Postcode lottery? Hospital transfers from one London prison and responsible catchment area

Aims and method To consider the link between responsible commissioner and delayed prison transfers. All hospital transfers from one London prison in 2006 were audited and reviewed by the prisoner's borough of origin. Results Overall, 80 prisoners were transferred from the audited prison to a National Health Service (NHS) facility in 2006: 26% had to wait for more than 1 month for assessment by the receiving hospital unit and 24% had to wait longer than 3 months to be transferred. These 80 individuals were the responsibility of 16 different primary care trusts. Of the delayed transfer cases (n=19), the services commissioned by three primary care trusts were responsible for the delays. Clinical implications There are significant differences in performance between different primary care trusts related to hospital transfers of prisoners, with most hospitals able to admit urgent cases within 3 months. This suggests that a postcode lottery operates for prisoners requiring hospital transfer. Data from prison services may be useful in monitoring and improving the performance of local NHS services

Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri

Background The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. Results Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. Conclusions In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.publishedVersio

Forming-free resistive switching of tunable ZnO films grown by atomic layer deposition

Undoped ZnO thin films with tunable electrical properties have been achieved by adjusting the O2 plasma time in the plasma enhanced atomic layer deposition process. The structural, compositional and electrical properties of the deposited ZnO films were investigated by various characterization techniques. By tuning the plasma exposure from 2 to 8 s, both resistivities and carrier concentrations of the resultant ZnO films can be modulated by up to 3 orders of magnitude. Forming-free TiN/ZnO/TiN resistive memory devices have been achieved by choosing the ZnO film with the plasma exposure time of 6 s. This deposition method offers a great potential for producing other un-doped metal oxides with tunable properties as well as complex multilayer structures in a single deposition

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

First-to-file rule: Is it constitutional?

Republic Act 8293, also known as the Intellectual Property Code, took effect last January 1, 1998. It amended Republic Act 165 (Patent Law), Republic Act 166 (Trademark Law) and Presidential Decree 49 (Copyright Law). There were several changes made in our patent law. One of its changes is the shift from first-to-invent to the first-to-file rule for patent registration. Said shift was done in view of harmonization, in compliance with the TRIPS Agreement.This paper is a study of whether or not the shift in the system of patent registration: first-to-invent to first-to-file rule is violative of our Constitution. The Constitutional provisions regarding science and technology will be discussed in light of the Intellectual Property Code. Does the first-to-file rule in patent registration carry out the State\u27s objective to prioritize inventions and research & development? Does the first-to-file violate the exclusive rights of scientists and inventors

Prison health-care wings: psychiatry's forgotten frontier?

Background There is worldwide evidence of high rates of mental disorder among prisoners, with significant co‐morbidity. In England and Wales, mental health services have been introduced from the National Health Service to meet the need, but prison health‐care wings have hardly been evaluated. Aims/hypotheses To conduct a service evaluation of the health‐care wing of a busy London remand (pre‐trial) prison and examine the prevalence and range of mental health problems, including previously unrecognised psychosis. Methods Service‐use data were collected from prison medical records over a 20‐week period in 2006–2007, and basic descriptive statistics were generated. Results Eighty‐eight prisoners were admitted (4.4 per week). Most suffered from psychosis, a third of whom were not previously known to services. Eleven men were so ill that they required emergency compulsory treatment in the prison under Common Law before hospital tranfer could take place. Over a quarter of the men required hospital transfer. Problem behaviours while on the prison health‐care wing were common. Conclusions and implications Prison health‐care wings operate front‐line mental illness triaging and recognition functions and also provide care for complex individuals who display behavioural disturbance. Services are not equivalent to those in hospitals, nor the community, but instead reflect the needs of the prison in which they are situated. There is a recognised failure to divert at earlier points in the criminal justice pathway, which may be a consequence of national failure to fund services properly. Hosptial treatment is often delayed. Copyright © 2010 John Wiley & Sons, Ltd

Vaccines for COVID-19: where do we stand in 2021?

As of July 2021, over 3 billion doses of a COVID-19 vaccines have been administered globally, and there are now 19 COVID-19 vaccines approved for use in at least one country. Several of these have been shown to be highly effective both in clinical trials and real-world observational studies, some of which have included special populations of interest. A small number of countries have approved a COVID-19 vaccine for use in adolescents or children. These are laudable achievements, but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries, with only 0.9% of people in low-income countries having received at least one dose of a COVID-19 vaccine. Addressing this inequity is of critical importance and will result in better control of SARS-CoV-2 globally. Other challenges include: the reduced protection from COVID-19 vaccines against some strains of SARS-CoV-2, necessitating the development of variant specific vaccines; and uncertainties around the duration of protection from vaccine-induced immunity

Spoken word recognition in listeners with mild dementia symptoms

Background Difficulty understanding speech is a common complaint of older adults. In quiet, speech perception is often assumed to be relatively automatic. In background noise, however, higher-level cognitive processes play a more substantial role in successful communication. Cognitive resources are often limited in adults with dementia, which may therefore hamper word recognition. Objective The goal of this study was to determine the impact of mild dementia on spoken word recognition in quiet and noise. Methods Participants were adults aged 53–86 years with (n=16) or without (n=32) dementia symptoms as classified by a clinical dementia rating scale. Participants performed a word identification task with two levels of neighborhood density in quiet and in speech shaped noise at two signal-to-noise ratios (SNRs), +6 dB and +3 dB. Our hypothesis was that listeners with mild dementia would have more difficulty with speech perception in noise under conditions that tax cognitive resources. Results Listeners with mild dementia had poorer speech perception accuracy in both quiet and noise, which held after accounting for differences in age and hearing level. Notably, even in quiet, adults with dementia symptoms correctly identified words only about 80% of the time. However, phonological neighborhood density was not a factor in the identification task performance for either group. Conclusion These results affirm the difficulty that listeners with mild dementia have with spoken word recognition, both in quiet and in background noise, consistent with a key role of cognitive resources in spoken word identification. However, the impact of neighborhood density in these listeners is less clear

Assessment of daily light and ultraviolet exposure in young adults

Purpose: There are some limited reports, based on questionnaire data, which suggest that outdoor activity decreases the risk of myopia in children and may offset the myopia risk associated with prolonged near work. The aim of this study was to explore the relationship between near work, indoor illumination, daily sunlight and ultraviolet (UV) exposure in emmetropic and myopic University students, given that University students perform significant amounts of near work and as a group have a high prevalence of myopia. \ud \ud Methods: Participants were 35 students, aged 17 to 25 years who were classified as being emmetropic (n=13), or having stable (n=12) or progressing myopia (n=10). During waking hours on three separate days participants wore a light sensor data logger (HOBO) and a polysulphone UV dosimeter; these devices measured daily illuminance and accumulative UV exposure respectively; participants also completed a daily activity log. \ud \ud Results: No significant between group differences were observed for average daily illuminance (p=0.732), number of hours per day spent in sunlight (p=0.266), outdoor shade (p=0.726), bright indoor/dim outdoor light (p=0.574) or dim room illumination (p=0.484). Daily UV exposure was significantly different across the groups (p=0.003); with stable myopes experiencing the greatest UV exposure (versus emmetropes p=0.002; versus progressing myopes p=0.004). \ud \ud Conclusions: The current literature suggests there is a link between myopia protection and spending time outdoors in children. Our data provides some evidence of this relationship in young adults and highlights the need for larger studies to further investigate this relationship longitudinally