Considering community care in public health responses: A national study regarding palliative care during a prolonged coronavirus disease 2019 lockdown.

OBJECTIVE: To describe changes in palliative care characteristics, utilisation and outcomes in Victoria during a period of enhanced public health management and a prolonged lockdown due to coronavirus disease 2019. METHODS: A national retrospective cohort study with palliative care service setting comparisons in Victoria and other mainland states was conducted. RESULTS: Analysis of 48 non-Victorian services (n=53,428 patients) and 20 Victorian services (n=31,125 patients) showed that for community services, patient volume, average length of stay, functional dependency and the proportion of admissions in a deteriorating phase increased during the lockdown in Victoria, yet little changed in comparator states. Regarding inpatient services, the management of family/carer problems remained constant in comparator states, yet substantial fluctuations in outcomes in Victoria were observed. CONCLUSIONS: As health systems adapt to changing circumstances during the pandemic, the ability to upscale community services is critical. Addressing the implications of shifting inpatient care to the community needs attention. IMPLICATIONS FOR PUBLIC HEALTH: Our study highlights the need to ensure community care providers are adequately considered within public health management responses. 'Joined up' policy and implementation across care settings are essential, especially as major barriers to infection control and increased utilisation may be evident in the community during the coronavirus disease 2019 pandemic.

Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development.

Novel genetically modified biological control products (referred to as "GM biocontrol products") are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.

An image-based eyelid lesion management service-evaluation of a pilot.

BACKGROUND/AIMS: Oculoplastics is a predominantly visual specialty and many of the pathologies can be diagnosed based on external appearance. An image-based eyelid lesion management service was piloted to reduce the number of patients who would require outpatient clinic review. The aim of this study was to determine its accuracy and feasibility, both as a hospital-based and community optometrist-based service. If successful, the service was envisaged to significantly reduce the number of patients that require face-to-face (F2F) review, in accordance with current post-COVID-19 principles of social distancing. METHODS: Patients with lid lesions attending an oculoplastics clinic were assessed by consultant oculoplastic surgeons in an F2F consultation (Arm A). The lesions were photographed by a professional clinical photographer (Arm B) and by an optometrist with a handheld digital camera (Arm C). These images were reviewed by independent consultants masked to the outcome of the F2F clinical encounter. Data were collected prospectively including patient demographics, diagnosis, suspicion of malignancy and management. The image-based clinic results were compared to the F2F clinic results. RESULTS: Ninety-five patients were included. Clinical diagnoses were compared for intra-observer variability and substantial agreement was demonstrated between gold-standard F2F clinic visit (Arm A) and Arm B (Ƙ = 0.708) and C (Ƙ = 0.776). There was no statistically significant difference in the rate of discharge and all cases of malignancy were either identified or flagged for F2F review in the image-based arms. CONCLUSION: This pilot demonstrated substantial diagnostic agreement of image-based diagnoses with F2F consultation and image review alone did not miss any cases of malignancy.

Morphological, optical and photovoltaic characteristics of MoSe2/SiOx/Si heterojunctions.

This work reports the effect of different processing parameters on the structural and morphological characteristics of MoSe2 layers grown by chemical vapour deposition (CVD), using MoO3 and Se powders as solid precursors. It shows the strong dependence of the size, shape and thickness of the MoSe2 layers on the processing parameters. The morphology of the samples was investigated by field emission scanning electron microscopy (FESEM) and the thickness of the deposited layers was determined by atomic force microscopy (AFM). Raman and photoluminescence (PL) spectroscopies were used to confirm the high quality of the MoSe2 layers. Surface composition was examined by photoelectron spectroscopy (XPS). Moreover, the MoSe2/SiOx/Si heterojunctions exhibit diode behaviour, with a rectification ratio of 10, measured at ±2.0 V, which is due to the p-i-n heterojunctions formed at the p-Si/SiOx/MoSe2 interface. A photovoltaic effect was observed with a short circuit current density (Jsc), open circuit voltage (VOC) and efficiency of -0.80 mA/cm2, 1.55 V and 0.5%, respectively. These results provide a guide for the preparation of p-i-n heterojunctions based on few-layer MoSe2 with improved photovoltaic response.

Subducting serpentinites release reduced, not oxidized, aqueous fluids.

The observation that primitive arc magmas are more oxidized than mid-ocean-ridge basalts has led to the paradigm that slab-derived fluids carry SO2 and CO2 that metasomatize and oxidize the sub-arc mantle wedge. We combine petrography and thermodynamic modelling to quantify the oxygen fugacity (fO2) and speciation of the fluids generated by serpentinite dehydration during subduction. Silicate-magnetite assemblages maintain fO2 conditions similar to the quartz-fayalite-magnetite (QFM) buffer at fore-arc conditions. Sulphides are stable under such conditions and aqueous fluids contain minor S. At sub-arc depth, dehydration occurs under more reducing conditions producing aqueous fluids carrying H2S. This finding brings into question current models in which serpentinite-derived fluids are the cause of oxidized arc magmatism and has major implications for the global volatile cycle, as well as for redox processes controlling subduction zone geodynamics.

Enhancing oxygen delivery to ovarian follicles by three different methods markedly improves growth in serum-containing culture medium.

Invitro ovarian follicle culture systems are routinely used to study folliculogenesis and may provide solutions for infertility. Mouse follicles are typically cultured in standard gas-impermeable culture plates under gas phase oxygen concentrations of 5% or 20% (v/v). There is evidence that these conditions may not provide adequate oxygenation for follicles cultured as non-attached intact units in medium supplemented with serum and high levels of FSH. Three different methods of enhancing follicle oxygenation were investigated in this study: increasing the gas phase oxygen concentration, inverting the culture plates and using gas-permeable culture plates. Follicles cultured under 40% O2 were significantly larger (P P P 2 . These effects were associated with reduced secretion of vascular endothelial growth factor (P P P invivo -matured follicles (~500µm in diameter). Such follicular development is not possible under hypoxic conditions.

Brachionus leydigii (Monogononta: Ploima) reported from the western basin of Lake Erie.

Several species of non-indigenous planktonic invertebrates have historically been introduced to the Laurentian Great Lakes. Previous introductions of non-indigenous planktonic invertebrates to the Great Lakes have been crustacean zooplankton, specifically Cladocera and Copepoda. This report documents the first known occurrence of Brachionus leydigii var. tridentatus (Zernov, 1901) in Lake Erie and possibly the first detection of a non-indigenous rotifer species in the Laurentian Great Lakes. The specimen was collected from a U.S. EPA monitoring station in the western basin of Lake Erie on April 4, 2016.

The walking dead: sequential nuclear and organelle destruction during hair development.

BACKGROUND: Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell 'death', or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle. OBJECTIVES: To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology. METHODS: Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining. RESULTS: A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe. CONCLUSIONS: We propose a model of stepwise living-dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining 'living' characteristic, thus completing the march from 'living' to 'dead' within the hair follicle.

Corrigendum to: Hypoxia limits mouse follicle growth in vitro.

Ovarian follicle culture is useful for elucidation of factors involved in the regulation of follicular function. We examined the effects of gas phase oxygen concentration, an oil overlay, serum type and medium supplementation with FSH, insulin-transferrin-selenium (ITS) and I-ascorbic acid on cultured preantral mouse follicle growth in a spherical, non-attached follicle culture system. Follicle growth in 5% oxygen was significantly (P<0.01) inferior to growth in 20% oxygen in terms of follicle diameter. This was likely due to hypoxia, as evidenced by significantly (P<0.05) increased follicle secretion of vascular endothelial growth factor (VEGF), a marker of cell hypoxia. Follicular growth was not (P>0.05) affected by an oil overlay, ITS supplementation or serum type. Culture in medium with 5% mouse serum, 1 IU mL-1 FSH, 25 µgmL-1 l-ascorbic acid and 20% oxygen without an oil overlay supported the growth of follicles to a maximum diameter of 380 µm in 6 days. Compared with mature preovulatory mouse follicles in vivo that often have diameters >500 µm within the same time frame, in vitro-grown follicles clearly exhibit limited growth. Thus, adequate oxygenation is an essential factor in the process of optimising follicle growth.

Detecting peatland drains with Object Based Image Analysis and Geoeye-1 imagery.

BACKGROUND: Peatlands play an important role in the global carbon cycle. They provide important ecosystem services including carbon sequestration and storage. Drainage disturbs peatland ecosystem services. Mapping drains is difficult and expensive and their spatial extent is, in many cases, unknown. An object based image analysis (OBIA) was performed on a very high resolution satellite image (Geoeye-1) to extract information about drain location and extent on a blanket peatland in Ireland. Two accuracy assessment methods: Error matrix and the completeness, correctness and quality (CCQ) were used to assess the extracted data across the peatland and at several sub sites. The cost of the OBIA method was compared with manual digitisation and field survey. The drain maps were also used to assess the costs relating to blocking drains vs. a business-as-usual scenario and estimating the impact of each on carbon fluxes at the study site. RESULTS: The OBIA method performed well at almost all sites. Almost 500 km of drains were detected within the peatland. In the error matrix method, overall accuracy (OA) of detecting the drains was 94% and the kappa statistic was 0.66. The OA for all sub-areas, except one, was 95-97%. The CCQ was 85%, 85% and 71% respectively. The OBIA method was the most cost effective way to map peatland drains and was at least 55% cheaper than either field survey or manual digitisation, respectively. The extracted drain maps were used constrain the study area CO2 flux which was 19% smaller than the prescribed Peatland Code value for drained peatlands. CONCLUSIONS: The OBIA method used in this study showed that it is possible to accurately extract maps of fine scale peatland drains over large areas in a cost effective manner. The development of methods to map the spatial extent of drains is important as they play a critical role in peatland carbon dynamics. The objective of this study was to extract data on the spatial extent of drains on a blanket bog in the west of Ireland. The results show that information on drain extent and location can be extracted from high resolution imagery and mapped with a high degree of accuracy. Under Article 3.4 of the Kyoto Protocol Annex 1 parties can account for greenhouse gas emission by sources and removals by sinks resulting from "wetlands drainage and rewetting". The ability to map the spatial extent, density and location of peatlands drains means that Annex 1 parties can develop strategies for drain blocking to aid reduction of CO2 emissions, DOC runoff and water discoloration. This paper highlights some uncertainty around using one-size-fits-all emission factors for GHG in drained peatlands and re-wetting scenarios. However, the OBIA method is robust and accurate and could be used to assess the extent of drains in peatlands across the globe aiding the refinement of peatland carbon dynamics .

Dental pain in the medical emergency department: a cross-sectional study.

The aim of this study was to examine the number of patients attending a medical emergency department (MED) with dental problems over a three-year period. This cross-sectional study was carried out as part of a service evaluation. Data were collected via a database search of patient attendances at the MED using free text and the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) for oral and dental diagnoses. Data were analysed using descriptive statistics, t-test and chi-squared tests. Over the three-year period, there were 2504 visits to the MED for dental-related complaints, accounting for 0·7% of all attendances. The majority of patients were male (53·9%), with a mean age of 29 (s.d. 19·4) years for men, and 32 (s.d. 19·7) years for females. The mean index of multiple deprivation per cent rank was 35·0%. The most common diagnosis was unspecified dental disorder. Ten per cent of dental attendances to MED were repeat attendances by the same patients. In conclusion, patient attendances at MED for dental problems account for 0.7% of all attendances. MED may not be the most appropriate place for these patients to attend, in terms of care pathways, and also for economic reasons. The reasons why patients attend MED for dental problems clearly warrant further research.

Are atypical lymphocytes present with viral influenza-like illnesses (ILIs) in hospitalized adults?

The purpose of this investigation was to determine if atypical lymphocytes were of diagnostic value in viral influenza-like illnesses (ILIs) in hospitalized adults during the influenza season. Are atypical lymphocytes present with viral ILIs in hospitalized adults? During the influenza season, hospitals are inundated with influenza and viral ILIs, e.g., human parainfluenza virus-3 (HPIV-3). Without specific testing, clinically, it is difficult to differentiate influenza from ILIs, and surrogate influenza markers have been used for this purpose, e.g., relative lymphopenia. The diagnostic significance of atypical lymphocytes with ILIs is not known. We retrospectively reviewed the charts of 35 adults admitted with pneumonia due to viral ILI. The diagnosis of 14 patients was by respiratory virus polymerase chain reaction (PCR). During the 2015 influenza A season with ILIs, atypical lymphocytes were not present in influenza A (H3N2) patients but atypical lymphocytes were present in some ILIs, particularly HPIV-3. With viral ILIs, atypical lymphocytes should suggest a non-influenza viral diagnosis.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

The role of ADAMTS-13 activity and complement mutational analysis in differentiating acute thrombotic microangiopathies.

UNLABELLED: ESSENTIALS: Molecular diagnostics has improved the differentiation of acute thrombotic microangiopathys (TMAs). Atypical hemolytic uremic syndrome may have features mimicking thrombotic thrombocytopenic purpura. We identified novel complement mutations and a high incidence of CD46, with favorable long term outcomes. Complement mutation analysis in TMA where the diagnosis is unclear and ADAMTS-13 activity is >10%. BACKGROUND: Differentiation of acute thrombotic microangiopathy (TMA) at presentation has historically been dependent on clinical parameters. Confirmation of thrombotic thrombocytopenic purpura (TTP) is increasingly reliant on demonstrating deficient ADAMTS-13 activity. The identification of alternative complement pathway abnormalities in atypical hemolytic uremic syndrome (aHUS), along with the proven efficacy of terminal complement inhibitors in treatment, has increased the need for rapid differentiation of TTP from aHUS. OBJECTIVES: We describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs. PATIENTS/METHODS: Fourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%. RESULTS: Of 14 aHUS patients, 11 (79%) had platelet counts < 30 × 10(9) /L during the acute phase. Median presenting creatinine level was 295 µmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 µmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported. CONCLUSIONS: We demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities.

The clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza A (H3N2) epidemic: the uniqueness of HPIV-3 mimicking influenza A.

During influenza epidemics, influenza-like illnesses (ILIs) viruses cocirculate with influenza strains. If positive, rapid influenza diagnostic tests (RIDTs) identify influenza A/B, but false-negative RIDTs require retesting by viral polymerase chain reaction (PCR). Patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. In adults, the most useful laboratory abnormalities in influenza include relative lymphopenia, monocytosis, and thrombocytopenia. Lymphocyte:monocyte (L:M) ratios may be even more useful. L:M ratios <2 have been used as a surrogate marker for influenza, but there are no longitudinal data on L:M ratios in hospitalized adults with viral ILIs. During the 2015 influenza A (H3N2) epidemic at our hospital, we reviewed our experience with L:M ratios in 37 hospitalized adults with non-influenza viral ILIs. In hospitalized adults with non-influenza A ILIs, the L:M ratios were >2 with human metapneumovirus (hMPV), rhinoviruses/enteroviruses (R/E), and respiratory syncytial virus (RSV), but not human parainfluenza virus type 3 (HPIV-3), which had L:M ratios <2. HPIV-3, like influenza, was accompanied by L:M ratios <2, mimicking influenza A (H3N2). In influenza A admitted adults, L:M ratios <2 did not continue for >3 days, whereas with HPIV-3, L:M ratios <2 persisted for >3 days of hospitalization.

ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is the most common neurobiological disorder in children, with a prevalence of ~6-7%1,2 that has remained stable for decades2. The social and economic burden associated with patients3, families, and broader systems (healthcare/educational) is substantial, with the annual economic impact of ADHD exceed $30 billion in the US alone4. Efficacy of pharmacotherapy in treating ADHD symptoms has generally been considerable with at least ¾ of individuals benefitting from pharmacotherapy, typically in the form of stimulants5. In this review, we begin by briefly reviewing the history of pharmacotherapy in relation to ADHD, before focusing (primarily) on the state-of-the-field on themes such as biophysiology, pharmacokinetics, and pharmacogenomics. We conclude with a summary of emerging clinical and research studies, particularly the potential role for precision therapy in matching ADHD patients and drug types.

Point of care optical diagnostic technologies for the detection of oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: Despite significant advances in treatment modalities, the 5 year survival rate in oral and oropharyngeal squamous cell carcinoma (SCC) is less than 60%. Clinical examination, white light endoscopy followed by blind biopsies and histopathological analysis remains the gold standard for diagnosis and surveillance. These modalities continue to have a limited diagnostic accuracy of less than 55%. METHODS: Novel optical-based diagnostic methods are promising new technologies for improving both screening and detection of cancer. This review will discuss their role in oral and oropharyngeal cancer detection with particular emphasis on optical imaging in oral and oropharyngeal cancer diagnosis, including the use of surface enhanced Raman spectroscopy, optical coherence tomography, fluorescence diagnosis, confocal laser endomicroscopy, confocal reflectance microscopy and narrow band imaging. RESULTS: Aided by the use of differing wavelengths of light, these methods are capable of detecting physical and biochemical changes that precede and mirror malignant change within tissue. CONCLUSION: Our review of the currently utilized optical diagnostic modalities suggests the possibility of a cost effective, point of care diagnosis that could facilitate early detection, reduce healthcare costs and improve patient survival and quality of life.

Hypoxia limits mouse follicle growth in vitro.

Ovarian follicle culture is useful for elucidation of factors involved in the regulation of follicular function. We examined the effects of gas phase oxygen concentration, an oil overlay, serum type and medium supplementation with FSH, insulin-transferrin-selenium (ITS) and l-ascorbic acid on cultured preantral mouse follicle growth in a spherical, non-attached follicle culture system. Follicle growth in 5% oxygen was significantly (P < 0.01) inferior to growth in 20% oxygen in terms of follicle diameter. This was likely due to hypoxia, as evidenced by significantly (P < 0.05) increased follicle secretion of vascular endothelial growth factor (VEGF), a marker of cell hypoxia. Follicular growth was not (P > 0.05) affected by an oil overlay, ITS supplementation or serum type. Culture in medium with 5% mouse serum, 1 IU mL-1 FSH, 25 µg mL-1 l-ascorbic acid and 20% oxygen without an oil overlay supported the growth of follicles to a maximum diameter of 380 µm in 6 days. Compared with mature preovulatory mouse follicles in vivo that often have diameters >500 µm within the same time frame, in vitro-grown follicles clearly exhibit limited growth. Thus, adequate oxygenation is an essential factor in the process of optimising follicle growth.