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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Drawing on Roman Catholic and ecumenical expertise, this article takes an honest look at the experiences and hopes of those abused. Many in the churches assume that victims seek financial compensation or legal redress. However, research indicates that many victims primarily seek truth and justice as a means of closure and that their struggles with church leadership arise when truth and justice are repeatedly withheld. This makes forgiveness near-impossible and often results in the victim being re-traumatized by the systemic re-abuse they experience. Ultimately, there is no substitute for full and genuine meeting with victims, which requires the church to lay aside its power and authority and engage with humility and proper deference to the victims abused at the hands of the church. Without such openness, the victims cannot move on, and neither can the churches.
Item response theory (IRT) model applications extend well beyond cognitive ability testing, and various patient-reported outcomes (PRO) measures are among the more prominent examples. PRO (and like) constructs differ from cognitive ability constructs in many ways, and these differences have model fitting implications. With a few notable exceptions, however, most IRT applications to PRO constructs rely on traditional IRT models, such as the graded response model. We review some notable differences between cognitive and PRO constructs and how these differences can present challenges for traditional IRT model applications. We then apply two models (the traditional graded response model and an alternative log-logistic model) to depression measure data drawn from the Patient-Reported Outcomes Measurement Information System project. We do not claim that one model is “a better fit” or more “valid” than the other; rather, we show that the log-logistic model may be more consistent with the construct of depression as a unipolar phenomenon. Clearly, the graded response and log-logistic models can lead to different conclusions about the psychometrics of an instrument and the scaling of individual differences. We underscore, too, that, in general, explorations of which model may be more appropriate cannot be decided only by fit index comparisons; these decisions may require the integration of psychometrics with theory and research findings on the construct of interest.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
We aim to examine the prescription patterns of local psychiatrists for adolescent patients with depressive disorder, treated on an outpatient basis, as part of an integrated programme for management of mood disorders in adolescent patients (IPMDA) in Singapore.
Methods
An longitudinal cohort observational study was carried out at a psychiatry out-patient department in the National University Hospital of Singapore, as part of a specialised programme for the treatment of adolescents, aged 13 to 18, with depressive disorder. The data which were collected included information about age, gender, education, therapy provision and drug prescription included generic name and dosing.
Results
A total of 129 patients were included in the study. 81.7% (n = 105) were females and 18.3% (n = 24) were males. 72 (76.4% female, 23.6% male) patients were started on medications. All patients were initiated on a monotherapy regime of antidepressants.
The most commonly prescribed antidepressant was Fluoxetine (58.3%), followed by Sertraline (18.1%), Fluvoxamine (12.5%), Escitalopram (6.9%), Mirtazapine (2.8%) and Amitriptyline (1.4%).
Conclusion
Our findings revealed that current psychopharmacology practice for depressive disorder in Singapore generally follows the published Singaporean treatment guidelines, which is generally kept up to date with wider international recommendations.
The factor of pricing may affect the lower prescription of certain medications, such as Escitalopram, as it is more expensive than the other prescribed medications in the list.
Carbonated soft-drink consumption is detrimental to multiple facets of adolescent health. However, little is known about temporal trends in carbonated soft-drink consumption among adolescents, particularly in non-Western countries. Therefore, we aimed to examine this trend in representative samples of school-going adolescents from eighteen countries in Africa, Asia and the Americas. Cross-sectional data from the Global School-based Student Health Survey 2009–2017 were analysed. Carbonated soft-drink consumption referred to drinking carbonated soft-drinks at least once per day in the past 30 d. The prevalence of carbonated soft-drink consumption was calculated for each survey, and crude linear trends were assessed by linear regression models. Data on 74 055 students aged 12–15 years were analysed (mean age 13·9 (sd 1·0) years; 49·2 % boys). The overall mean prevalence of carbonated soft-drink consumption was 42·1 %. Of the eighteen countries included in the study, significant decreasing, increasing and stable trends of carbonated soft-drink consumption were observed in seven, two and nine countries, respectively. The most drastic decrease was observed in Kuwait between 2011 (74·4 %) and 2015 (51·7 %). Even in countries with significant decreasing trends, the decrease was rather modest, while some countries with stable trends had very high prevalence across time (e.g. Suriname 80·5 % in 2009 and 79·4 % in 2016). The prevalence of carbonated soft-drink consumption was high in all countries included in the present analysis, despite decreasing trends being observed in some. Public health initiatives to reduce the consumption of carbonated soft-drink consumption among adolescents are urgently required.
Emotion is vital part of our routine communication. The facial feedback hypothesis is the theory of how internal emotion is modulated by the external facial movements used to express it. Botulinum toxin injection is the most common aesthetic procedure in the United States. It has been studied extensively for its cosmetic use in wrinkle reduction, but its secondary psychological effects have only been elucidated gradually over the last two decades. Although neurotoxin is considered safe and effective, it may also potentially affect our facial expressions and communications. Similar to neurotoxin, another example that affects our social interactions is the facial mask, after the COVID-19 pandemic. In this chapter, we hereby discuss how neurotoxin affects our emotions and nonverbal communications.
This study investigates the effect of structural damping on vortex-induced vibration (VIV) of a circular cylinder when the mass ratio is below its critical value. It is confirmed by water-channel experiments and a reduced-order model (ROM) that the previously identified phenomenon of VIV forever, i.e. resonance oscillations at any reduced velocity, persists even with high structural damping. Of interest, the ROM results reveal that the wake mode for VIV forever is unstable with a constant positive growth rate with increasing reduced velocity, while the experimental results suggest that VIV forever is associated with a synchronisation between the non-stationary cylinder vibration frequency and the vortex-shedding frequency.
Optimal preoperative therapy regimen in the treatment of resectable retroperitoneal sarcoma (RPS) remains unclear. This study compares the impact of preoperative radiation, chemoradiation and chemotherapy on overall survival (OS) in RPS patients.
Materials and Methods:
The National Cancer Database (NCDB) was queried for patients with non-metastatic, resectable RPS (2006–15). The primary endpoint was OS, evaluated by Kaplan–Meier method, log-rank test, Cox multivariable analysis and propensity score matching.
Results:
A total of 1,253 patients met the inclusion criteria, with 210 patients (17%) receiving chemoradiation, 850 patients (68%) receiving radiation and 193 patients (15%) receiving chemotherapy. On Cox multivariable analysis, when compared to preoperative chemoradiation, preoperative radiation was not associated with improved OS (hazards ratio [HR] 0·98, 95% CI 0·76–1·25, p = 0·84), while preoperative chemotherapy was associated with worse OS (HR 1·64, 95% CI 1·24–2·18, p < 0·001). Similar findings were observed in 199 and 128 matched pairs for preoperative radiation and chemotherapy, respectively, when compared to preoperative chemoradiation.
Findings:
Our study suggested an OS benefit in using preoperative chemoradiation compared to chemotherapy alone, but OS outcomes were comparable between preoperative chemoradiation and radiation alone.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients.
Methods and results:
Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012–2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61–264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R2 = 0.615).
Conclusions:
N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function.
Over the past decade in the Netherlands, most operators have only developed a single doublet. The learning effect from these single events is suboptimal, and operators have only been capable of developing doublets in areas with relatively low exploration risk. This ‘stand-alone’ approach can be significantly improved by a collective approach to derisk regions with similar subsurface characteristics. Such a play-based portfolio approach, which is common in the oil and gas industry, can help to accelerate the development of the geothermal industry through unlocking resource potential in areas marked by high upfront geological risk, effectively helping reduce costs for the development. The basis of the methodology is to deploy new information to the play portfolio by trading off with the risk of the first wells, resulting in a strong geological risk reduction.
The added value of the portfolio approach is demonstrated for the Netherlands in this paper through a comparison with a ‘stand-alone’ development. In the stand-alone approach, each new project will be equally risky, and therefore relatively unprofitable. In the case of a portfolio approach, all experience about the play is used optimally for derisking. In case of success, subsequent projects will have a higher chance of being successful, due to the experience gained in previous projects. Even if a project fails, this may help in increasing the probability of success for subsequent projects. For plays that are initially considered too risky for the market to start developing, the value of information (VoI) of a play-based portfolio approach will help by derisking the play to such an extent that it becomes attractive for the market to develop, even at high initial risk. It can be demonstrated for several geothermal plays in the Netherlands that by adopting the portfolio approach, the probability of a play being developed becomes higher, the number of successfully developed projects increases and the average profitability of the project will also be higher. Five more advantages are: (1) continuous improvement by integrated project development, (2) cost reduction through synergy, efficiency and standardisation, (3) optimisation of the surface heat demand and infrastructure, (4) the possibility of structural research and development (R&D) and innovation, and (5) financing advantages. The advantages reinforce each other.
A preliminary estimate of the geothermal potential of the Netherlands adopting the portfolio approach is between 90 and 275 Petajoules (PJ). For about 350 doublets being developed, producing about 70 PJ, the value of the advantage of the play-based portfolio approach is €2 billion for the three main plays: Rotliegend, Triassic and Jurassic/Cretaceous. The learning effects of synergy, efficiency and standardisation are expected to be significant.
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 (
${\sim}60\%$
), 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.
We examined whether intensive home treatment (IHTT) was beneficial for acute schizophrenia, using the Clinical Global Impression (CGI) scale as a measure of severity and change, between 2011–2015. Demographic and clinical details were collected.
Results
309 cases were referred to IHTT, comprising 245 separate individuals. This represented all severe acute psychotic episodes in Edinburgh during the study period. Three quarters of individuals had an improvement in CGI following IHTT and were safely managed at home. Thirty-nine per cent of all people received three or more regular medications. Comorbid drug and alcohol misuse was also frequently seen.
Clinical implications
IHTT can be beneficial to those suffering an acute episode of psychosis and has been shown to improve overall clinical outcome based on the CGI. Medication polypharmacy, as well as drug and alcohol use, are commonly seen in this population.
Declaration of interest
M.T. worked in IHTT at the time of the study, and has received fees and/or hospitality from Janssen, Lundbeck and Otsuka in the past 3 years.
Zwaan et al. integrated previous articles to promote making replications mainstream. We wholeheartedly agree. We extend their discussion by highlighting several existing initiatives – the Replication Recipe and the Collaborative Education and Research Project (CREP) - which aim to make replications mainstream. We hope this exchange further stimulates making replications mainstream.
Pompe disease is a lysosomal storage disorder caused by a deficiency of the
enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory
weakness with or without cardiomyopathy. The objective of our review was to
systematically evaluate the quality of evidence from the literature to
formulate evidence-based guidelines for the diagnosis and management of
patients with Pompe disease. The literature review was conducted using
published literature, clinical trials, cohort studies and systematic
reviews. Cardinal treatment decisions produced seven management guidelines
and were assigned a GRADE classification based on the quality of evidence in
the published literature. In addition, six recommendations were made based
on best clinical practices but with insufficient data to form a guideline.
Studying outcomes in rare diseases is challenging due to the small number of
patients, but this is in particular the reason why we believe that informed
treatment decisions need to consider the quality of the evidence.