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Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.
In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.
Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.
Clinical correspondence between general practitioners and specialists remains fundamental to the process of referral from primary care and transmission of management advice from consultants.
Discrepancies over medication records for patients with mental illness living in community were highlighted by a previous audit and recommendation for improvement were accepted and implemented by the trust.
An audit of the documentation of patient's medications in the Psychiatric clinic letters compared to the general practitioners records was done two years back and several recommendations were made to improve the communication.
The aim of this study was to examine if the recommendations from the previous audit was implemented and if the quality of communication about medication conveyed by the Psychiatrist to the General Practitioner improved.
Latest Psychiatric clinic letter of 50 patients were randomly selected from the computer database and they were checked against the latest GP records.The expectation is that the Psychiatric and GP records would correspond 100%.
This re-audit revealed most of the recommendations from the previous audit were implemented and as a result of that, the numbers of errors were reduced. However there were still significant errors detected including wrong medication, omission and incorrect dosage, schedule and frequency.
Objective. To identify clinically useful predictors of adherence to medication among persons with schizophrenia. Method. We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory. Results. Less than 25% of consecutive admissions reported being fully compliant. Drug attitudes were the best predictor of regular compliance, symptomatology the best predictor of noncompliance, and memory the best predictor of partial compliance with neuroleptic medication. Conclusions. These data emphasise the complexity of factors that influence whether a person adheres to his medication regimen. Furthermore, they suggest that these factors may vary within the same person over time.
The long-term effects of pediatric concussion on white matter microstructure are poorly understood. This study investigated long-term changes in white matter diffusion properties of the corpus callosum in youth several years after concussion.
Participants were 8–19 years old with a history of concussion (n = 36) or orthopedic injury (OI) (n = 21). Mean time since injury for the sample was 2.6 years (SD = 1.6). Participants underwent diffusion magnetic resonance imaging, completed cognitive testing, and rated their post-concussion symptoms. Measures of diffusivity (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from white matter tracts in the genu, body, and splenium regions of the corpus callosum. The genu and splenium tracts were further subdivided into 21 equally spaced regions along the tract and diffusion values were extracted from each of these smaller regions.
White matter tracts in the genu, body, and splenium did not differ in diffusivity properties between youth with a history of concussion and those with a history of OI. No significant group differences were found in subdivisions of the genu and splenium after correcting for multiple comparisons. Diffusion metrics did not significantly correlate with symptom reports or cognitive performance.
These findings suggest that at approximately 2.5 years post-injury, youth with prior concussion do not have differences in their corpus callosum microstructure compared to youth with OI. Although these results are promising from the perspective of long-term recovery, further research utilizing longitudinal study designs is needed to confirm the long-term effects of pediatric concussion on white matter microstructure.
The current study evaluated growth performance and digestion responses of finishing bulls fed diets containing 825 g/kg flint maize [dry matter (DM) basis] ground to medium (1.66 mm; MG) or coarse particle sizes (2.12 mm; CG), with added monensin (26 mg/kg; DM basis; MON) or a blend of essential oils (BEO) + exogenous α-amylase (AM; 90 mg/kg + 560 mg/kg commercial product, respectively, DM basis). In Expt 1, 256 Nellore bulls were blocked by initial body weight (BW) (360 ± 11.7 kg) and assigned to 48 pens in a 2 × 2 factorial arrangement of treatments. Effect of a maize particle size × feed additive interaction was not detected for final BW, DM intake (DMI), average daily gain (ADG) and feed efficiency. The DMI was greater for bulls fed BEO + AM v. MON. Final BW and ADG tended to be greater for bulls fed CG than MG maize. An interaction was detected for hot carcass weight which was 11 kg heavier for bulls fed BEO + AM v. MON in diets containing CG, but not MG particle size. In Expt 2, four ruminally cannulated Nellore steers were offered the same treatments as Expt 1, in a 4 × 4 Latin Square design. Intake of most nutrients was greater for steers fed CG than steers fed MG maize. In summary, feeding bulls CG maize increased growth performance and carcass characteristics compared with MG. The combination of BEO + AM resulted in heavier carcass weights compared with MON supplementation when included in diets containing CG maize.
Integrating mental health care into HIV services is critical to addressing the high unmet treatment needs for people living with HIV and comorbid major depressive disorder. Introducing routine mental health screening at the primary health care level is a much needed diagonal approach to enhancing HIV care. In low-resource settings with a shortage of mental health care providers, eMental Health may provide a novel opportunity to attenuate this treatment gap and strengthen the health system.
To conduct formative health systems research on the implementation of routine depression screening using a digital tool – Mood in Retroviral Positive Individuals Application Monitoring (MIR + IAM) – in an HIV primary care setting in South Africa.
A Theory of Change (ToC) approach was utilised through individual and group session interviews to design an intervention that is embedded in the local context. Ten experts and local stakeholders were selected from the UK and South Africa. Data were analysed thematically using Atlas.ti to identify interventions, assumptions, barriers and facilitators of implementation.
The participants considered digital depression screening in HIV care services relevant for the improvement of mental health in this population. The six main themes identified from the ToC process were: (1) user experience including acceptability by patients, issues of patient privacy and digital literacy, and the need for a patient-centred tool; (2) benefits of the digital tool for data collection and health promotion; (3) availability of treatment after diagnosis; (4) human and physical resource capacity of primary health care; (5) training for lay health care workers; and (6) demonstration of the intervention's usefulness to generate interest from decision-makers.
Digital depression screening coupled with routine mental health data collection and analysis in HIV care is an applicable service that could improve the mental and physical health outcomes of this population. Careful consideration of the local health system capacity, including both workers and patients, is required. Future research to refine this intervention should focus on service users, government stakeholders and funders.
Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder.
Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms.
Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD).
Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.
Transient storage and erosion of valley fills, or sediment buffering, is a fundamental but poorly quantified process that may significantly bias fluvial sediment budgets and marine archives used for paleoclimatic and tectonic reconstructions. Prolific sediment buffering is now recognized to occur within the mountainous upper Indus River headwaters and is quantified here for the first time using optically stimulated luminescence dating, petrography, detrital zircon U-Pb geochronology, and morphometric analysis to define the timing, provenance, and volumes of prominent valley fills. This study finds that climatically modulated sediment buffering occurs over 103–104 yr time scales and results in biases in sediment compositions and volumes. Increased sediment storage coincides with strong phases of summer monsoon and winter westerlies precipitation over the late Pleistocene (32–25 ka) and mid-Holocene (~8–6 ka), followed by incision and erosion with monsoon weakening. Glacial erosion and periglacial frost-cracking drive sediment production, and monsoonal precipitation mediates sediment evacuation, in contrast to the arid Transhimalaya and monsoonal frontal Himalaya. Plateau interior basins, although volumetrically large, lack transport capacity and are consequently isolated from the modern Indus River drainage. Marginal plateau catchments that both efficiently produce and evacuate sediment may regulate the overall compositions and volumes of exported sediment from the Himalayan rain shadow.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
Objectives: This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder. Methods: Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age. Results: As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups. Conclusions: Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017, 23, 529–538)
In late 2011 the New Zealand Ministry for Primary Industries reported an increase in confirmed laboratory diagnoses of salmonellosis in dairy herds. To identify risk factors for herd-level outbreaks of salmonellosis we conducted a case-control study of New Zealand dairy herds in 2011–2012. In a multivariable analysis, use of continuous feed troughs [adjusted odds ratio (aOR) 6·2, 95% confidence interval (CI) 2·0–20], use of pelletized magnesium supplements (aOR 10, 95% CI 3·3–33) and use of palm kernel meal as a supplementary feed (aOR 8·7, 95% CI 2·5–30) were positively associated with a herd-level outbreak of salmonellosis between 1 July 2011 and 31 January 2012. We conclude that supplementary feeds used on dairy farms (regardless of type) need to be stored and handled appropriately to reduce the likelihood of bacterial contamination, particularly from birds and rodents. Magnesium supplementation in the pelletized form played a role in triggering outbreaks of acute salmonellosis in New Zealand dairy herds in 2011–2012.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
The notion of creating artificial vision using visual prostheses has been
well represented though science fiction literature and films. When we think
of retinal prostheses, we immediately think of fictional characters like The
Terminator scanning across a bar to assess patrons for appropriately fitting
clothing, or Star Trek’s Geordi La Forge with his VISOR, a visual
instrument and sensory organ replacement placed across his eyes and attached
into his temples to provide him with vision. Such devices are no longer
farfetched. In the past 20 years, significant research has been undertaken
across the globe in the race for a “Bionic Eye”. Advances in
Bionic Eye research have come from improvements in the design and
fabrication of multielectrode arrays (MEAs) for medical applications. MEAs
are already commonplace in medicine with use in applications such as the
cochlear device, cardiac pacemakers, and deep brain stimulators where
interfacing with neuronal cell populations is required.
The use of MEAs for vision prostheses is currently of significant interest.
For the most part, retinal prostheses have dominated the research landscape
owing to the ease of access and direct contact to the retinal ganglion nerve
cells. However, MEAs are also in use for direct stimulation into the optic
nerve . Retinal prostheses bypass the damaged photoreceptor cells within
the retina and instead replace the degenerate retina with electrical
stimulation to the nerve cells. Using electrical stimulation, stimulated
retinal ganglion cells have been shown to elicit a percept in the form of a
phosphene in blind patients [2–6]. Accordingly, the two diseases
commonly linked to the justification for Bionic Eye research are age-related
macular degeneration (AMD) and retinitis pigmentosa (RP), diseases which
lead to progressive loss of photoreceptor cells and diseases where the
patient has had previous vision and thus exhibits prior visual-brain
pathways. At present, there has been no reliable cure for any of the retinal
diseases that target the photoreceptor cells, and thus the development of
prosthetic devices is a viable clinical treatment option [7–9].
This is a study of the growth and decline of cities for the purpose of identifying those events in which they significantly increased in size. Significant changes in the scale of cities are important for understanding the long-term trend toward more complex and hierarchical human societies. We report the results of an inventory of cycles, upsweeps, and collapses of settlements in five separate interpolity systems. Upsweeps are instances in which the largest settlement in a world system significantly increases in size. Collapses occur when the size of the largest settlement greatly decreases and stays down for a significant period of time rather than rebounding. We use regional interpolity systems (world systems) rather than single polities or settlements as our unit of analysis. Because the accurate designation of sweeps requires interval scale measures, we are limited to those regions and time periods for which quantitative estimates of largest settlement sizes are regularly available. We find a total of 18 upsweeps and five downsweeps, and only two instances of prolonged systemwide settlement collapse. We also investigate whether or not the rate of cycles has increased over the long run, and we find that cycles of city growth and decline have not accelerated. We also find a greater rate of urban cycles in the Western (Central) System than in the East Asian System, which supports the usual notion that the Western city system was less stable than the Eastern city system.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
An Appeal to Honour and Justice, tho' it be of his Worst Enemies.
By Daniel De Foe. Being a True Account of his
Conduct in Publick Affairs.
Jerem. xviii. 18. Come and let us smite him with the Tongue,
and let us not give heed to any of his Words.
London: Printed for J. Baker, at the Black Boy in Pater-Noster-Row. 1715.
An APPEAL to Honour and Justice, &c.
I Hope the Time is come at last, when the Voice of moderate Principles may be heard; hitherto the Noise has been so great, and the Prejudices and Passions of Men so strong, that it had been but in vain to offer at any Argument, or for any Man to talk of giving a Reason for his Actions: And this alone has been the Cause why, when other Men, who, I think, have less to say in their own Defence, are appealing to the Publick, and struggling to defend themselves, I alone have been silent under the infinite Clamours and Reproaches, causeless Curses, unusual Threatnings, and the most unjust and injurious Treatment in the World.
I hear much of Peoples calling out to punish the Guilty; but very few are concern'd to clear the Innocent.