Finding 2-Edge and 2-Vertex Strongly Connected Components in Quadratic Time

We present faster algorithms for computing the 2-edge and 2-vertex strongly connected components of a directed graph, which are straightforward generalizations of strongly connected components. While in undirected graphs the 2-edge and 2-vertex connected components can be found in linear time, in directed graphs only rather simple $O(m n)$-time algorithms were known. We use a hierarchical sparsification technique to obtain algorithms that run in time $O(n^2)$. For 2-edge strongly connected components our algorithm gives the first running time improvement in 20 years. Additionally we present an $O(m^2 / \log{n})$-time algorithm for 2-edge strongly connected components, and thus improve over the $O(m n)$ running time also when $m = O(n)$. Our approach extends to k-edge and k-vertex strongly connected components for any constant k with a running time of $O(n^2 \log^2 n)$ for edges and $O(n^3)$ for vertices

Scoring Protein Relationships in Functional Interaction Networks Predicted from Sequence Data

The abundance of diverse biological data from various sources constitutes a rich source of knowledge, which has the power to advance our understanding of organisms. This requires computational methods in order to integrate and exploit these data effectively and elucidate local and genome wide functional connections between protein pairs, thus enabling functional inferences for uncharacterized proteins. These biological data are primarily in the form of sequences, which determine functions, although functional properties of a protein can often be predicted from just the domains it contains. Thus, protein sequences and domains can be used to predict protein pair-wise functional relationships, and thus contribute to the function prediction process of uncharacterized proteins in order to ensure that knowledge is gained from sequencing efforts. In this work, we introduce information-theoretic based approaches to score protein-protein functional interaction pairs predicted from protein sequence similarity and conserved protein signature matches. The proposed schemes are effective for data-driven scoring of connections between protein pairs. We applied these schemes to the Mycobacterium tuberculosis proteome to produce a homology-based functional network of the organism with a high confidence and coverage. We use the network for predicting functions of uncharacterised proteins

Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study

Diuretics have photosensitising properties. However, little is known about how these diuretics affect the risk of skin cancers. In North Jutland County, Denmark, we investigated whether the use of photosensitising diuretics was associated with an increased risk for developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM). From the cancer registry, we identified primary cases of BCC, SCC and MM during the period of 1989–2003. We selected four population controls for each case from the Danish Civil Registration System, matched on age and gender. Prescriptions for photosensitising diuretics before cancer diagnosis were ascertained in the county's Prescription Database. We used conditional logistic regression to compute incidence rate ratio (IRR), controlling for the chronic medical conditions and for the previous use of oral glucocorticoids. We found an increased risk of SCC (IRR of 1.79 (95% confidence interval (CI): 1.45–2.21)) and MM (IRR of 1.43 (95% CI: 1.09–1.88)) among users of combined amiloride and hydrochlorothiazide therapy. An increased risk of MM (IRR of 3.30 (95% CI: 1.34–8.10)) was found among users of indapamide. We found little associations with risk of BCC. Our findings provide evidence that the use of some photosensitising diuretics is associated with an increased risk for SCC and MM

“My Lung Disease Won’t Go Away, it’s There to Stay”: Profiles of Adaptation to Functional Limitations in Workers with Asthma and COPD

Purpose Earlier research has shown that adaptation (i.e., the way in which employees cope with limitations resulting from their disease) is associated with sick leave. Our aim was to investigate signs of adequate or inadequate adaptation in employees with asthma and COPD. Methods A Q-methodological study was carried out among 34 workers with asthma or COPD. Results Four adaptation profiles were distinguished: the eager, the adjusted, the cautious, and the worried workers. The adaptation profiles provide insight into the different ways in which workers with asthma and COPD cope with their illness at work. Conclusions The adaptation profiles serve as a starting point for the design of appropriate (occupational) care. The eager workers experience little difficulties at work; the cautious workers may need assistance in learning how to accept their disease; the worried workers need reassurance, and may need reactivation; the adjusted workers deserve extra attention, and, when necessary, advice on how to live with their asthma or COPD

Pre- and early-postnatal nutrition modify gene and protein expressions of muscle energy metabolism markers and phospholipid fatty acid composition in a muscle type specific manner in sheep.

We previously reported that undernutrition in late fetal life reduced whole-body insulin sensitivity in adult sheep, irrespective of dietary exposure in early postnatal life. Skeletal muscle may play an important role in control of insulin action. We therefore studied a range of putative key muscle determinants of insulin signalling in two types of skeletal muscles (longissimus dorsi (LD) and biceps femoris (BF)) and in the cardiac muscle (ventriculus sinister cordis (VSC)) of sheep from the same experiment. Twin-bearing ewes were fed either 100% (NORM) or 50% (LOW) of their energy and protein requirements during the last trimester of gestation. From day-3 postpartum to 6-months of age (around puberty), twin offspring received a high-carbohydrate-high-fat (HCHF) or a moderate-conventional (CONV) diet, whereafter all males were slaughtered. Females were subsequently raised on a moderate diet and slaughtered at 2-years of age (young adults). The only long-term consequences of fetal undernutrition observed in adult offspring were lower expressions of the insulin responsive glucose transporter 4 (GLUT4) protein and peroxisome proliferator-activated receptor gamma, coactivator 1α (PGC1α) mRNA in BF, but increased PGC1α expression in VSC. Interestingly, the HCHF diet in early postnatal life was associated with somewhat paradoxically increased expressions in LD of a range of genes (but not proteins) related to glucose uptake, insulin signalling and fatty acid oxidation. Except for fatty acid oxidation genes, these changes persisted into adulthood. No persistent expression changes were observed in BF and VSC. The HCHF diet increased phospholipid ratios of n-6/n-3 polyunsaturated fatty acids in all muscles, even in adults fed identical diets for 1½ years. In conclusion, early postnatal, but not late gestation, nutrition had long-term consequences for a number of determinants of insulin action and metabolism in LD. Tissues other than muscle may account for reduced whole body insulin sensitivity in adult LOW sheep

Merozoite release from Plasmodium falciparum-infected erythrocytes involves the transfer of DiIC16 from infected cell membrane to Maurer’s clefts

Merozoite release from infected erythrocytes is a complex process, which is still not fully understood. Such process was characterised at ultra-structural level in this work by labelling erythrocyte membrane with a fluorescent lipid probe and subsequent photo-conversion into an electron-dense precipitate. A lipophilic DiIC16 probe was inserted into the infected erythrocyte surface and the transport of this phospholipid analogue through the erythrocyte membrane was followed up during 48 h of the asexual erythrocyte cycle. The lipid probe was transferred from infected erythrocyte membranes to Maurer’s clefts during merozoite release, thereby indicating that these membranes remained inside host cells after parasite release. Fluorescent structures were never observed inside infected erythrocytes preceding merozoite exit and merozoites released from infected erythrocyte were not fluorescent. However, specific precipitated material was localised bordering the parasitophorous vacuole membrane and tubovesicular membranes when labelled non-infected erythrocytes were invaded by merozoites. It was revealed that lipids were interchangeable from one membrane to another, passing from infected erythrocyte membrane to Maurer’s clefts inside the erythrocyte ghost, even after merozoite release. Maurer’s clefts became photo-converted following merozoite release, suggesting that these structures were in close contact with infected erythrocyte membrane during merozoite exit and possibly played some role in malarial parasite exit from the host cell

Child and Family Therapy Process: Concordance of Therapist and Observational Perspectives

The objective of this study is to examine the characteristics of outpatient mental health services delivered in community-based outpatient clinics, comparing information obtained from two different sources, therapists serving children and families, and observational coders viewing tapes of the same treatment sessions. Videotaped therapy sessions were rated by therapists and independent coders regarding goals and strategies pursued during each session. Sixty-three sessions were taped of outpatient care provided to 18 children and their caregivers by 11 therapists. Children were 4–13 years old and families were receiving services at least in part due to reported child behavior problems, confirmed by ratings from the Child Behavior Checklist and Conners Parent Rating Scale—Revised. Analyses assessed the frequency, type, and intensity of goals and strategies pursued in therapy sessions from both therapist and observational coders’ perspectives. Reliability of observer ratings and correspondence between therapist and observer reports were also examined. The reliability of observational coding of goals and strategies was moderate to good, with 76% of 39 codes having ICCs of .5 or greater. Therapists reported pursuing 2.5 times more goals and strategies per session, on average, than identified by observational coders. Correspondence between therapists and coders about the occurrence of specific goals and strategies in treatment sessions was low, with 20.5% of codes having a Kappa of .4 or higher. Substantial differences exist in what therapists and independent coders report as occurring in outpatient treatment sessions. Both perspectives suggest major differences between the content of services provided in community-based outpatient clinics and the structure of evidence-based programs, which emphasize intense pursuit of a small number of goals and strategies in each treatment session. Implications of the findings for quality improvement efforts in community-based mental health care settings are discussed

An integrated approach to a combinatorial optimisation problem

Funding: MRC grant MR/S003819/1 and Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities.We take inspiration from a problem from the healthcare domain, where patients with several chronic conditions follow different guidelines designed for the individual conditions, and where the aim is to find the best treatment plan for a patient that avoids adverse drug reactions, respects patient’s preferences and prioritises drug efficacy. Each chronic condition guideline can be abstractly described by a directed graph, where each node indicates a treatment step (e.g., a choice in medications or resources) and has a certain duration. The search for the best treatment path is seen as a combinatorial optimisation problem and we show how to select a path across the graphs constrained by a notion of resource compatibility. This notion takes into account interactions between any finite number of resources, and makes it possible to express non-monotonic interactions. Our formalisation also introduces a discrete temporal metric, so as to consider only simultaneous nodes in the optimisation process. We express the formal problem as an SMT problem and provide a correctness proof of the SMT code by exploiting the interplay between SMT solvers and the proof assistant Isabelle/HOL. The problem we consider combines aspects of optimal graph execution and resource allocation, showing how an SMT solver can be an alternative to other approaches which are well-researched in the corresponding domains.Postprin

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study

Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo feedback-controlled design and to explore the initial efficacy of individualized EEG-neurofeedback training in children with ADHD. Fourteen children (8–15 years) with ADHD defined according to the DSM-IV-TR criteria were randomly allocated to 30 sessions of EEG-neurofeedback (n = 8) or placebo feedback (n = 6). Safety measures (adverse events and sleep problems), ADHD symptoms and global improvement were monitored. With respect to feasibility, all children completed the study and attended all study visits and training sessions. No significant adverse effects or sleep problems were reported. Regarding the expectancy, 75% of children and their parent(s) in the active neurofeedback group and 50% of children and their parent(s) in the placebo feedback group thought they received placebo feedback training. Analyses revealed significant improvements of ADHD symptoms over time, but changes were similar for both groups. This pilot study shows that it is feasible to conduct a rigorous placebo-controlled trial to investigate the efficacy of neurofeedback training in children with ADHD. However, a double-blind design may not be feasible since using automatic adjusted reward thresholds may not work as effective as manually adjusted reward thresholds. Additionally, implementation of active learning strategies may be an important factor for the efficacy of EEG-neurofeedback training. Based on the results of this pilot study, changes are made in the design of the ongoing study