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Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
In the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers.
We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason.
We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life.
Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
The flora of Laos remains one of the least known within the Indo-Burma biodiversity hotspot. A floristic inventory was carried out in Phou Hin Poun National Biodiversity Conservation Area, an under-explored area of the Khammouane Limestone. This study provides a list of 27 taxa that are additions to the most recent country checklists. The Ebenaceae, Euphorbiaceae and Myrtaceae are the families with the highest species number. In this list, four species are endemic to Indochina (Cambodia, Laos and Vietnam): Cynometra dongnaiensis Pierre, Jasminum vidalii P.S.Green, Memecylon chevalieri Guillaumin and Pothos gigantipes Buchet ex P.C.Boyce. These results illustrate the paucity of our knowledge of the region surveyed and of the flora of Laos in general.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
This article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital.
The effect of laser intensity on characteristics of the plasma ablated from a low-Z (CH) planar target irradiated by a 250 ps, 0.438 µm laser pulse with the intensity of up to 1016 W/cm2 as well as on parameters of the laser-driven shock generated in the target for various scale-lengths of preformed plasma was investigated at the kilojoule Prague Asterix Laser System (PALS) laser facility. Characteristics of the plasma were measured with the use of 3-frame interferometry, ion diagnostics, an X-ray spectrometer, and Kα imaging. Parameters of the shock generated in a Cl doped CH target by the intense 3ω laser pulse were inferred by numerical hydrodynamic simulations from the measurements of craters produced by the shock in the massive Cu target behind the CH layer. It was found that the pressure of the shock generated in the plastic layer is relatively weakly influenced by the preplasma (the pressure drop due to the preplasma presence is ~10–20%) and at the pulse intensity of ~1016 W/cm2 the maximum pressure reaches ~80–90 Mbar. However, an increase in pressure of the shock with the laser intensity is slower than predicted by theory for a planar shock and the maximum pressure achieved in the experiment is by a factor of ~2 lower than predicted by the theory. Both at the preplasma absence and presence, the laser-to-hot electrons energy conversion efficiency is small, ~1% or below, and the influence of hot electrons on the generated shock is expected to be weak.
The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19·8, 95% confidence interval 4·0–∞). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.
Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear. The objective of this study was to assess prospectively the influence of cannabis use on transition to psychosis in people at ultra-high risk (UHR) for the disorder.
Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people (104 male, 78 female) at UHR for psychosis. Individuals were then followed clinically for 2 years to determine their clinical outcomes.
Lifetime cannabis use was reported by 134 individuals (73.6%). However, most of these individuals had stopped using cannabis before clinical presentation (n = 98, 73.1%), usually because of adverse effects. Among lifetime users, frequent use, early-onset use and continued use after presentation were all associated with an increase in transition to psychosis. Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently (frequent early-onset use: 25%; infrequent or late-onset use: 5%; χ21 = 10.971, p = 0.001). However, within the whole sample, cannabis users were no more likely to develop psychosis than those who had never used cannabis (cannabis use: 12.7%; no use: 18.8%; χ21 = 1.061, p = 0.303).
In people at UHR for psychosis, lifetime cannabis use was common but not related to outcome. Among cannabis users, frequent use, early-onset use and continued use after clinical presentation were associated with transition to psychosis.
A community outbreak of legionellosis occurred in Barrow-in-Furness, Cumbria, during July and August 2002. A descriptive study and active case-finding were instigated and all known wet cooling systems and other potential sources were investigated. Genotypic and phenotypic analysis, and amplified fragment length polymorphism of clinical human and environmental isolates confirmed the air-conditioning unit of a council-owned arts and leisure centre to be the source of infection. Subsequent sequence-based typing confirmed this link. One hundred and seventy-nine cases, including seven deaths [case fatality rate (CFR) 3·9%] were attributed to the outbreak. Timely recognition and management of the incident very likely led to the low CFR compared to other outbreaks. The outbreak highlights the responsibility associated with managing an aerosol-producing system, with the potential to expose and infect a large proportion of the local population and the consequent legal ramifications and human cost.
Digital signal processing is one of many valuable tools for suppressing unwanted signals or inter-ference. Building hardware processing engines seems to be the way to best implement some classes of interference suppression but is, unfortunately, expensive and time-consuming, especially if several miti-gation techniques need to be compared. Simulations can be useful, but are not a substitute for real data. CSIRO’s Australia Telescope National Facility has recently commenced a ‘software radio telescope’ project designed to fill the gap between dedicated hardware processors and pure simulation. In this approach, real telescope data are recorded coherently, then processed offline. This paper summarises the current contents of a freely available database of base band recorded data that can be used to experiment with signal processing solutions. It includes data from the following systems: single dish, multi-feed receiver; single dish with reference antenna; and an array of six 22 m antennas with and without a reference antenna. Astronomical sources such as OH masers, pulsars and continuum sources subject to interfering signals were recorded. The interfering signals include signals from the US Global Positioning System (GPS) and its Russian equivalent (GLONASS), television, microwave links, a low-Earth-orbit satellite, various other transmitters, and signals leaking from local telescope systems with fast clocks. The data are available on compact disk, allowing use in general purpose computers or as input to laboratory hardware prototypes.
The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.