Detecting depression using an ensemble classifier based on Quality of Life scales.

Major depressive disorder (MDD) is an issue that affects 350 million people worldwide. Traditional approaches have been to identify depressive symptoms in datasets, but recently, research is beginning to explore the association between psychosocial factors such as those on the quality of life scale and mental well-being, which will lead to earlier diagnosis and prediction of MDD. In this research, an ensemble binary classifier is proposed to analyse health survey data against ground truth from the SF-20 Quality of Life scales. The classifier aims to improve the performance of machine learning techniques on large datasets and identify depressed cases based on associations between items on the QoL scale and mental illness by increasing predictive performance. On the experimental evaluation on the National Health and Nutrition Examination Survey (NHANES), the classifier demonstrated an F1 score of 0.976 in the prediction, without any incorrectly identified depression instances. Only about 4% of instances had been mistakenly classified into depressed cases, with a significant accuracy of 95.4% comparing to the result from PHQ-9 mental screen inventory. The presented ensemble binary classifier performed comparably better than each baseline algorithm in all measures and all experiments. We trained the ensemble model on the processed NHANES dataset, tested and evaluated the results of its performance against mental screen inventory and discussed the comparable predictions. Finally, we provided future research directions.

The CAF-1 complex couples Hippo pathway target gene expression and DNA replication.

The Hippo signaling pathway regulates tissue growth and organ development in many animals, including humans. Pathway activity leads to inactivation of Yorkie (Yki), a transcriptional coactivator that drives expression of growth-promoting genes. In addition, Yki has been shown to recruit chromatin modifiers that enhance chromatin accessibility and thereby enhance Yki function. Here, we asked whether changes in chromatin accessibility that occur during DNA replication could also affect Yki function. We found that depletion of the chromatin assembly complex-1 (CAF-1) complex, a histone chaperone that is required for nucleosome assembly after DNA replication, in the wing imaginal epithelium leads to increased Hippo pathway target gene expression but does not affect expression of other genes. Yki shows greater association with target sites when CAF-1 is depleted and misregulation of target gene expression is Yki-dependent, suggesting that nucleosome assembly competes with Yki for pathway targets post-DNA replication. Consistent with this idea, increased target gene expression is DNA replication dependent and newly replicated chromatin at target sites shows marked nucleosome depletion when CAF-1 function is reduced. These observations suggest a connection between cell cycle progression and Hippo pathway target expression, providing insights into functions of the Hippo pathway in normal and abnormal tissue growth.

Chronic Distal Sensory Polyneuropathy Is a Major Contributor to Balance Disturbances in Persons Living With HIV.

BACKGROUND: Medical comorbidities accumulate in older persons living with HIV (PLWH), causing disability and reduced quality of life. Sensory neuropathy and polypharmacy may contribute to balance difficulties and falls. The contribution of neuropathy is understudied. OBJECTIVE: To evaluate the contribution of chronic distal sensory polyneuropathy (cDSPN) to balance disturbances among PLWH. METHODS: Ambulatory PLWH and HIV- adults (N = 3379) were prospectively studied. All participants underwent a neurologic examination to document objective abnormality diagnostic of cDSPN and reported neuropathy symptoms including pain, paresthesias, and numbness. Participants provided detailed information regarding balance disturbance and falls over the previous 10 years. Balance disturbances were coded as minimal or none and mild-to-moderate. Covariates included age, HIV disease, and treatment characteristics and medications (sedatives, opioids, and antihypertensives). RESULTS: Eleven percent of participants reported balance disturbances at some time during the last 10 years; the rate in PLWH participants exceeding that for HIV- [odds ratio 2.59, 95% confidence interval: 1.85 to 3.64]. Fifty-two percent met criteria for cDSPN. Balance problems were more common in those with cDSPN [odds ratio = 3.3 (2.6-4.3)]. Adjusting for relevant covariates, balance disturbances attributable to cDSPN were more frequent among HIV+ than HIV- (interaction P = 0.001). Among individuals with cDSPN, older participants were much more likely to report balance disturbances than younger ones. CONCLUSIONS: cDSPN contributes to balance problems in PLWH. Assessments of cDSPN in older PLWH should be a clinical priority to identify those at risk and to aid in fall prevention and the ensuing consequences, including bone fractures, subdural hematoma, hospital admissions, and fatal injury.

Interaction analysis data of simulation gaming events using the serious game Aqua Republica.

The data presented in this article is related to the research article entitled 'Serious games as a catalyst for boundary crossing, collaboration and knowledge co-creation in a watershed governance context' (Jean et al., In press) [1]. Understanding the team dynamics related to serious game simulations is critical for understanding the potential uses and functions of these simulations for knowledge co-creation (Medema et al., 2016) [2]. The data was obtained from four independent serious game simulation events and consists of n = 40 participants. Participants were divided into small teams and were then recorded playing the serious game Aqua Republica (http://aquarepublica.com/). Interactions were tallied and interaction maps created using the visualization software GEPHI (https://gephi.org/). The interaction maps allow for a visual representation of the progression of interactions over the course of four subsequent phases of gameplay (Jordan and Henderson, 1995) [3].

Serious games as a catalyst for boundary crossing, collaboration and knowledge co-creation in a watershed governance context.

Novel methods for enhancing collaboration and interactions are required to ensure that stakeholders and governments are able to develop a shared vision that supports sustainable watershed governance. Particular attention must be placed on integrating stakeholders who would otherwise have limited decision-making power. By crossing professional, ideological and jurisdictional boundaries, stakeholders' perspectives are more likely to change than when staying within those boundaries. This process, known as boundary crossing, requires boundary objects; either artifacts, people, or institutions that play a bridging role between different boundary spaces. For this study, serious games powered by scientific models are identified as potentially effective boundary objects. A serious game simulation called Aqua Republica was used to organize game simulation events allowing stakeholders to connect in an in-person, informal and novel setting. This exploratory research aims to study the role and impact of serious games as boundary objects to enhancing collaboration and knowledge co-creation. The following research questions are addressed: (1) Do interactions increase over the course of a game simulation event? (2) Does the quality of interactions change over the course of a game simulation event? (3) Are the quantity and quality of interactions affected by pre-existing relationships? And if so, how? (4) How does the relationship between participants change over the course of a game simulation event? As part of this study, four game simulation events were organized that included students, professionals and diverse stakeholder groups working in watershed management contexts across Eastern Canada with 40 participants in total. Participants were divided into teams of 3-5 members and were surveyed and their interactions recorded. An interaction and social network analysis of the audiovisual recordings of each game simulation event indicates that interactions between participants increase in both quantity and quality as the game progresses. The analysis shows that serious game simulations provide an intervention platform not only to facilitate cross-boundary interactions, but also to strengthen relationships between diverse stakeholders, as expressed by an increase in mutual trust and empathy, as well as an improved understanding among the participants of the watershed system and the complex issues at stake.

A comprehensive land-use/hydrological modeling system for scenario simulations in the Elbow River watershed, Alberta, Canada.

The Elbow River watershed in Alberta covers an area of 1,238 km(2) and represents an important source of water for irrigation and municipal use. In addition to being located within the driest area of southern Canada, it is also subjected to considerable pressure for land development due to the rapid population growth in the City of Calgary. In this study, a comprehensive modeling system was developed to investigate the impact of past and future land-use changes on hydrological processes considering the complex surface-groundwater interactions existing in the watershed. Specifically, a spatially explicit land-use change model was coupled with MIKE SHE/MIKE 11, a distributed physically based catchment and channel flow model. Following a rigorous sensitivity analysis along with the calibration and validation of these models, four land-use change scenarios were simulated from 2010 to 2031: business as usual (BAU), new development concentrated within the Rocky View County (RV-LUC) and in Bragg Creek (BC-LUC), respectively, and development based on projected population growth (P-LUC). The simulation results reveal that the rapid urbanization and deforestation create an increase in overland flow, and a decrease in evapotranspiration (ET), baseflow, and infiltration mainly in the east sub-catchment of the watershed. The land-use scenarios affect the hydrology of the watershed differently. This study is the most comprehensive investigation of its nature done so far in the Elbow River watershed. The results obtained are in accordance with similar studies conducted in Canadian contexts. The proposed modeling system represents a unique and flexible framework for investigating a variety of water related sustainability issues.

Anomalous left main coronary artery causing a myocardial infarction in a 14-year-old boy.

A 14-year-old boy presented with exertional chest pain and was found to have rising cardiac biomarkers. The electrocardiogram revealed ST-segment elevation and T-wave inversion in the anterolateral leads. Coronary arteriograms and coronary computed tomography (CCT) showed an anomalous left main coronary artery originating from the right coronary sinus of Valsalva and coursing intramurally within the wall of the aorta between the aorta and the pulmonary trunk. The proximal left main was narrow with normal distal left main, left anterior descending, and left circumflex coronary arteries. The patient underwent surgical de-roofing of the intramural course of the left main artery with relief of his symptoms. Coronary artery anomalies have been found in 1.3% of the patients in a large arteriographic study. These anomalies are classified on the basis of the origin of the coronary arteries, as well as their course and distribution. Many of these variations are discovered incidentally at arteriography or autopsy. However, some of the anomalies cause symptoms, and a few of them can cause sudden cardiac death, even at a young age.

Incidence of post-dural puncture headache in research volunteers.

OBJECTIVE: To determine the frequency and risk factors of post-dural puncture headache (PDPH) in research volunteers. BACKGROUND: Despite increasing interest in measuring cerebrospinal fluid (CSF) biomarkers to investigate disease pathogenesis and diagnosis, previous case series have evaluated lumbar puncture (LP) safety only in clinical care. PDPH is a common complication after LP. METHODS: We determined the frequency of PDPH in neurologically unselected HIV seropositive and seronegative adults volunteering for research, as well as the variables associated with the development of PDPH. Variables studied were body mass index (BMI), HIV serostatus, volume of CSF removed, number of previous LPs, use of pre-medication, LP position, lumbar space, number of needle passes, whether or not aspiration was used, CSF white blood cell counts, CSF red blood cell counts, CD4 count, CD4 nadir, CSF HIV viral load, plasma HIV viral load, and race. RESULTS: Of 675 LPs performed over 1 year, headache developed in 38 (5.6%; 95% CI 4.2, 7.1). Most PDPH (92%) resolved spontaneously or with conservative medical management; 3 required epidural blood patch. Greater headache risk was associated with lower BMI (BMI ≤25 vs >25) (OR 3.3; CI 95% 1.5, 7.0; P = .001) and less prior LP experience (previous LPs ≤2 vs >2) (OR 2.1; CI 95% 1.1, 4.1; P = .03). PDPH was not significantly (P > .05) related to HIV serostatus, CSF volume, or gender. CONCLUSION: In this study, where tolerance to risk was low because LPs were done for research rather than clinical purposes and healthy controls were included, adverse effects were mild and self-limited.

Catecholamine-o-methyltransferase polymorphisms are associated with postoperative pain intensity.

OBJECTIVES: single nucleotide polymorphisms (SNPs) in the genes for catecholamine-O-methyltransferase (COMT), µ-opioid receptor and GTP cyclohydrolase (GCH1) have been linked to acute and chronic pain states. COMT polymorphisms are associated with experimental pain sensitivity and a chronic pain state. No such association has been identified perioperatively. We carried out a prospective observational clinical trial to examine associations between these parameters and the development of postoperative pain in patients undergoing third molar (M3) extraction. METHODS: psychologic and clinical parameters were measured prospectively in a single homogeneous cohort of 100 patients undergoing M3 extraction. We genotyped the patients for SNPs within GCH1, COMT, and µ-opioid receptor 1. Primary outcome was the occurrence of pain, 3 months after surgery. Other outcomes included pain measures in the early postoperative period and the week after surgery. RESULTS: seven patients (7/98; 7.1%) had persistent pain. Patients with and without persistent pain were similar in terms of perioperative demographic, psychological, and clinical parameters. The proportion who reported adequate postoperative analgesia was greater amongst those with the GG genotype for either rs4818 or rs6269 than those without (P<0.0001). The rare forms of COMT SNPs rs4818 and rs6269 were associated with postoperative pain of lesser intensity at rest (P=0.02, 0.03 respectively) and on movement (P=0.02, 0.01, respectively). The number of days until analgesia was not required during the first postoperative week was associated with GCH1 SNPs (rs8007267, P=0.05; rs3783641, P=0.01; rs10483636, P=0.002). DISCUSSION: we report an early demonstration of a COMT SNP association with a clinically meaningful pain outcome after elective surgery.

An alkynylboronate cycloaddition strategy to functionalised benzyne derivatives.

A new approach to benzyne precursors has been developed that involves the [4+2] cycloaddition of trimethylsilyl alkynylboronates with 2-pyrones, followed by oxidation and trifluoromethylsulfonylation of the boronate moiety.

Cardiac computed tomography, changing the way we look at the heart.

Cardiac computed tomography angiography (CCTA) produces excellent anatomic information of the coronary arteries and other cardiac structures. A high negative predictive value (99%) for the exclusion of coronary lesions establishes CCTA as a highly effective noninvasive alternative to invasive coronary angiography. It is, however, less accurate for determining degrees of lesion severity, and intermediate grade lesions require either physiologic stress testing or invasive coronary angiography. CCTA allows visualization of the vessel wall so plaque can be classified as soft, calcified, or mixed on the basis of Hounsfield units. Precise quantification of the plaque burden is readily performed with coronary artery calcium scoring (CACS). This measurement of plaque burden is one of the most predictive of future cardiac events and mortality available. CCTA also serves as an excellent tool prior to surgical and percutaneous cardiac procedures. CT scanning continues to evolve as an imaging modality for all stages of the treatment of cardiac disease: CACS for risk assessment for asymptomatic patients, CCTA to evaluate patients with symptoms, and cardiac CT to plan cardiac procedures.

Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy.

OBJECTIVE: Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long-term use in highly active ARV therapy. METHODS: We evaluated current and past exposure to PIs as a risk factor for DSPN in 1,159 HIV-infected individuals enrolled in a large, prospective, observational, multicenter study. Signs of DSPN were ascertained by neurological examination. Subjects were grouped into categories according to past and current exposure to any ARV and to PIs. We included disease indicators such as nadir CD4, plasma viral load, and duration of HIV infection, as well as advancing age and exposure to dideoxynucleoside ARVs in multivariate models. RESULTS: In univariate analyses, both past and current PI exposure significantly increased the risk for DSPN. However, after adjusting for previously validated concomitant risk factors in multivariate models, none of the PI exposure groups was more likely to have DSPN than ARV naive subjects. A secondary evaluation of duration of PI use and exposure to individual PI drugs was similarly nonsignificant in multivariate models, except for small effects of amprenavir and lopinavir. INTERPRETATION: Evaluation of concomitant risks for HIV DSPN suggests that the independent risk attributable to PIs, if any, is small. This risk must be weighed against the important role of PIs in modern ARV therapy regimens.

A [4 + 2] cycloaddition strategy to pyridine boronic ester derivatives.

Alkynylboronate cycloadditions of 1,4-oxazin-2-ones and 2-pyrazinones provide a direct and regioselective route to functionalized pyridine boronic ester derivatives.

An alkynylboronic ester cycloaddition route to functionalised aromatic boronic esters.

A series of functionalised aromatic boronic esters have been prepared via the regioselective cycloaddition of 2-pyrones with alkynylboronates.

Antioxidant strategies for Alzheimer's disease.

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from beta-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E and Ginkgo biloba extract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, beta-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.