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Individuals with bipolar disorder (BD) are differentially affected by insulin resistance. Individuals without history of mental disorder with insulin resistance usually have high peripheral concentrations of phenylalanine (PHE) and tyrosine (TYR) together. Catecholamine dysfunction is described to be a state-dependend phenomen in patients suffering from BD. Catecholamines are synthesized from essential amino acids PHE and TYR which are biotransformed to dopamine and subsequently converted to nor/adrenaline. Amino acid dysregulation may be a possible mediator of insulin resistance in BD.
Peripheral PHE and TYR concentrations were investigated in euthymic adults with BD. Amino acid differences between normal and overweight individuals with BD were evaluated and outcomes were correlated with the measures of glucose homeostasis.
Mean plasma PHE to TYR ratio (PHE/TYR) was at the upper limit of the normal range in the whole sample. Enrolled subjects with PHE/TYR beyond the limits of normal exhibited the highest number of prior affective episodes. Sex-specific differences were noted as overweight BD females showed different profiles than normal-weight women. In the overweight females, PHE and TYR concentrations were significantly higher compared to normal-weight women. Significant correlations were noticed between PHE, TYR and PHE/TYR with insulin/Homeostasis Model of Assessment (HOMA)-IR in the whole sample and the subgroup of BD women.
These significant differences in gender, amino acid pathways and in correlations with immune marker as well as insulin function have not been reported previously. Taken together, increased levels of PHE in BD should be considered when adjudicating diabetes risk especially in women.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Patients with bipolar disorder experience a wide range of depressive and manic symptoms. Only 2 drugs are FDA-approved to treat episodes of both mania and depression in patients with bipolar disorder, highlighting the need for treatments with proven efficacy at opposite poles of the bipolar spectrum. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, is approved in the US for the treatment of both bipolar depression and manic and mixed episodes associated with bipolar I disorder. Cariprazine has previously demonstrated broad efficacy in patients with bipolar mania, with significantly greater improvement in favor of cariprazine vs placebo (PBO) across all individual symptom domains (P<.001) measured by the Young Mania Rating Scale (YMRS). Additionally, cariprazine has demonstrated efficacy vs PBO in 3 phase II/III clinical studies in patients with depressive episodes associated with bipolar I disorder (NCT01396447, NCT02670538, NCT02670551). To further assess the broad efficacy of cariprazine in patients with bipolar I disorder, we performed post hoc analyses to evaluate the range of depressive symptoms comprising the individual items of the Montgomery-Åsberg Depression Rating Scale (MADRS) in patients from the bipolar depression studies.
Data from the 3 randomized, double-blind, PBO-controlled trials in patients with bipolar depression were pooled. Least squares (LS) mean change from baseline to week 6 in MADRS individual items was assessed in the pooled cariprazine 1.5 and 3 mg/d groups vs PBO using a mixed-effects model for repeated measures in the intent-to-treat (ITT) population.
There were 1383 patients in the ITT population (placebo=460; cariprazine 1.5-3 mg/d=923). At week 6, LS mean change from baseline was significantly greater for cariprazine 1.5-3 mg/d vs PBO on 9 of 10 individual MADRS items: Apparent Sadness (-2.0 vs -1.6, P<.0001); Reported Sadness (-2.0 vs -1.6, P<.0001); Reduced Sleep (-1.6 vs -1.4, P=.0357); Reduced Appetite (-1.2 vs -1.0, P=.0001); Concentration Difficulties (-1.5 vs -1.2, P=.0002); Lassitude (-1.7 vs -1.4, P=.0003); Inability To Feel (-1.7 vs -1.5, P=.0009); Pessimistic Thoughts (-1.4 vs -1.2, P=.0054) and Suicidal Thoughts (-0.3 vs -0.2, P=.0383); differences between cariprazine and PBO on the Inner Tension item were not significant.
Significant improvement in most MADRS single items suggests broad efficacy in depressive symptoms for cariprazine 1.5-3 mg/d vs PBO in patients with bipolar depression. Coupled with broad efficacy in manic symptoms as demonstrated by significant improvement in all YMRS individual items in patients with bipolar mania or mixed episodes, cariprazine appears be effective across the range of symptoms that affect patients with bipolar disorder.
Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.
We describe the investigation of two temporally coincident illness clusters involving salmonella and Staphylococcus aureus in two states. Cases were defined as gastrointestinal illness following two meal events. Investigators interviewed ill persons. Stool, food and environmental samples underwent pathogen testing. Alabama: Eighty cases were identified. Median time from meal to illness was 5·8 h. Salmonella Heidelberg was identified from 27 of 28 stool specimens tested, and coagulase-positive S. aureus was isolated from three of 16 ill persons. Environmental investigation indicated that food handling deficiencies occurred. Colorado: Seven cases were identified. Median time from meal to illness was 4·5 h. Five persons were hospitalised, four of whom were admitted to the intensive care unit. Salmonella Heidelberg was identified in six of seven stool specimens and coagulase-positive S. aureus in three of six tested. No single food item was implicated in either outbreak. These two outbreaks were linked to infection with Salmonella Heidelberg, but additional factors, such as dual aetiology that included S. aureus or the dose of salmonella ingested may have contributed to the short incubation periods and high illness severity. The outbreaks underscore the importance of measures to prevent foodborne illness through appropriate washing, handling, preparation and storage of food.
Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.
Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four public hospitals in rural Mopani District, South Africa. Data were obtained from TB registers and patients’ clinical records. There was a 13% decrease in overall number of TB cases, which was similar for cases registered as EPTB (n = 399 in 2009 vs. 336 in 2013; P < 0·01) and for PTB (1031 vs. 896; P < 0·01). Among EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P < 0·01), TB meningitis and TB of bones increased significantly (P < 0·01 and P = 0·02, respectively) and TB pleural effusion and lymphadenopathy remained the same. This study shows a reduction of EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.
Compound-specific radiocarbon analysis (CSRA) of benzene polycarboxylic acids (BPCAs) yields molecular-level, source-specific information necessary to constrain isotopic signatures of pyrogenic carbon. However, the purification of individual BPCAs requires a multistep procedure that typically results in only microgram quantities of the target analyte(s). Such small samples are highly susceptible to contamination by extraneous carbon, which needs to be minimized and carefully accounted for in order to yield accurate results. Here, we undertook comprehensive characterization and quantification of contamination associated with molecular radiocarbon (14C) BPCA analyses through systematic processing of multiple authentic standards with both fossil and modern 14C signatures at various concentrations. Using this approach, we precisely apportion the contribution of extraneous carbon with respect to the four implemented subprocedures. Assuming a constant source and quantity of extraneous carbon we correct and statistically evaluate uncertainties in resulting 14C data. Subsequently, we examine the results of triplicate analyses of reference materials representing four different environmental matrices (sediment, soil, aerosol, riverine natural organic matter) and apportion their BPCA sources in terms of carbon residues derived from biomass or fossil fuel combustion. This comprehensive approach to CSRA facilitates retrieval of robust 14C data, with application in environmental studies of the continuum of pyrogenic carbon.
Introduction of antiretroviral therapy (ART) has dramatically reduced the incidence of infectious ocular diseases in human immunodeficiency virus (HIV)-infected individuals. However, the effects of long-term ART and chronic HIV infection on the eye are ill-defined. This study determined the occurrence and severity of ocular diseases among 342 participants in a rural South African setting: HIV-naïve (n = 105), HIV-infected ART-naïve (n = 16), HIV-infected on ART for <12 months (short-term ART; n = 56) and HIV-infected individuals on ART for >36 months (long-term ART; n = 165). More HIV-infected participants presented with an external eye condition, in particular blepharitis, than HIV-naïve individuals (18% vs. 7%; age-adjusted odds ratio (aOR) = 2·8, P < 0·05). Anterior segment conditions (particularly keratoconjunctivitis sicca and pterygium) were also more common (50% vs. 27%; aOR = 2·4; P < 0·01). Compared with individuals on short-term ART, participants receiving long-term ART were more likely to have clinically detectable cataract (57% vs. 38%; aOR = 2·2, P = 0·01) and posterior segment diseases, especially HIV retinopathy (30% vs. 11%; aOR = 3·4, P < 0·05). Finally, long-term ART was significantly associated with presence of HIV retinopathy (P < 0·01). These data implicate that ocular disease is more common and of more diverse etiology among HIV-infected individuals, especially those on long-term ART and suggest that regular ophthalmological monitoring of HIV-infected individuals on ART is warranted.
Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.
The study of foraging success in marine predators is complicated by a lack of direct observations and relies mostly on proxy measures of foraging success. This study assessed spatial and temporal patterns of changes in body condition of southern elephant seals (Mirounga leonina) from Marion Island, based on changes in drift rates (which are related to gains and losses of blubber). Seals showed substantial individual variation in condition changes throughout migrations, which was not explained by age-, sex- or reproductive stages. Substantial variation was also evident in the spatial patterns of condition changes, although an area south of the Antarctic Polar Front (APF) between 10°E and 35°E was evidently associated with moderate, yet consistent gains in condition. Seals that foraged more distantly from Marion Island displayed more extreme gains and losses in condition, suggesting a possible risk/reward trade-off associated with foraging further afield versus closer to the island. Increased condition was consistently negatively related to sea surface temperature, suggesting that seals were generally improving their condition faster in cooler water masses. These results support previous studies predicting that continued warming of the Southern Ocean will result in changes to the habitat use patterns exhibited by southern elephant seals at sea.
It is paramount to understand the epidemiology of chronic hepatitis B to inform national policies on vaccination and screening/testing as well as cost-effectiveness studies. However, information on the national (Scottish) prevalence of chronic hepatitis B by ethnic group is lacking. To estimate the number of people with chronic hepatitis B in Scotland in 2009 by ethnicity, gender and age, the test data from virology laboratories in the four largest cities in Scotland were combined with estimates of the ethnic distribution of the Scottish population. Ethnicity in both the test data and the Scottish population was derived using a name-based ethnicity classification software (OnoMAP; Publicprofiler Ltd, UK). For 2009, we estimated 8720 [95% confidence interval (CI) 7490–10 230] people aged ⩾15 years were living with chronic hepatitis B infection in Scotland. This corresponds to 0·2% (95% CI 0·17–0·24) of the Scottish population aged ⩾15 years. Although East and South Asians make up a small proportion of the Scottish population, they make up 44% of the infected population. In addition, 75% of those infected were aged 15–44 years with almost 60% male. This study quantifies for the first time on a national level the burden of chronic hepatitis B infection by ethnicity, gender and age. It confirms the importance of promoting and targeting ethnic minority groups for hepatitis B testing.
We demonstrate that alternating the oxygen partial pressure gradient across a yttria-stabilized zirconia (YSZ) electrolyte membrane prior to solid oxide fuel cell (SOFC) testing with nanoporous Pt electrodes greatly increases (e.g. by >70-fold at 350 °C) peak power density compared with devices without pretreatment. Transiently altering the oxygen activity at the cathode–YSZ interface appears to change the wetting characteristics of the nanoporous Pt, significantly affecting the stability and low-temperature performance of the SOFCs. Image analysis and impedance spectroscopy results suggest that an increase in triple-phase boundary area fraction at the cathode–YSZ interface contributes to the observed effect.
Obesity is increasingly prevalent in bipolar disorder (BD) but data about the impact of elevated body mass index (BMI) on brain white-matter integrity in BD are sparse. Based on extant literature largely from structural magnetic resonance imaging (MRI) studies, we hypothesize that increased BMI is associated with decreased fractional anisotropy (FA) in the frontal, temporal, parietal and occipital brain regions early in the course of BD.
A total of 26 euthymic adults (12 normal weight and 14 overweight/obese) with remitted first-episode mania (FEM) and 28 controls (13 normal weight and 15 overweight/obese) matched for age, handedness and years of education underwent structural MRI and diffusion tensor imaging scans.
There are significant effects of diagnosis by BMI interactions observed especially in the right parietal lobe (adjusted F1,48 = 5.02, p = 0.030), occipital lobe (adjusted F1,48 = 10.30, p = 0.002) and temporal lobe (adjusted F1,48 = 7.92, p = 0.007). Specifically, decreased FA is found in the right parietal (F1,23 = 5.864, p = 0.023) and occipital lobes (F1,23 = 4.397, p = 0.047) within overweight/obese patients compared with normal-weight patients with FEM. Compared with overweight/obese controls, decreased FA is observed in right parietal (F1,25 = 6.708, p = 0.015), temporal (F1,25 = 10.751, p = 0.003) and occipital (F1,25 = 9.531, p = 0.005) regions in overweight/obese patients with FEM.
Our findings suggest that increased BMI affects temporo-parietal-occipital brain white-matter integrity in FEM. This highlights the need to further elucidate the relationship between obesity and other neural substrates (including subcortical changes) in BD which may clarify brain circuits subserving the association between obesity and clinical outcomes in BD.
Major depressive disorder (MDD) and generalized anxiety disorder (GAD) have the highest co-morbidity rates within the internalizing disorders cluster, yet no Internet-based cognitive behavioural therapy (iCBT) programme exists for their combined treatment.
We designed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression. Study 1 was a randomized controlled trial (RCT) comparing the iCBT programme (n = 46) versus wait-list control (WLC; n = 53) for patients diagnosed by structured clinical interview with MDD, GAD or co-morbid GAD/MDD. Primary outcome measures were the Patient Health Questionnaire nine-item scale (depression), Generalized Anxiety Disorder seven-item scale (generalized anxiety), Kessler 10-item Psychological Distress scale (distress) and 12-item World Health Organization Disability Assessment Schedule II (disability). The iCBT group was followed up at 3 months post-treatment. In study 2, we investigated the adherence to, and efficacy of the same programme in a primary care setting, where patients (n = 136) completed the programme under the supervision of primary care clinicians.
The RCT showed that the iCBT programme was more effective than WLC, with large within- and between-groups effect sizes found (>0.8). Adherence was also high (89%), and gains were maintained at 3-month follow-up. In study 2 in primary care, adherence to the iCBT programme was low (41%), yet effect sizes were large (>0.8). Of the non-completers, 30% experienced benefit.
Together, the results show that iCBT is effective and adherence is high in research settings, but there is a problem of adherence when translated into the ‘real world’. Future efforts need to be placed on developing improved adherence to iCBT in primary care settings.
The Parkes pulsar data archive currently provides access to 144044 data files obtained from observations carried out at the Parkes observatory since the year 1991. Around 105 files are from surveys of the sky, the remainder are observations of 775 individual pulsars and their corresponding calibration signals. Survey observations are included from the Parkes 70 cm and the Swinburne Intermediate Latitude surveys. Individual pulsar observations are included from young pulsar timing projects, the Parkes Pulsar Timing Array and from the PULSE@Parkes outreach program. The data files and access methods are compatible with Virtual Observatory protocols. This paper describes the data currently stored in the archive and presents ways in which these data can be searched and downloaded.
We describe the habitat use of 22 male southern elephant seals (Mirounga leonina) satellite tagged at Marion Island between 2004 and 2008. While a few areas of increased utilization appeared to be associated with areas of shallower bathymetry (such as sea-floor ridges and fracture zones), seals in our study did not target other areas of shallow bathymetry within close proximity to Marion Island. Rather, most elephant seals foraged pelagically over very deep water where much variation was evident in diel vertical migration strategies. These strategies resulted in generally deeper and longer dives than what has been reported for male elephant seals from other colonies. No significant differences were recorded for dive durations or dive depths between adults and sub-adults. However, younger animals displayed a positive relationship between dive durations and age, as well as between dive depths and age, while these relationships became negative for older animals. Mixed model outputs suggested that seals increased their aerobic fitness as migrations progressed, enabling them to undertake longer dives. We conclude that Marion Island male elephant seals exhibit much variability in dive strategy and are seemingly capable of exploiting a range of different prey types occurring in various depth layers.
Spin-coating is a process used to fabricate thin films for device applications. In this paper, lubrication theory is used to derive an axisymmetric model for the spin-coating of two immiscible vertically stratified Newtonian thin films. The model includes gravitational, van der Waals, capillary and viscous forces, differences in liquid layer properties and evaporation/condensation effects. Thinning calculations focus on the effects of viscosity and condensation/evaporation. In this case, for layers of uniform thickness, the lower layer thins monotonically yet never reaches zero thickness. With evaporation mass loss the upper layer disappears in finite time, whereas with condensation effects the upper layer approaches a steady-state thickness. Fully nonlinear calculations are carried out for films with non-uniform thickness and the deviation of the interfaces from the flat state is monitored. In general, disturbances to the lower layer have a greater effect on the upper layer than those of disturbances of the upper layer on the lower layer. Disturbances along the upper gas–liquid free surface propagate outward more rapidly than those along the lower liquid–liquid interface and disturbances that decrease the film thickness tend to dissipate more slowly.