Female offending and the question of gender specificity

This thesis aims to present an examination of the issue of gender specificity and how it applies to understanding female offending. For several decades, a debate has existed in the literature between two fields, the feminist criminological and ‗risk-need-responsivity‘ camps, regarding the most appropriate way to assess and treat female offenders. A systematic review in chapter two examined factors associated with risk for reoffending in females. It demonstrated that while traditional approaches are adequate in predicting risk for recidivism, they do not appear to fully incorporate the complex presentation of females who offend. An empirical research project examining gender differences in violence subtypes in inpatients demonstrated that females who are instrumentally violent present with the most treatment needs in terms of history of victimisation and mental health needs. However, similarities are also noted between genders, with personality disorders being most predictive of instrumental violence in both males and females. Chapter four presents a critique of the Levenson Self Report Psychopathy scale (LSPS) which was utilised to help delineate gender differences in violent subtypes and is commonly used to assess self-reported traits for psychopathy. The review indicated that the LSPS may offer a reliable and valid way to assess traits associated with psychopathy. However, it is also noted that mixed findings regarding factor structure and potential gender issues suggest that tool should be used with some caveats in place. Results indicate that in the search for understanding gender differences in offending, an exploration regarding the expression of psychopathy and personality disorders across genders is integral. It is evident that the time has come to move beyond the gender specificity debate to work towards a more integrated approach to assessing and managing females who offend

The design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation

Abstract Background No standardised system of triage exists in Maternity Care and local audit identified this to be problematic. We designed, implemented and evaluated an Obstetric Triage System in a large UK maternity unit. This includes a standard clinical triage assessment by a midwife, within 15 min of attendance, leading to assignment to a category of clinical urgency (on a 4-category scale). This guides timing of subsequent standardised immediate care for the eight most common reasons for attendance. A training programme was integral to the introduction. Methods A mixed methods evaluation was conducted. A structured audit of 994 sets of maternity notes before and after implementation identified the number of women seen within 15 min of attendance. Secondary measures reviewed included time to subsequent care and attendance. An inter-operator reliability study using scenarios was completed by midwives. A focus group and two questionnaire studies were undertaken to explore midwives’ views of the system and to evaluate the training. In addition a national postal survey of practice in UK maternity units was undertaken in 2015. Results The structured audit of 974/992 (98%) of notes demonstrated an increase in the number of women seen within 15 min of attendance from 39% before implementation to 54% afterwards (RR (95% CI) 1.4 (1.2, 1.7) p = <0.0001). Excellent inter-operator reliability (ICC 0.961 (95% CI 0.91–0.99)) was demonstrated with breakdown showing consistently good rates. Thematic analysis of focus group data (n = 12) informed the development of the questionnaire which was sent to all appropriate midwives. The response rate was 53/79 (67%) and the midwives reported that the new system helped them manage the department and improved safety. The National Survey (response rate 85/135 [63%]) demonstrated wide variation in where women are seen and staffing models in place. The majority of units 69/85 (81%) did not use a triage system based on clinical assessment to prioritise care. Conclusions This obstetric triage system has excellent inter- operator reliability and appears to be a reliable way of assessing the clinical priority of women as well as improving organisation of the department. Our survey has demonstrated the widespread need for implementation of such a system

Caracterización de biomarcadores en la recurrencia post-quirúrgica de la enfermedad de Crohn: valor predictivo e implicación patogénica

A pesar de un conocimiento cada vez mayor sobre la patogenia de la enfermedad de Crohn (EC) y el desarrollo de esquemas de tratamiento más potentes que incluyen los fármacos biológicos, las tasas de cirugía en estos pacientes siguen siendo elevadas. Así, un 50-60% de los pacientes con EC requieren de una resección intestinal en los primeros 10 años tras el diagnóstico, y un 25% de éstos acabarán requiriendo de una segunda cirugía dentro de los 5 años siguientes. Dado que la cirugía no supone un tratamiento curativo, la reaparición de lesiones tras la resección de todo el tramo intestinal afecto (fenómeno conocido como recurrencia post-quirúrgica) es muy frecuente en estos pacientes, a pesar incluso de la intervención terapéutica. Entre los tratamientos empleados para prevenir la recurrencia de la EC se incluyen la mesalazina, los inmunomoduladores tiopurínicos y en la actualidad los fármacos biológicos o anti-TNF. En los últimos años, diferentes estudios han confirmado la eficacia del tratamiento biológico en la prevención de la recurrencia, especialmente en pacientes de alto riesgo, con una tendencia actual a su introducción precoz tras la cirugía. Sin embargo, estos tratamientos implican una tasa nada desdeñable de efectos adversos, además de un elevado coste por paciente. Por otro lado, no está claramente establecido qué pacientes se benefician de un tratamiento más intensivo tras la cirugía ni la duración de mantenimiento del mismo. Por todo ello, surge la necesidad de desarrollar nuevas herramientas y estrategias que permitan identificar el riesgo de una recurrencia precoz tras la cirugía y optimizar el manejo clínico de estos pacientes. En el momento actual, la ileocolonoscopia continúa siendo el gold estándar para el seguimiento y diagnóstico de la recurrencia, a pesar de suponer una técnica invasiva, costosa, no exenta de riesgos y en general mal tolerada por los pacientes. Esto es así porque hasta el momento no disponemos de buenos marcadores predictores de recurrencia tras la cirugía, y porque la utilidad de la valoración clínica y analítica para el diagnóstico de la recurrencia es limitada. Por este motivo, existe especial interés en el empleo de biomarcadores no invasivos y de fácil obtención, que sirvan para monitorizar a estos pacientes tras la cirugía y permitan detectar precozmente el desarrollo de recurrencia. En este sentido, entre los marcadores fecales, la calprotectina ha mostrado previamente gran utilidad clínica en diferentes escenarios de la enfermedad y, aunque su papel en el contexto post-quirúrgico no ha sido evaluado en profundidad en series amplias de carácter prospectivo, la evidencia disponible sugiere también su utilidad como marcador de recurrencia, aunque quedan aspectos por definir con claridad para su aplicación en la práctica. La existencia de otros posibles biomarcadores en sangre periférica tampoco ha sido explorada en este escenario de la EC. Por otro lado, el escenario clínico de la recurrencia supone una condición patogénica de novo, por lo que los pacientes con EC intervenidos constituyen el mejor modelo natural in vivo para poder estudiar e identificar los posibles mecanismos patogénicos implicados en la reaparición de la enfermedad. Con todo ello, el objetivo de la presente tesis doctoral se centra en la caracterización prospectiva de marcadores no invasivos, a partir de muestras biológicas de fácil obtención (sangre periférica y heces), que dispongan de capacidad predictiva de recurrencia en el contexto post-quirúrgico de la EC, y permitan identificar y monitorizar los cambios que acontecen en el desarrollo de la inflamación de novo. Igualmente, se pretende conocer el perfil de la respuesta inmune que dirige este proceso y los posibles elementos epigenéticos reguladores, así como su implicación patogénica en la génesis de la recurrencia. Finalmente, se plantea el desarrollo de una herramienta de predicción (índice predictivo combinado) empleando los biomarcadores identificados, con potencial aplicación en la práctica clínica para un mejor manejo de estos pacientes.Despite increasing awareness of the pathogenesis of Crohn's disease (CD) and the development of more potent therapeutic regimens including biological drugs, surgery rates in these patients remain high. Thus, 50-60% of patients with CD require bowel resection in the first 10 years after diagnosis, and 25% of these patients will require a second surgery within the next 5 years. Since surgery is not curative, the appearance of new intestinal lesions after resection is very frequent in these patients despite the therapeutic intervention. This phenomenon is known as post-operative recurrence. Treatments used to prevent recurrence of CD after surgery include mesalazine, thiopurines, and nowadays, biological or anti-TNF drugs. In recent years, several studies have confirmed the efficacy of biological treatment in the prevention of recurrence, especially in high-risk patients, with a current trend towards their early introduction after surgery. However, these drugs imply a not insignificant rate of adverse effects, in addition to a high cost per patient. On the other hand, it is not clearly established which patients benefit from a more intensive treatment after surgery or the duration of maintenance of the same. Therefore, the need arises to develop new tools and strategies to identify the risk of an early recurrence and to optimize the clinical management of these patients. Currently, ileocolonoscopy continues to be the gold standard for the follow-up and diagnosis of recurrence, despite being an invasive technique, expensive, non-risk-free and generally poorly tolerated by patients. This is because we do not have good predictive markers of recurrence after surgery until now, and because the usefulness of clinical and analytical assessment for the diagnosis of recurrence is limited. For this reason, there is a special interest in the use of non-invasive and easily obtained biomarkers, which serve to monitor these patients after surgery and allow early detection of post-operative recurrence. In this sense, fecal markers such as calprotectin have previously shown great clinical utility in different scenarios of the disease. In the post-surgical context, available evidence also suggests its potential utility as a marker of recurrence, although some aspects for its application in clinical practice remain to be clearly defined. Other possible biomarkers in peripheral blood have also not been explored in this EC scenario. On the other hand, post-operative recurrence supposes a new pathogenic condition, so that the CD patients underwent surgery are the best natural model in vivo to study and identify the pathogenic mechanisms involved in the reappearance of the disease. The aim of the present study is the prospective characterization of non-invasive markers in peripheral blood and feces, which have a predictive capacity for post-operative recurrence in CD, to identify and monitor the changes that occur in the development of the novo inflammation. Likewise, we intend to know the profile of the immune response that leads this process and possible regulatory epigenetic elements, as well as its pathogenic implication in the genesis of recurrence. Finally, we propose the development of a predictive tool (predictive combined index) using the identified biomarkers, with potential application in clinical practice for a better management of these patients

Additional file 1: of The design and implementation of an obstetric triage system for unscheduled pregnancy related attendances: a mixed methods evaluation

Baseline characteristics of women who attended Triage (DOCX 190 kb

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy

Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset &gt;2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as Definitive, 4 (11%) as Moderate and 1 (3%) as Limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

PURPOSE:: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. METHODS:: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25-30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. RESULTS:: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). CONCLUSION:: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. © 2011 Lippincott Williams &amp; Wilkins

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health