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Self-harm is among the top five causes of acute hospital admissions and ambulance clinicians are often the first point of contact. However, the Emergency Department (ED) may not be the most appropriate place of care and little is known about the existence or nature of alternative pathways available to UK ambulance services. This survey describes the current management pathways used by ambulance services for patients who have self-harmed.

A structured questionnaire was sent to all UK ambulance services by email and followed up by telephone in 2018. Three independent researchers (two clinical) coded responses which were analysed thematically.

All 13 UK ambulance services responded to the survey nine by email and four by telephone interview. Two services reported a service-wide protocol for managing people presenting with self-harm, with referral to mental health crisis team available as an alternative to conveyance to ED, following on-scene psychosocial assessment. Four services reported local pathways for managing mental health patients which included care of patients who had self-harmed. Four services reported being in the process of developing pathways for managing mental health patients. Six services reported no service-wide nor local pathways for managing self-harm patients. No robust evaluation of new care models was reported.

Practice in ambulance services in the UK is variable, with a minority having a specific clinical pathway for managing self-harm, with an option to avoid ED. New pathways for patients who have self-harmed must be evaluated in terms of safety, clinical and cost-effectiveness.
Practice in ambulance services in the UK is variable, with a minority having a specific clinical pathway for managing self-harm, with an option to avoid ED. New pathways for patients who have self-harmed must be evaluated in terms of safety, clinical and cost-effectiveness.
Oropharyngeal squamous cell carcinoma is the most common human papillomavirus (HPV)-associated cancer in the UK, but little is known about the prevalence of oropharyngeal HPV in sexually active teenagers. We investigated reported HPV vaccination coverage (in females) and prevalence of oropharyngeal HPV in sexually active students attending six technical colleges in London, UK.

In 2017, we obtained mouthwash samples and questionnaires from male and female students taking part in the 'Test n Treat' chlamydia screening trial. Samples were subjected to HPV genotyping.

Of 232 participants approached, 202 (87%) provided a mouthwash sample and questionnaire. Participants' median age was 17 years and 47% were male. Most (73%) were from black and minority ethnic groups, 64% gave a history of oral sex, 52% reported having a new sexual partner in the past 6 months, 33% smoked cigarettes, 5.9% had concurrent genitourinary
infection and 1.5%
and 5.0% were gay or bisexual. Only 47% (50/107) of females reported being vaccinated against HPV 16/18, of whom 74% had received ≥2 injections. HPV genotyping showed three mouthwash samples (1.5%, 95% CI 0.3% to 4.3%) were positive for possible high-risk human papillomavirus (HR-HPV), one (0.5%, 0.0% to 2.7%) for low-risk HPV 6/11, but none (0.0%, 0.0% to 1.8%) for HR-HPV. Adavosertib in vivo Four samples (2.0%, 0.5% to 5.0%) were positive for HPV16 using a HPV16 type-specific quantitative PCR, but these were at a very low copy number and considered essentially negative.

Despite the high prevalence of oral sex and genitourinary chlamydia and low prevalence of HPV vaccination, the prevalence of oropharyngeal HR-HPV in these adolescents was negligible.
Despite the high prevalence of oral sex and genitourinary chlamydia and low prevalence of HPV vaccination, the prevalence of oropharyngeal HR-HPV in these adolescents was negligible.We present Nubeam (nucleotide be amatrix) as a novel reference-free approach to analyze short sequencing reads. Nubeam represents nucleotides by matrices, transforms a read into a product of matrices, and assigns numbers to reads based on the product matrix. Nubeam capitalizes on the noncommutative property of matrix multiplication, such that different reads are assigned different numbers and similar reads similar numbers. A sample, which is a collection of reads, becomes a collection of numbers that form an empirical distribution. We demonstrate that the genetic difference between samples can be quantified by the distance between empirical distributions. Nubeam includes the k-mer method as a special case, but unlike the k-mer method, it is convenient for Nubeam to account for GC bias and nucleotide quality. As a reference-free approach, Nubeam avoids reference bias and mapping bias, and can work with organisms without reference genomes. Thus, Nubeam is ideal to analyze data sets from metagenomics whole genome shotgun (WGS) sequencing, where the amount of unmapped reads is substantial. When applied to a WGS sequencing data set to quantify distances between metagenomics samples from various human body habitats, Nubeam recapitulates findings made by mapping-based methods and sheds light on contributions of unmapped reads. Nubeam is also useful in analyzing 16S rRNA sequencing data, which is a more prevalent type of data set in metagenomics studies. In our analysis, Nubeam recapitulated the findings that natural microbiota in mouse gut are resilient under challenges, and Nubeam detected differences in vaginal microbiota between cases of polycystic ovary syndrome and healthy controls.The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of nasopharyngeal swabs (NPS) and viral transport media, necessitating the search for alternate diagnostic specimens, such as saliva. We directly compared matched saliva and NPS specimens from symptomatic patients suspected of having COVID-19. An enhanced saliva specimen (i.e., strong sniff, elicited cough, and collection of saliva/secretions) was collected without transport medium prior to collection of NPS from 224 patients with symptoms deemed consistent with COVID-19. Both specimens were tested with the CDC 2019 nCoV real-time RT-PCR diagnostic panel (4 February 2020 version), with the NPS result used as the reference standard. For the 216 patients included in the final analysis, there was 100% positive agreement (38/38 positive specimens) and 99.4% negative agreement (177/178 negative specimens). The one discrepant specimen had the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed in the saliva specimen using an alternate FDA EUA assay. The overall mean difference in cycle threshold (CT ) values for the positive NPS and saliva specimens was -3.61 (95% confidence interval [CI], -5.78 to -1.44; P = 0.002). An enhanced saliva specimen performed as well as NPS for the qualitative detection of SARS-CoV-2 in symptomatic patients, although the overall mean viral load in saliva was lower.
GEP-NENs are rare malignancies with increasing incidence. Their molecular characteristics are still undefined. We explored the underlying biology of GEP-NENs and the differences between gastrointestinal (GI) and pancreatic (PNEN), high-grade (HG), and low-grade (LG) tumors.

GEP-NENs were analyzed using next-generation sequencing (NGS; MiSeq on 47 genes, NextSeq on 592 genes), IHC, and
hybridization. Tumor mutational burden (TMB) was calculated on the basis of somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci.

In total, 724 GEP-NENs were examined GI (
= 469), PNEN (
= 255), HG (
= 135), and LG (
= 335). Forty-nine percent were female, and median age was 59. Among LG tumors, the most frequently mutated genes were
(13%),
(10%), and
(10%). HG tumors showed
(51%),
(30%),
(27%), and
(23%). Immune-related biomarkers yielded a lower prevalence in LG tumors compared with HG [MSI-H 0% vs. 4% (
= 0.04), PD-L1 overexpression 1% vs. 6% (
= 0.03), TMB-high 1% vs. 7% (
= 0.05)]. Compared with LG, HG NENs showed a higher mutation rate in
(5.4% vs. 0%,
< 0.0001),
(29.4% vs. 2.6%,
< 0.0001), and
(7% vs. 0.3%,
< 0.0001). When compared with GI, PNEN carried higher frequency of
(25.9% vs. 0.0%,
< 0.0001),
(8.6% vs. 0.8%,
= 0.005),
(20.6% vs. 2.0%,
= 0.007), and
(6.3% vs. 0.0%,
= 0.007), but lower frequency of mutations in
(1.0% vs. 13.8%,
< 0.0001).

Significant molecular differences were observed in GEP-NENs by tumor location and grade, indicating differences in carcinogenic pathways and biology.
Significant molecular differences were observed in GEP-NENs by tumor location and grade, indicating differences in carcinogenic pathways and biology.Isocitrate dehydrogenase (IDH) active-site mutations cause a neomorphic enzyme activity that results in the formation of supraphysiologic concentrations of D-2-hydroxyglutarate (D-2HG). D-2HG is thought to be an oncometabolite that drives the formation of cancers in a variety of tissue types by altering the epigenetic state of progenitor cells by inhibiting enzymes involved in histone and DNA demethylation. This model has led to the development of pharmacologic inhibitors of mutant IDH activity for anticancer therapy, which are now being tested in several clinical trials. Emerging evidence in preclinical glioma models suggests that the epigenetic changes induced by D-2HG may persist even after mutant IDH activity is inhibited and D-2HG has returned to basal levels. Therefore, these results have raised questions as to whether the exploitation of downstream synthetic lethal vulnerabilities, rather than direct inhibition of mutant IDH1, will prove to be a superior therapeutic strategy. In this review, we summarize the preclinical evidence in gliomas and other models on the induction and persistence of D-2HG-induced hypermethylation of DNA and histones, and we examine emerging lines of evidence related to altered DNA repair mechanisms in mutant IDH tumors and their potential for therapeutic exploitation.
Major ECG abnormalities have been associated with increased risk of cardiovascular disease (CVD) burden in asymptomatic populations. However, sex differences in occurrence of major ECG abnormalities have been poorly studied, particularly across ethnic groups. The objectives were to investigate (1) sex differences in the prevalence of major and, as a secondary outcome, minor ECG abnormalities, (2) whether patterns of sex differences varied across ethnic groups, by age and (3) to what extent conventional cardiovascular risk factors contributed to observed sex differences.

Cross-sectional analysis of population-based study.

Multi-ethnic, population-based Healthy Life in an Urban Setting cohort, Amsterdam, the Netherlands.

8089 men and 11 369 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 18-70 years without CVD.

Age-adjusted and multivariable logistic regression analyses were performed to study sex differences in prevalence of major and, as secondthan men. However, sex differences were less apparent in ethnic minority groups. Conventional risk factors did not contribute substantially to observed sex differences.
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