Early developmental, temperamental and educational problems in ‘substance use disorder’ patients with and without ADHD. Does ADHD make a difference?

Introduction: The prevalence of ADHD among patients with substance use disorder (SUD) is substantial. This study addressed the following research questions: Are early developmental, temperamental and educational problems overrepresented among SUD patients with ADHD compared to SUD patients without ADHD? Do this comorbid group receive early help for their ADHD, and are there signs of self-medicating with illicit central stimulants? Method: An international, multi-centre cross-sectional study was carried out involving seven European countries, with 1205 patients in treatment for SUD. The mean age was 40 years and 27% of the sample was female. All par- ticipants were interviewed with the Mini International Neuropsychiatric Interview Plus and the Conners' Adult ADHD Diagnostic Interview for DSM-IV. Results: SUD patients with ADHD (n = 196; 16.3% of the total sample) had a significantly slower infant develop- ment than SUD patients without ADHD (n = 1,009; 83.4%), had greater problems controlling their temperament, and had lower educational attainment. Only 24 (12%) of the current ADHD positive patients had been diagnosed and treated during childhood and/or adolescence. Finally, SUD patients with ADHD were more likely to have central stimulants or cannabis as their primary substance of abuse, whereas alcohol use was more likely to be the primary substance of abuse in SUD patients without ADHD. Conclusion: The results emphasize the importance of early identification of ADHD and targeted interventions in the health and school system, as well as in the addiction field.

Risk factors for borderline personality disorder in treatment seeking patients with a substance use disorder: an international multicenter study

Borderline personality disorder (BPD) and substance use disorders (SUDs) often co-occur, partly because they share risk factors. In this international multicenter study, risk factors for BPD were examined for SUD patients. In total, 1,205 patients were comprehensively examined by standardized interviews and questionnaires on psychiatric diagnosis and risk factors, and it was found that 1,033 (85.7%) had SUDs without BPD (SUD) and 172 (14.3%) had SUD with BPD (SUD + BPD). SUD + BPD patients were significantly younger, more often females and more often diagnosed with comorbid adult attention deficit/hyperactivity disorder. SUD + BPD patients did not differ from SUD patients on most risk factors typical for SUD such as maternal use of drugs during pregnancy or parents having any SUD. However, SUD + BPD patients did have a higher risk of having experienced emotional and physical abuse, neglect, or family violence in childhood compared to SUD patients, suggesting that child abuse and family violence are BPD-specific risk factors in patients with SUDs. © 2015 S. Karger AG, Basel.

Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

The genomic substrate for adaptive radiation in African cichlid fish

Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Effect of Health Risk Assessment and Counselling on Health Behaviour and Survival in Older People: A Pragmatic Randomised Trial.

BACKGROUND Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

Osseointegration of titanium implants functionalised with phosphoserine-tethered poly(epsilon-lysine) dendrons: a comparative study with traditional surface treatments in sheep

The aim of this study was to analyse the osseointegrative potential of phosphoserine-tethered dendrons when applied as surface functionalisation molecules on titanium implants in a sheep model after 2 and 8 weeks of implantation. Uncoated and dendron-coated implants were implanted in six sheep. Sandblasted and etched (SE) or porous additive manufactured (AM) implants with and without additional dendron functionalisation (SE-PSD; AM-PSD) were placed in the pelvic bone. Three implants per group were examined histologically and six implants were tested biomechanically. After 2 and 8 weeks the bone-to-implant contact (BIC) total values of SE implants (43.7 ± 12.2; 53.3 ± 9.0 %) and SE-PSD (46.7 ± 4.5; 61.7 ± 4.9 %) as well as AM implants (20.49 ± 5.1; 43.9 ± 9.7 %) and AM-PSD implants (19.7 ± 3.5; 48.3 ± 15.6 %) showed no statistically significant differences. For SE-PSD and AM-PSD a separate analysis of only the cancellous BIC demonstrated a statistically significant difference after 2 and 8 weeks. Biomechanical findings proved the overall increased stability of the porous implants after 8 weeks. Overall, the great effect of implant macro design on osseointegration was further supported by additional phosphoserine-tethered dendrons for SE and AM implants.

AsaGEI2b: a new variant of a genomic island identified in the Aeromonas salmonicida subsp. salmonicida JF3224 strain isolated from a wild fish in Switzerland.

Aeromonas salmonicida subsp. salmonicida is the causal agent of furunculosis in salmonids. We recently identified a group of genomic islands (AsaGEI) in this bacterium. AsaGEI2a, one of these genomic islands, has almost exclusively been identified in isolates from North America. To date, Aeromonas salmonicida subsp. salmonicida JF3224, a strain isolated from a wild brown trout (Salmo trutta) caught in Switzerland, was the only European isolate that appeared to bear AsaGEI2a. We analyzed the genome of JF3224 and showed that the genomic island in JF3224 is a new variant of AsaGEI, which we have called AsaGEI2b. While AsaGEI2b shares the same integrase gene and insertion site as AsaGEI2a, it is very different in terms of many other features. Additional genomic investigations combined with PCR genotyping revealed that JF3224 is sensitive to growth at 25°C, leading to insertion sequence-dependent rearrangement of the locus on the pAsa5 plasmid that encodes a type three secretion system, which is essential for the virulence of the bacterium. The analysis of the JF3224 genome confirmed that AsaGEIs are accurate indicators of the geographic origins of A. salmonicida subsp. salmonicida isolates and is another example of the susceptibility of the pAsa5 plasmid to DNA rearrangements.

A nearby M Star with tree Transitting Supter-Earths Discovered by K2

Small, cool planets represent the typical end-products of planetary formation. Studying the architectures of these systems, measuring planet masses and radii, and observing these planets' atmospheres during transit directly informs theories of planet assembly, migration, and evolution. Here we report the discovery of three small planets orbiting a bright (K-s = 8.6 mag) M0 dwarf using data collected as part of K2, the new ecliptic survey using the repurposed Kepler spacecraft. Stellar spectroscopy and K2 photometry indicate that the system hosts three transiting planets with radii 1.5-2.1 R-circle plus, straddling the transition region between rocky and increasingly volatile-dominated compositions. With orbital periods of 10-45 days the planets receive just 1.5-10x the flux incident on Earth, making these some of the coolest small planets known orbiting a nearby star; planet d is located near the inner edge of the system's habitable zone. The bright, low-mass star makes this system an excellent laboratory to determine the planets' masses via Doppler spectroscopy and to constrain their atmospheric compositions via transit spectroscopy. This discovery demonstrates the ability of K2 and future space-based transit searches to find many fascinating objects of interest.