Public History and the study of Law: reviewing The Limehouse Golem (2017). Directed by Juan Carlos Medina [film]. 109 min. UK. Production: Lipsync Post, Number 9 Films.

This is an interdisciplinary discussion, looking at the use of popular history for the critical understanding of the reconstruction of crime and patriarchal hierarchy. By way of reviewing the recent movie The Limehouse Golem, it illustrates the significance of theoretically engaging with a period crime fiction movie. It is argued that this assessment is less relevant in terms of producing historical understanding; rather, what may be a fiction, reveals instead our own contemporary cultural fixations

Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers

Patients and methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014-October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy

The associations between sedentary behaviour and mental health among adolescents:A systematic review

Background: With technological developments and modernised sedentary lifestyles has come an increase in diseases associated with inactivity such as obesity and other non-communicable diseases. Emerging evidence suggests that time spent sedentary may also interact with mental health. This systematic review examined the associations between sedentary behaviour and mental health problems among adolescents. Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and applied a quality assessment tool for quantitative studies to identity best available evidence. Following stringent search strategy of the databases; Cumulative Index to Nursing and Allied Health Literature, Global Health, Health Source: Nursing and Academic Edition, MEDLINE, PsychARTICLES and PsycINFO, we identified 32 articles eligible for review. Results: All studies reported leisure screen time among adolescents, and two thirds of identified studies examined depressive symptomatology. Other mental health measures were; anxiety symptoms, self-esteem, suicide ideation, loneliness, stress, and psychological distress. Strong consistent evidence was found for the relationship between both depressive symptomatology and psychological distress, and time spent using screens for leisure. Moderate evidence supported the relationship between low self-esteem and screen use. Poorer mental health status was found among adolescents using screen time more than 2-3 h per day, and gender differences exist. Essential information was missing for quality of evidence including heterogeneity in mental health and screen time-based measures, and self-report data collection methods. Conclusions: The findings are of particular significance given the global public health concern of lifestyle-attributed diseases and the possibility for novel approaches to mental health. Future research should examine the psychological impact of reducing time spent using screens for leisure among adolescents, whilst accounting for possible confounding factors such as physical activity and dietary behaviours. It is critical that the reciprocal relationship between lifestyle behaviours and mental health is represented in both the psychiatric and public health forum

Iontophoretic delivery of dexamethasone phosphate for non-infectious, non-necrotising anterior scleritis, dose-finding clinical trial

AbstractCurrently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects. This first-in-human randomised, double-masked, dose-escalating study of iontophoretic administration of dexamethasone phosphate for scleritis suggests the treatment to be well tolerated and safe (within the limitations of the 18 patients sample size). There was a suggestion of efficacy in the lowest (1.2 mA/min at 0.4 mA) dose group (corresponding to the superficial location of scleritis compared with anterior uveitis), with 5/7 eyes meeting the primary efficacy outcome within 28 days. Our results suggest iontophoretic delivery of corticosteroids is a promising potential treatment for scleritis, with favourable safety and preliminary efficacy results in this phase 1 trial.Trial registration numberNCT01059955

Fleck-like lesions in <i>CEP290-associated</i> leber congenital amaurosis: a case series

To provide a detailed ophthalmic phenotype of a small cohort of patients with Leber Congenital Amaurosis (LCA) caused by mutations in CEP290 (CEP290-LCA) with a focus on elucidating the origin of yellow-white lesions observed in 30% of patients with this condition. This is a retrospective review of records of five patients with CEP290-LCA. Patients had comprehensive ophthalmic evaluations. Visual function was assessed with full-field electroretinograms (ffERGs) and full-field sensitivity testing (FST). Multimodal imaging was performed with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation wavelengths. All patients showed relative structural preservation of the foveal and near midperipheral retina separated by a pericentral area of photoreceptor loss. Yellow-white, fleck-like lesions in an annular distribution around the near midperiphery co-localized with hyperreflective lesions on SD-OCT. The lesions located between the inner segment ellipsoid signal and the apical retinal pigment epithelium (RPE). The inner retina was normal. Longitudinal observations in one of the patients indicates the abnormalities may represent an intermediate stage in the degenerative process between the near normal appearing retina previously documented in young CEP290-LCA patients and the pigmentary retinopathy observed along the same region in older individuals. We speculate that fleck-like lesions in CEP290-LCA correspond to malformed, rudimentary or degenerated, including shed, photoreceptor outer segments. The topography and possible origin of the abnormalities may inform the planning of evolving genetic therapies for this disease.</p

Brief intervention to prevent hazardous drinking in young people aged 14–15 in a high school setting (SIPS JR-HIGH): study protocol for a randomized controlled trial

Background: Whilst the overall proportion of young people drinking alcohol in the United Kingdom has decreased in recent years, those who do drink appear to drink a larger amount, and more frequently. Early and heavy drinking by younger adolescents is a significant public health problem linked to intellectual impairment, increased risk of injuries, mental health issues, unprotected or regretted sexual experience, violence, and sometimes accidental death, which leads to high social and economic costs. This feasibility pilot trial aims to explore the feasibility of delivering brief alcohol intervention in a school setting with adolescents aged 14 and 15 and to examine the acceptability of study measures to school staff, young people and parents. Methods and design: Seven schools across one geographical area in the North East of England will be recruited. Schools will be randomly allocated to one of three conditions: provision of an advice leaflet (control condition, n= 2 schools); a 30-minute brief interactive session, which combines structured advice and motivational interviewing techniques delivered by the school learning mentor (level 1 condition, n= 2 schools); and a 60-minute session involving family members delivered by the school learning mentor (level 2 condition, n= 3 schools). Participants will be year 10 school pupils (aged 14 and 15) who screen positively on a single alcohol screening question and who consent to take part in the trial. Year 10 pupils in all seven schools will be followed up at 6 and 12 months. Secondary outcome measures include the ten-question Alcohol-Use Disorders Identification Test. The EQ-5D-Y and a modified short service use questionnaire will inform the health and social resource costs for any future economic evaluation. Young people recruited into the trial will also complete a 28-day timeline follow back questionnaire at 12-month follow-up. A qualitative evaluation (with young people, school staff, learning mentors, and parents) will examine facilitators and barriers to the use of screening and brief intervention approaches in the school setting in this age group