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An Early Intervention in Psychosis (EIP) programme aims to engage patients in early assessment and phase-specific interventions which are the key elements of the Irish National Clinical Programme for psychosis. This study aims to describe and review the EIP programme offered by Cork’s North Lee Mental Health Services over a 5-year period.
A retrospective descriptive study design was adopted to describe and review the EIP programme, patient demographics and treatments offered in the service over a 5-year period.
A total of 139 patients were accepted into the programme over the 5-year period. The mean age of onset was 30 years (median = 28, SD = 9.9), and the mean duration of untreated psychosis was 8 months (median = 2.5, SD = 15.3). Two-thirds of patients were single on initial assessment, had a history of substance misuse and were unemployed. The majority of the cohort engaged with the keyworkers and occupational therapy but did not complete the full psychological or family programmes offered. Hospital admission was required for 12% of the cohort.
Patients experiencing their first episode of psychosis can successfully be treated in the community with appropriate professional and family support. However, deficiencies were noted in physical health monitoring, as well as in the availability and engagement with family and psychological therapies. Properly resourced early interventions in psychosis teams are necessary to deliver services at internationally recognised standards.
Introduction: The number of seniors presenting to emergency departments after a fall is increasing. Head injury concerns in this population often leads to a head CT scan. The CT rate among physicians is variable and the reasons for this are unknown. This study examined the role of patient characteristics and country of practice in the decision to order a CT. Methods: This study used a case-based survey of physicians across multiple countries. Each survey included 9 cases pertaining to an 82-year old man who falls. Each case varied in one aspect compared to a base case (aspirin, warfarin, or rivaroxaban use, occipital hematoma, amnesia, dementia, and fall with no head trauma). For each case, participants indicated how “likely” they were to order a head CT scan, measured on a 100-point scale. A response of 80 or more was defined a priori as ‘likely to order a CT scan’. The survey was piloted among emergency residents for feedback on design and comprehension, and was published in French and English. Recruitment was through the Canadian Association of Emergency Physicians, Twitter and CanadiEM. For each case we compared the proportion of physicians who were ‘likely to scan’ with relative to the base case. We also compared the proportion of participants who were ‘likely to scan’ each case in the USA, UK and Australia, relative to Canada. Results: Data was collected from 484 respondents (Canada-308, USA-64, UK-67, Australia-27, and 18 from other countries). Social media distribution limited our ability to estimate of the response rate. Physicians were most likely to scan in the anticoagulation cases (90% likely to order a scan compared to 36% for the base case (p = <0.001)). Other features associated with increased scans were occipital hematoma (48%), multiple falls (68%), and amnesia (68%) (all p < 0.005). Compared to Canada, US physicians were more likely to order CT scans for all cases (p = <0.05). Compared to Canada, UK physicians were significantly less likely to order CT for patients in every case except in the patient with amnesia. Finally, Australian physicians differed from Canada only for the occipital hematoma case where they were significantly more likely to order CT scan. Conclusion: Anticoagulation, amnesia and a history of multiple falls appear to drive the ordering a head CT scan in elderly patients who had fallen. We observed variations in practice between countries. Future clinical decision rules will likely have variable impact on head CT scan rates depending on baseline practice variation.
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Synthesis of Ni and Zn substituted nano-greigite,
Fe3S4, is achieved from single source
diethyldithiocarbamato precursor compounds, producing particles typically
50–100 nm in diameter with plate-like pseudohexagonal morphologies. Up to 12
wt.% Ni is incorporated into the greigite structure, and there is evidence
that Zn is also incorporated but Co is not substituted into the lattice. The
Fe L3 X-ray absorption spectra for these materials have a narrow
single peak at 707.7 eV and the resulting main X-ray magnetic circular
dichroism (XMCD) has the same sign at 708.75 eV. All XMCD spectra also have
a broad positive feature at 711 eV, a characteristic of covalent mixing. The
greigite XMCD spectra contrast with the three clearly defined XMCD site
specific peaks found in the ferrite spinel, magnetite. The Fe
L2,3X-ray absorption spectra and XMCD spectra of the
greigite reflect and reveal the high conductivity of greigite and the very
strong covalency of the Fe–S bonding. The electron hopping between
Fe3+ and Fe2+ on octahedral sites results in an
intermediate oxidation state of the Fe in the Oh site of
Fe2.5+ producing an effective formula of [Fe3+
↑]A-site[2Fe2.5+ ↓]B-siteS42–]. The Ni L2,3 X-ray absorption spectra and XMCD reveal substitution on the
Oh site with a strongly covalent character and an
oxidation state <Ni1.5+ in a representative formula
[Fe3+ ↑]A[[(2 – x)Fe2.5+
Accurate genomic analyses are predicated on access to a large quantity of accurately genotyped and phenotyped animals. Because the cost of genotyping is often less than the cost of phenotyping, interest is increasing in generating genotypes for phenotyped animals. In some instances this may imply the requirement to genotype older animals with greater phenotypic information content. Biological material for these older informative animals may, however, no longer exist. The objective of the present study was to quantify the ability to impute 11 129 single nucleotide polymorphism (SNP) genotypes of non-genotyped animals (in this instance sires) from the genotypes of their progeny with or without including the genotypes of the progenys’ dams (i.e. mates of the sire to be imputed). The impact on the accuracy of genotype imputation by including more progeny (and their dams’) genotypes in the imputation reference population was also quantified. When genotypes of the dams were not available, genotypes of 41 sires with at least 15 genotyped progeny were used for the imputation; when genotypes of the dams were available, genotypes of 21 sires with at least 10 genotyped progeny were used for the imputation. Imputation was undertaken exploiting family and population level information. The mean and variability in the proportion of genotypes per individual that could not be imputed reduced as the number of progeny genotypes used per individual increased. Little improvement in the proportion of genotypes that could not be imputed was achieved once genotypes of seven progeny and their dams were used or genotypes of 11 progeny without their respective dam’s genotypes were used. Mean imputation accuracy per individual (depicted by both concordance rates and correlation between true and imputed) increased with increasing progeny group size. Moreover, the range in mean imputation accuracy per individual reduced as more progeny genotypes were used in the imputation. If the genotype of the mate of the sire was also used, high accuracy of imputation (mean genotype concordance rate per individual of 0.988), with little additional benefit thereafter, was achieved with seven genotyped progeny. In the absence of genotypes on the dam, similar imputation accuracy could not be achieved even using genotypes on up to 15 progeny. Results therefore suggest, at least for the SNP density used in the present study, that it is possible to accurately impute the genotypes of a non-genotyped parent from the genotypes of its progeny and there is a benefit of also including the genotype of the sire’s mate (i.e. dam of the progeny).
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.
Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.
Glioblastoma (GBM) is the most common brain cancer. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for MGMT protein-expression and ensuing temozolomide-resistance. Second-line treatment with bevacizumab has not improved overall survival (OS). Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent targeting N7-Guanine, thus MGMT-independently inducing interstrand cross-links, DNA double-strand breaks and cell-death in GBM cell-lines and cancer stem cells. VAL-083 is currently in Phase I/II clinical trial for recurrent GBM, post-TMZ and post-bevacizumab. In this Phase II clinical trial, the main goal is to assess the 9-month OS in MGMT-unmethylated, recurrent, bevacizumab-naive GBM. RATIONALE: The vast majority of GBM patients experience recurrent/progressive disease within a year from initial diagnosis and median survival after recurrence is 3-9 months. Chemotherapy regimens for these patients are lacking and there is a significant unmet medical need. Given VAL-083’s novel alkylating mechanism, promising clinical benefit, and favorable safety profile, a trial studying VAL-083 in MGMT-unmethylated recurrent GBM is warranted. METHOD: Randomized, non-comparative biomarker-driven Phase II clinical trial in MGMT-unmethylated GBM patients at first recurrence/progression, prior to bevacizumab. 48 patients will be randomized to receive VAL-083 or “standard-of-care” salvage drug lomustine. 32 patients will receive VAL-083 40mg/m2/day on days 1,2,3 of a 21-day cycle. 16 patients will receive lomustine 90 mg/m2/day on day 1 of a 42-day cycle. Patients will be followed until death or for at least 9 months from enrollment, whichever occurs earlier. Survival will be compared to the BELOB trial for recurrent MGMT-unmethylated GBM patients treated with lomustine.
A radiochemical 71Ga−71 Ge experiment to determine the integral flux of neutrinos from the sun has been constructed at the Baksan Neutrino Observatory in the USSR. Measurements have begun with 30 tonnes of gallium. The experiment is being expanded with the addition of another 30 tonnes. The motivation, experimental procedures, and present status of this experiment are presented.
The variability of CD-24 7599 (V=11.48 mag) was discovered by JCC during observing run XCOV7 of the Whole Earth Telescope (WET, Nather et al. 1990) network in February, 1992. The star was observed as an additional target and 117 hours of high-quality temporal spectroscopic observations were obtained.
Our analysis of these data revealed the presence of 7 independent pulsation modes between 27.0 and 38.1 cycles per day (313 – 441 μHz) with semiamplitudes of 2.1 – 10.2 milli-modulation amplitudes (mma). We showed that peaks at linear combination frequencies detected in the power spectra were not due to eigenmodes excited to visible amplitude by resonant mode coupling.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.