively unimpaired (CU) participants were also included as controls. Data on cognitive performance, cerebrospinal fluid biomarkers, brain/WM hyperintensity volumes and diffusion tensor imaging indices were compared across groups. No neurocognitive differences were found between patient groups, but the AP-PT group had more severe neuropsychiatric symptoms. Compared with CU participants, only apathetic patients had deficits on the Clock Drawing Test. AP-PT had increased WM damage, both macrostructurally, i.e., larger WM hyperintensity volume, and microstructurally, i.e., increased radial/axial diffusivity and reduced fractional anisotropy in the fornix, cingulum, anterior thalamic radiations and superior longitudinal and uncinate fasciculi. AP-PT showed signs of extensive WM damage, especially in associative tracts in the frontal lobes, fornix and cingulum. Disruption in structural connectivity might affect crucial functional inter-network communication, resulting in motivational deficits and worse cognitive decline. [ABSTRACT FROM AUTHOR]

In today's world, Global Competence represents a fundamental disposition for teachers who must be able to teach effectively in classrooms with students from diverse backgrounds and manage multiple learning contexts. For these reasons, it is necessary to set up educational activities during initial teacher education programs aimed at developing and assessing preservice teachers' ability to be Global Competent. This study was aimed at designing and creating a set of rubrics that can be used by either teacher educators or preservice teachers, in this case, as a self-assessment instrument. The research design was based on a modified Delphi method composed of five rounds to collect both qualitative and quantitative data. A panel of 31 experts was involved in an iterative process until a consensus among the experts was reached. The rubrics can be employed in several contexts and situations such as: before and after an international experience, during or after a simulation or a workshop based on intercultural and real-world situations. [ABSTRACT FROM AUTHOR]

Environmental monitoring (EM) programs are designed to detect the presence of pathogens in food manufacturing environments, with the goal of preventing microbial contamination of food. Nevertheless, limited knowledge exists regarding the influence of environmental conditions on microbial recovery during EM. This study uses a commercially available polyurethane foam EM tool to determine the influence of environmental factors on the recovery of foodborne pathogens. The specific objectives of this study were to determine if environmental conditions and surface composition impact the recovery of sought-after microorganisms found in food processing environments. These data are compared across (i) microorganism type, (ii) surface type, (iii) environmental temperature and relative humidity (RH), and (iv) exposure time. Two bacteria (Listeria monocytogenes and Salmonella Typhimurium) and one human norovirus surrogate (Tulane virus) were inoculated onto three nonporous surfaces (polypropylene, stainless steel, and neoprene). Surfaces were held in an environmental chamber for 24 or 72 h at 30°C with 30% RH, 6°C with 85% RH, and 30°C with 85% RH. Data indicate that microbial recovery from environmental surfaces significantly (P ≤ 0.05) varies by microorganism type, environmental conditions, and exposure time. For instance, all microorganisms were significantly different from each other, with the greatest mean log reduction being Tulane virus and the lesser reduction being L. monocytogenes at 4.94 ± 1.75 log PFU per surface and 2.54 ± 0.91 log CFU per surface, respectively. Overall, these data can be used to improve the effectiveness of EM programs and underscores the need to better comprehend how EM test results are impacted by food manufacturing environmental conditions. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with knee osteoarthritis (OA). Weight loss, alongside exercise, is a recommended treatment for individuals with knee OA and overweight/obesity. However, many patients cannot access weight loss specialists such as dietitians. Innovative care models expanding roles of other clinicians may increase access to weight loss support for people with knee OA. Physiotherapists may be well placed to deliver such support. This two-group parallel, superiority randomized controlled trial aims to compare a physiotherapist-delivered diet and exercise program to an exercise program alone, over 6 months. The primary hypothesis is that the physiotherapist-delivered diet plus exercise program will lead to greater weight loss than the exercise program.Methods: 88 participants with painful knee OA and body mass index (BMI) > 27 kg/m2 will be recruited from the community. Following baseline assessment, participants will be randomised to either exercise alone or diet plus exercise groups. Participants in the exercise group will have 6 consultations (20-30 min) via videoconference with a physiotherapist over 6 months for a strengthening exercise program, physical activity plan and educational/exercise resources. Participants in the diet plus exercise group will have 6 consultations (50-75 min) via videoconference with a physiotherapist prescribing a ketogenic very low-calorie diet with meal replacements and educational resources to support weight loss and healthy eating, plus the intervention of the exercise only group. Outcomes are measured at baseline and 6 months. The primary outcome is percentage change in body weight measured by a blinded assessor. Secondary outcomes include self-reported knee pain, physical function, global change in knee problems, quality of life, physical activity levels, and internalised weight stigma, as well as BMI, waist circumference, waist-to-hip ratio, physical performance measures and quadriceps strength, measured by a blinded assessor. Additional measures include adherence, adverse events, fidelity and process measures.Discussion: This trial will determine whether a physiotherapist-delivered diet plus exercise program is more effective for weight loss than an exercise only program. Findings will inform the development and implementation of innovative health service models addressing weight management and exercise for patients with knee OA and overweight/obesity.Trial Registration: NIH US National Library of Medicine, Clinicaltrials.gov NCT04733053 (Feb 1 2021). [ABSTRACT FROM AUTHOR]

Kv1.3 is a voltage-gated K+-selective channel with roles in immunity, insulin-sensitivity, neuronal excitability and olfaction. Despite being one of the largest ionic conductances of the platelet surface membrane, its contribution to platelet function is poorly understood. Here we show that Kv1.3-deficient platelets display enhanced ADP-evoked platelet aggregation and secretion, and an increased surface expression of platelet integrin αIIb. In contrast, platelet adhesion and thrombus formation in vitro under arterial shear conditions on surfaces coated with collagen were reduced for samples from Kv1.3−/- compared to wild type mice. Use of collagen-mimetic peptides revealed a specific defect in the engagement with α2β1. Kv1.3−/- platelets developed significantly fewer, and shorter, filopodia than wild type platelets during adhesion to collagen fibrils. Kv1.3−/- mice displayed no significant difference in thrombus formation within cremaster muscle arterioles using a laser-induced injury model, thus other pro-thrombotic pathways compensate in vivo for the adhesion defect observed in vitro. This may include the increased platelet counts of Kv1.3−/- mice, due in part to a prolonged lifespan. The ability of Kv1.3 to modulate integrin-dependent platelet adhesion has important implications for understanding its contribution to normal physiological platelet function in addition to its reported roles in auto-immune diseases and thromboinflammatory models of stroke. [ABSTRACT FROM AUTHOR]

The article focuses on the Christian author James Dobson issued a grave warning about fantasy roleplaying games. It mentions that Dungeons & Dragons, a tabletop roleplaying game that starred elves, orcs, and other fantasy beings, had become synonymous with the "Satanic Panic" that had gripped the public imagination for the better part of a decade. It also mentions that game designer, Gary Gygax started a company, Tactical Studies Rules (TSR), to disseminate Dungeons & Dragons and tabletop roleplaying games like it.

In this essay, I story my discovery of breastmilk markets and my subsequent fieldwork and research program in the milk banking industry. I discuss how my experience growing up as the oldest of six children and daughter of a Labor and Delivery nurse foregrounded my curiosity and commitment to the organization of donor milk. I then use concrete research poetry to convey the political conditions that gave rise to this industry. In response, I reflect on the contrast between my childfree identity and the lived circumstances of milk donors/recipients by pondering the shared consequences of pronatalist and disciplinary discourses. Finally, I note the importance of community knowledge of milk banking (regardless of parental status) and offer questions to inspire further research in health communication. [ABSTRACT FROM AUTHOR]

The article focuses on teaching the history of sexuality and approach has been shaped in part by sex education initiatives like the Sex and History project at the University of Exeter. It mentions sources that some might see same-sex the first time, they might end up discussing subjects that feel sensitive or embarrassing with their peers. It also mentions pornographic image, produced in the imperial context, that depicts the bodies of colonized peoples and perpetuating racist stereotypes.

Purpose: To evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of single and multiple doses of PF-06881894 (pegfilgrastim-apgf; Nyvepria™), a biosimilar to reference pegfilgrastim (Neulasta®), in women with non-distantly metastatic breast cancer.Methods: In Phase I (Cycle 0) of this Phase I/II study, the PD response (absolute neutrophil count [ANC]; CD34 + count), PK profile, and safety of a single 3- or 6-mg subcutaneous dose of PF-06881894 were assessed in chemotherapy-naïve patients before definitive breast surgery. In Phase II (Cycles 1-4), the PD response (duration of severe neutropenia [DSN, Cycle 1], ANC [Cycles 1 and 4]) and PK profile (Cycles 1 and 4) of single and multiple 6-mg doses of PF-06881894 concomitant with chemotherapy and after definitive breast surgery were assessed.Results: Twenty-five patients (mean age 59 years) were enrolled (Cycle 0, n = 12; Cycles 1-4, n = 13). In Cycle 0, PD responses and PK values were lower with 3-mg versus 6-mg PF-06881894. In Cycles 1 and 4, mean DSN was 0.667 days after single or multiple 6-mg doses of PF-06881894, respectively. In Cycle 4 versus Cycle 1, PD responses were more robust; PK values (mean area under the curve, maximum concentration) were lower; and clearance values were higher. The safety profile of PF-06881894 was similar to that for reference pegfilgrastim.Conclusion: PF-06881894 as a single 3- or 6-mg dose prior to definitive surgery, or multiple 6-mg/cycle doses postoperatively, with/without myelosuppressive chemotherapy, was consistent with the clinical pharmacology and safety profile of reference pegfilgrastim.Trial Registration: October 2017. ClinicalTrials.gov Identifier: NCT02650193. EudraCT Number: 2015-002057-35. [ABSTRACT FROM AUTHOR]

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers. The working group additionally invited genetic and clinical experts from the USA, India, Japan, Australia, South‐Africa, and Brazil to provide a global perspective. Six virtual meetings were organized to reach consensus on the minimal requirements for genetic confirmation of FSHD1 and FSHD2. Here, we present the clinical and genetic features of FSHD, specific features of FSHD1 and FSHD2, pros and cons of established and new technologies (Southern blot in combination with either linear or pulsed‐field gel electrophoresis, molecular combing, optical genome mapping, FSHD2 methylation analysis and FSHD2 genotyping), the possibilities and challenges of prenatal testing, including pre‐implantation genetic testing, and the minimal requirements and recommendations for genetic confirmation of FSHD1 and FSHD2. This consensus is expected to contribute to current clinical management and trial‐readiness for FSHD. [ABSTRACT FROM AUTHOR]

The article evaluates the online-learning platform, MasterClass, founded and launched by David Rogier, and discusses the company's model, the price of its subscription, and its White House series.

Adult referrals to specialist autism spectrum disorder diagnostic services have increased in recent years, placing strain on existing services. It was proposed that the Ritvo Autism Asperger's Diagnostic Scale could be used as a screening tool, in order to identify and prioritise patients most likely to receive an ASD diagnosis. This study evaluates the validity of the RAADS-R as a screening tool for ASD in an adult population. Retrospective case note analysis was used to evaluate the efficacy of the RAADS-R as a screening tool to predict ASD diagnostic outcomes in 50 service users of a NHS specialist autism service. Results indicate no association between RAADS-R scores and clinical diagnostic outcome, suggesting the RAADS-R is not an effective screening tool for identifying service users most likely to receive an ASD diagnosis. In conclusion, used as a self-report measure pre-full diagnostic assessment, the RAADS-R lacks predictive validity and is not a suitable screening tool for adults awaiting autism assessments. Future research should aim to identify reliable screening tools for this purpose. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Netflix production asking couples for choosing between two markers of adulthood such as legal union or property ownership.

Introduction and hypothesis: Numerous analytic observational studies assess family history as a risk factor for POP and report a wide range of associations. This review aims to systematically evaluate the role of family history of POP in relation to POP risk and its recurrence. Methods: A review was performed of the PubMed/MEDLINE database with search criteria specifying family history, risk factors, POP, and their synonyms as title/abstract keywords, as well as MESH terms, up to March 2020. We aggregated evidence across studies with fixed effects (FE) and random effects (RE) meta-analysis. Results: Forty-three articles underwent full-text review. Eighteen independent studies evaluating the relationship between family history of POP and POP risk in 3639 POP cases and 10,912 controls were eligible for meta-analysis. Four studies evaluating family history and POP recurrence in 224 recurrent cases and 400 non-recurrent cases were eligible for inclusion into another meta-analyses. A positive family history of POP is on average associated with 2.3- to 2.7-fold increased risk for POP (RE OR = 2.64; 95% CI = 2.07, 3.35) as well as a 1.4-fold increased risk for POP recurrence (FE OR = 1.44; 95% CI = 1.00, 2.08). Meta-analysis estimates of POP risk varied by study design, definition of family history, and model adjustment status. We found evidence that publication bias and recall bias are a possibility. Conclusions: Family history of POP is a risk factor for both POP presence and recurrence. However, reported magnitudes may be overestimates due to confounding, recall bias, and publication bias. [ABSTRACT FROM AUTHOR]

Advances in digital health have enabled clinicians to move away from a reliance on face to face consultation methods towards making use of modern video and web-based conferencing technology. In the context of the COVID-19 pandemic, remote telecommunication methods have become much more common place in mental health settings. The current study sought to investigate whether remote telecommunication methods are preferable to face to face consultations for adults referred to an Autism and ADHD Service during the COVID-19 pandemic. Also, whether there are any differences in preferred consultation methods between adults who were referred for an assessment of Autism as opposed to ADHD. 117 service users who undertook assessment by the ADHD and Autism Service at South West Yorkshire NHS Partnership Foundation Trust from April to September 2020 completed an adapted version of the Telehealth Usability Questionnaire (TUQ). Results demonstrated that service users found remote telecommunication to be useful, effective, reliable and satisfactory. Despite this, almost half of service users stated a general preference for face to face consultations. There was no difference in the choice of methods of contact between Autism and ADHD pathways. Remote telecommunication methods were found to be an acceptable medium of contact for adults who undertook an assessment of Autism and ADHD at an NHS Service during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The development of the SARS-CoV-2 pandemic has prompted an extensive worldwide sequencing effort to characterise the geographical spread and molecular evolution of the virus. A point mutation in the spike protein, D614G, emerged as the virus spread from Asia into Europe and the USA, and has rapidly become the dominant form worldwide. Here we review how the D614G variant was identified and discuss recent evidence about the effect of the mutation on the characteristics of the virus, clinical outcome of infection and host immune response. [ABSTRACT FROM AUTHOR]

Background: The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) module four assessment for diagnosing autism spectrum disorder in adults has shown good sensitivity and specificity in research settings. Method: This study aimed to evaluate the predictive accuracy of the ADOS-2 module four by investigating the components of the assessment, in relation to diagnostic outcome in a clinical setting. Data from 88 service users referred to a Specialist Adult Autism Service was explored. Results: ADOS-2 scores failed to predict the diagnostic outcome (overall sensitivity = 92%, specificity = 57%). Interestingly, scores from the 'restricted interests' component of the ADOS-2 have the potential to predict diagnostic outcome, despite this domain not been included in the scoring algorithm. Conclusions: Based on our findings, we recommend clinicians are cautious when interpreting results of the ADOS-2 assessment. [ABSTRACT FROM AUTHOR]

In this issue, Schroder I et al. i assess the impacts of mechanical strain and salt on macrophage inflammatory responses I in vitro i . Schröder et al.1 show that both tensile and compressive strain increase TNF and IL-6 production from macrophages, whereas only compression increases levels of secreted PGE2. Broadly, NFAT5 appears to positively regulate TNF and PGE SB 2 sb production in macrophages, whereas it suppresses IL-6 expression. Intriguingly, gene silencing studies suggested a role for NFAT5 in pressure-induced IL-6 production, whereas it inhibited basal IL-6 expression and contributed to the repressive effect of salt on pressure-induced IL-6 production. [Extracted from the article]

As pharmacokinetic modifiers, cell penetrating peptides (CPPs) have proven utility for the delivery of otherwise impermeable cargoes into the discrete intracellular compartments of eukaryotic cells. Methods for the molecular optimisation of CPP sequences can significantly increase the performance of novel vectors matched to a specific delivery function. Moreover, the 'information rich' composition and inherent molecular flexibility of many CPPs can also facilitate their interaction with intracellular proteins and other cellular structures. This proteomimetic property of CPPs has been exploited in the design of bioportides, bioactive CPPs that regulate cellular functions often by binding relatively flat PPI interfaces to achieve a dominant negative action. This new biology of CPPs is rapidly gathering momentum through the design and synthesis of a bewildering variety of peptides that may be, in whole or part, linear, helical, cyclic and/or chimeric in nature. A particular emphasis of contemporary CPP‐centred drug discovery is the unmet medical need of cancer, though the biomedical scope of bioportide applications is impressively broad including cellular signalling and reprogramming. We are hopeful that one or more of the fascinating studies described herein will translate into the clinic to establish bioportide technologies as a viable option for drug discovery. [ABSTRACT FROM AUTHOR]

Plant stress phenotyping is essential to select stress-resistant varieties and develop better stress-management strategies. Standardization of visual assessments and deployment of imaging techniques have improved the accuracy and reliability of stress assessment in comparison with unaided visual measurement. The growing capabilities of machine learning (ML) methods in conjunction with image-based phenotyping can extract new insights from curated, annotated, and high-dimensional datasets across varied crops and stresses. We propose an overarching strategy for utilizing ML techniques that methodically enables the application of plant stress phenotyping at multiple scales across different types of stresses, program goals, and environments. Plant stress phenotyping is challenging to implement at multiple organizational scales (leaf, canopy, field). There is a need to improve the speed, accuracy, reliability, and scalability of stress phenotyping while allowing flexibility for highly variable program goals. Advances in ML algorithms create opportunities for augmented plant stress phenotyping to address these challenges. [ABSTRACT FROM AUTHOR]

A theoretical study of the a semiconducting carbon nanotube (CNT) bonding to an aluminum electrode is presented using density functional theory to determine the electronic structure, and charge transport across the junction is studied using non-equilibrium Green's functions. The properties of CNT-metal junctions are of interest for optimizing metal-semiconductor junctions for Schottky barrier transistors and for the formation of Ohmic contacts for nanoelectronics. We first consider the properties of an undoped (16,0) CNT bonded to an aluminum electrode, including an analysis of metal induced gap states and examination of the surface dipole. The junction is then modified by introduction of substitutional dopants into the CNT using nitrogen and boron to form n- and p-type semiconductors, respectively, and the resulting impact of the doping on current transport across the junctions is calculated. As an alternative doping strategy, tetrathiafulvalene is introduced endohedrally and found to act as an n-type dopant in agreement with previous experimental studies. From electron transmission and current voltage characteristics, it is found that the doped junctions can be engineered to have much lower onset resistances relative to the undoped junction. It is found that the current-voltage characteristics display increased resistance for larger forward and reverse biases: For one polarity, the resistance increase is associated with the introduction of the CNT band gap into the voltage bias window, whereas for the opposing voltage polarity, the resistance increase is due to large charge carrier-substitutional dopant scattering. For the case of the endohedral doping scheme, it is found that the carrier-dopant scattering is effectively absent. [ABSTRACT FROM AUTHOR]