Risk factors associated with knife-crime in United Kingdom among young people aged 10-24 years: a systematic review.

BACKGROUND: Since 2013, the number of violent crimes and offences by sharp instruments have increased continually, following a previous decrease, with majority of cases occurring among young people and in London. There is limited understanding surrounding the drivers influencing this change in trends, with mostly American-based research identifying risk factors. METHODS: The aim of this review is to identify and synthesise evidence from a range of literature to identify risk factors associated with weapon-related crime, for young people (aged 10-24 years) within the UK. A search strategy was generated to conduct a systematic search of published and grey literature within four databases (EMBASE, Medline, PsycINFO, and OpenGrey), identifying papers within a UK-context. Abstracts and full texts were screened by two independent reviewers to assess eligibility for inclusion, namely study focus in line with the objectives of the review. Weight of Evidence approach was utilised to assess paper quality, resulting in inclusion of 16 papers. Thematic analysis was conducted for studies to identity and categorise risk factors according to the WHO ecological model. RESULTS: No association was found between gender or ethnicity and youth violence, contrasting current understanding shown within media. Multiple research papers identified adverse childhood experiences and poor mental health as positively associated with youth and gang violence. It was suggested that community and societal risk factors, such as discrimination and economic inequality, were frequently linked to youth violence. A small number of studies were included within the review as this is a growing field of research, which may have led to a constrained number of risk factors identified. Due to heterogeneity of studies, a meta-analysis could not be conducted. As many studies displayed positive results, publication bias may be present. CONCLUSIONS: Several risk factors were identified, with evidence currently heterogeneous with minimal high-quality studies. However, findings highlight key areas for future research, including the link between poor mental health and knife-crime, and the trajectory into gangs. Risk factors should help identify high-risk individuals, targeting them within mitigation strategies to prevent involvement within crime. This should contribute to efforts aimed at reducing the rising crime rates within UK. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019138545 . Registered at PROSPSERO: 16/08/2019.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

This corrects the article DOI: 10.1038/bjc.2017.429.

Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy. In order to identify underlying genetic alterations and molecular mechanisms, we examined three family members affected by multinodular DNETs as well as 100 sporadic tumors from 96 patients, which had been referred to us as DNETs. We performed whole-exome sequencing on 46 tumors and targeted sequencing for hotspot FGFR1 mutations and BRAF p.V600E was used on the remaining samples. FISH, copy number variation assays and Sanger sequencing were used to validate the findings. By whole-exome sequencing of the familial cases, we identified a novel germline FGFR1 mutation, p.R661P. Somatic activating FGFR1 mutations (p.N546K or p.K656E) were observed in the tumor samples and further evidence for functional relevance was obtained by in silico modeling. The FGFR1 p.K656E mutation was confirmed to be in cis with the germline p.R661P variant. In 43 sporadic cases, in which the diagnosis of DNET could be confirmed on central blinded neuropathology review, FGFR1 alterations were also frequent and mainly comprised intragenic tyrosine kinase FGFR1 duplication and multiple mutants in cis (25/43; 58.1 %) while BRAF p.V600E alterations were absent (0/43). In contrast, in 53 cases, in which the diagnosis of DNET was not confirmed, FGFR1 alterations were less common (10/53; 19 %; p < 0.0001) and hotspot BRAF p.V600E (12/53; 22.6 %) (p < 0.001) prevailed. We observed overexpression of phospho-ERK in FGFR1 p.R661P and p.N546K mutant expressing HEK293 cells as well as FGFR1 mutated tumor samples, supporting enhanced MAP kinase pathway activation under these conditions. In conclusion, constitutional and somatic FGFR1 alterations and MAP kinase pathway activation are key events in the pathogenesis of DNET. These findings point the way towards existing targeted therapies.

The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type.

OBJECTIVE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome. METHODS: In 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank tests were performed on 257 cases with available survival data. RESULTS: The strongest prognostic factors were stage at diagnosis (p=2.72e-15) and treatment modality (p=3.87e-13). For FIGO stages II-IV, 5-year survival was 71% for patients who received HDC-aSCR, compared to 25% in patients who received conventional chemotherapy alone following surgery (p=0.002). Patients aged ≥40 had a worse outcome than younger patients (p=0.04). Twenty-six of 60 tested patients carried a germline SMARCA4 mutation, including all patients diagnosed <15years; carriers presented at a younger age than non-carriers (p=0.02). CONCLUSIONS: Stage at diagnosis is the most significant prognostic factor in SCCOHT and consolidation with HDC-aSCR may provide the best opportunity for long-term survival. The large fraction of SMARCA4 germline mutations carriers warrants genetic counseling for all patients.

Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

Differences in birthweight curves between newborns of immigrant mothers vs. infants born in their corresponding native countries: systematic overview.

BACKGROUND: Newborn weight may vary between ethnic groups, but it is not known if birthweight differences exist between term babies born to immigrant mothers compared with those born in their corresponding native countries. METHODS: We completed a systematic review of all birthweight curves published between 1980 and 2012, based on at least 100 singleton deliveries. We compared the 10th, 50th and 90th percentile birthweight values at 40 weeks gestation for male and female infants born in their native country vs. those infants born to mothers who had emigrated from their native country to Ontario, Canada. For the 50th percentile values, we also calculated a standardised pooled weighted difference and 95% confidence interval [CI] for both sexes. We also assessed whether birthweight differed over time, or if the differences varied by the Human Development Index (HDI) value for the native country. RESULTS: A total of 31 studies from 21 different countries met the inclusion criteria, comprising 13 317 578 males and 12 859 119 females born at 40 weeks gestation. There was a small non-significant rise in reported birthweight percentile values between 1983 and 2006. Nearly all infants born to women in their native country had lower birthweights than those born to mothers who had emigrated from the same country to Canada at the 10th, 50th and 90th percentiles. Overall, the 50th percentile weights differed by 115 g [95% CI 74, 156] for males and 122 g [95% CI 95, 150] for females. As HDI or median birthweight increased, birthweight differences were less pronounced, but not significantly so. CONCLUSIONS: Term birthweight percentiles are typically higher among term infants born to mother who immigrate to Canada than those of infants born in their respective native country.

Observational study of the association between diverse licensed premises types and alcohol-related violence in an inner-London borough.

BACKGROUND: An ecological correlation has been observed between licensed premises and alcohol-related violence (ARV). In the UK to date, no evidence directly connects alcohol-related harm to a single premises type. Recent policies have called for a diversified alcohol offer, yet quantitative evidence in support remains sparse. This study aims to inform policy by determining whether diversification of the alcohol economy is desirable and to inform the licensing process and submission of public health evidence. METHODS: Using 11 years of local licensing data from the London Borough of Southwark, alcohol availability over time was approximated by the number of extant alcohol licences, categorised by outlet type: drinking establishments, eateries, takeaways, off-sales and 'other'. Harm was quantified drawing on law enforcement intelligence that recorded ARV. A linked data set was analysed using negative binomial regression, contrasting cumulative impact zones (CIZ)-a common alcohol control policy-with non-CIZ geographies. RESULTS: Each licensed drinking establishment was associated with a 1.6% (95% CI 0.7% to 2.6%; p=0.001) increase in ARV, respectively. 'Other' outlets had a protective effect and were associated with a 1.8% (95% CI 1.0% to 2.5%; p<0.001) decrease in ARV. CONCLUSION: This study provides direct evidence for an association between alcohol-related harm and licensed premises. The varying associations between outlet type and ARV provide local public health stakeholders with an evidence base upon which to advocate for licensing policies that diversify alcohol availability.