PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations.

Aims: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.

Methods And Results: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)].

"They're scared that somebody's gonna judge them": Female African American youth in foster care's perspectives on sexual and reproductive health communication with caregivers.

Background: Obtaining accurate information is critical for youth's sexual and reproductive health (SRH). Youth not in foster care often learn about SRH from their biological parents. Separated from their biological parents, youth in care depend on healthcare providers and caregivers for SRH information.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.

"If the social circle is engaged, more pregnant women will successfully quit smoking": a qualitative study of the experiences of midwives in the Netherlands with smoking cessation care.

Background: If smoking is common within a pregnant woman's social circle, she is more likely to smoke and her chances of succeeding in quitting smoking are reduced. It is therefore important to encourage smoking cessation in a pregnant woman's social circle. Midwives are ideally positioned to help pregnant women and members of their social circle quit smoking but there is currently little knowledge about if and how midwives approach smoking cessation with pregnant women's social circles.

Candidate Tidal Disruption Event AT2019fdr Coincident with a High-Energy Neutrino.

The origins of the high-energy cosmic neutrino flux remain largely unknown. Recently, one high-energy neutrino was associated with a tidal disruption event (TDE). Here we present AT2019fdr, an exceptionally luminous TDE candidate, coincident with another high-energy neutrino.

Association of Task-Shared Psychological Interventions With Depression Outcomes in Low- and Middle-Income Countries: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Task sharing, the training of nonspecialist workers with no formal experience in counseling, is a promising strategy for addressing the large gap in treatment for depression in low- and middle-income countries (LMICs).

Objective: To examine the outcomes and moderators of task-shared psychological interventions associated with depression severity, response, and remission.

Data Sources: Systematic literature searches in PubMed, Embase, PsycINFO, and Cochrane Library up to January 1, 2021.

DEPEND study protocol: early detection of patients with pancreatic cancer - a pilot study to evaluate the utility of faecal elastase-1 and C-mixed triglyceride breath test as screening tools in high-risk individuals.

Introduction: Pancreatic cancer (PC) is the fifth leading cause of cancer-related death in the UK. The incidence of PC is increasing, with little or no improvement in overall survival and the best chance for long-term survival in patients with PC relies on early detection and surgical resection. In this study, we propose the use of a diagnostic algorithm that combines tests of pancreatic exocrine function (faecal elastase-1 (FE-1) test and the C-mixed triglyceride (C-MTG) breath test) to identify patients with PC that urgently needs imaging studies.

Endometrial scratch to increase live birth rates in women undergoing first-time in vitro fertilisation: RCT and systematic review.

Background: In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation 'add-on' that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use.

Objectives: (1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the 'Endometrial Scratch Trial') and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle.

A novel blinding protocol to test participant and therapist blinding during dry needling: a randomised controlled experiment.

Objectives: Dry needling is widely used in physiotherapy. Lack of blinding in clinical trials means that dry needling effects and mechanisms remain unclear, with blinding issues accepted as an unavoidable barrier to better evidence. The authors aimed to overcome this barrier by designing a protocol to double-blind dry needling trials.

A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI.

Study Question: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment?

Summary Answer: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI).

What Is Known Already: ES is an 'add-on' treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use.

Study Design, Size, Duration: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019.

Blinding Strategies in Dry Needling Trials: Systematic Review and Meta-Analysis.

Background: Blinding of participants and therapists in trials of physical interventions is a significant and ongoing challenge. There is no widely accepted sham protocol for dry needling.

Purpose: The purpose of this review was to summarize the effectiveness and limitations of blinding strategies and types of shams that have been used in dry needling trials.

Hospital Attendances and Acute Admissions Preceding a Diagnosis of Occupational Asthma.

Purpose: Occupational exposures are a common cause of adult-onset asthma; rapid removal from exposure to the causative agent offers the best chance of a good outcome. Despite this, occupational asthma (OA) is widely underdiagnosed. We aimed to see whether chances of diagnosis were missed during acute hospital attendances in the period between symptom onset and the diagnosis of OA.

What happens to agreement over time? A longitudinal study of self-reported substance use compared to saliva toxicological testing among subsidized housing residents.

The agreement between self-reported and toxicologically verified substance use provides important information about the validity of self-reported use. While some studies report aggregate agreement across follow-up points, only a few have examined the agreement at each time point separately. An overall rate of agreement across time may miss changes that occur as people progress through a research study.

Interlaboratory Comparison of Hydrogen-Deuterium Exchange Mass Spectrometry Measurements of the Fab Fragment of NISTmAb.

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) is an established, powerful tool for investigating protein-ligand interactions, protein folding, and protein dynamics. However, HDX-MS is still an emergent tool for quality control of biopharmaceuticals and for establishing dynamic similarity between a biosimilar and an innovator therapeutic. Because industry will conduct quality control and similarity measurements over a product lifetime and in multiple locations, an understanding of HDX-MS reproducibility is critical.

Multigenerational obesity-induced perturbations in oocyte-secreted factor signalling can be ameliorated by exercise and nicotinamide mononucleotide.

Study Question: Can maternal and offspring high-fat diet (HFD)-induced changes in mRNA expression levels in mice be ameliorated by interventions in female offspring?

Summary Answer: Our results indicate that exercise and nicotinamide mononucleotide (NMN) can ameliorate the negative effects of maternal and post-weaning HFD in female offspring.

What Is Known Already: Maternal and post-weaning HFD can perturb offspring developmental trajectories. As rates of maternal obesity are rising globally, there is a need for effective treatments in offspring to ameliorate the negative effects from a maternal obesogenic environment.

Intensified Infliximab Induction is Associated with Improved Response and Decreased Colectomy in Steroid-Refractory Paediatric Ulcerative Colitis.

Background: Infliximab pharmacokinetics in steroid-refractory [SR] ulcerative colitis [UC] suggest a need for higher dosing, but data concerning efficacy of intensification in this setting are lacking in children and inconsistent overall.

Methods: Paediatric patients [N = 125] treated with infliximab for SR or steroid-dependent UC were retrospectively reviewed. Outcomes [clinical response and remission, colectomy, mucosal healing, safety] with standard vs intensified induction [mean induction dose ≥7 mg/kg or interval ≤5 weeks between doses 1 and 3] were compared.

Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances.

Tumour-specific, immuno-based therapeutic interventions can be considered as safe and effective approaches for cancer therapy. Exploitation of nano-vaccinology to intensify the cancer vaccine potency may overcome the need for administration of high vaccine doses or additional adjuvants and therefore could be a more efficient approach. Carbon nanotube (CNT) can be described as carbon sheet(s) rolled up into a cylinder that is nanometers wide and nanometers to micrometers long.

Probing human sperm metabolism using 13C-magnetic resonance spectroscopy.

Study Question: Can 13C-Magnetic Resonance Spectroscopy (MRS) of selected metabolites provide useful information about human sperm metabolism and how glycolysis or oxidative phosphorylation are used by different sperm populations?

Summary Answer: Sperm populations, prepared by density gradient centrifugation (DGC) and incubated with either 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate, showed consistent evidence of metabolism generating principally lactate and more intermittently bicarbonate, and significantly more lactate was produced from 13Cu-glucose by vital or motile sperm recovered from the 40/80% interface compared to those from the pellet, which could not be accounted for by differences in the non-sperm cells present.

What Is Known Already: Previous studies have focused on CO2 or other specific metabolite production by human sperm and there remains considerable debate about whether glycolysis and/or oxidative phosphorylation is the more important pathway for ATP production in sperm.

Study Design, Size, Duration: Sperm populations were prepared by DGC and subjected to 13C-MRS to answer the following questions.

Patient Beliefs and Preferences Regarding Surrogate Decision Makers.

Objectives: Many patients lose the capacity to make medical decisions because of severe illness or the effects of sedation or anesthesia. Most states in the United States designate the next of kin (NOK) as a default surrogate decision maker (SDM), but this may not always reflect patient preferences. Our objective was to determine how frequently the default SDM matched the patient's preferred SDM, and whether patients knew who would serve as their SDM should they become incapacitated.

Resistance to peer influence and crime desistance in emerging adulthood: A moderated mediation analysis.

The current study sought to determine whether resistance to peer pressure contributes to crime desistance by inhibiting proactive criminal thinking (moral disengagement), a social-cognitive variable that has been found to mediate the peer influence effect. Using data from the Pathways to Desistance study ( = 1,354), resistance to peer influence and peer delinquency were tested as predictors of subsequent offending when participants were 18, 19, and 20 years of age. Whereas peer delinquency (PD) facilitated future offending by increasing moral disengagement (MD), peer resistance inhibited future offending by decreasing moral disengagement.

Induced endometrial trauma (endometrial scratch) in the mid-luteal menstrual cycle phase preceding first cycle IVF/ICSI versus usual IVF/ICSI therapy: study protocol for a randomised controlled trial.

Introduction: Endometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth.

Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis.

Background: Insomnia is frequently comorbid with chronic migraine, and small trials suggest that cognitive-behavioral treatment of insomnia (CBTi) may reduce migraine frequency. This study endeavored to provide a quantitative synthesis of existing CBTi trials for adults with chronic migraine using Bayesian statistical methods, given their utility in combining prior knowledge with sequentially gathered data.

Methods: Completer analyses of 2 randomized trials comparing CBTi to a sham control intervention (Calhoun and Ford, 2007; Smitherman et al, 2016) were used to quantify the effects of a brief course of treatment on headache frequency.

Gaining an advantage by sitting an OSCE after your peers: A retrospective study.

To investigate if final year medical students undertaking an OSCE station at a later stage during examination diet were advantaged over their peers who undertook the same station at an earlier stage, and whether any such effect varies by the student's relative academic standing. OSCE data from six consecutive final year cohorts totaling 1505 students was analyzed. Mixed effects logistic regression was used to model factors associated with the probability of passing each individual station (random effects for students and circuits; and fixed effects to assess the association with day of examination, time of day, gender and year).

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion.

Background: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone.