Multidimensional family therapy decreases the rate of externalising behavioural disorder symptoms in cannabis abusing adolescents: Outcomes of the INCANT trial

Background: US-based trials have shown that Multidimensional Family Therapy (MDFT) not only reduces substance abuse among adolescents, but also decreases mental and behavioural disorder symptoms, most notably externalising symptoms. In the INCANT trial, MDFT decreased the rate of cannabis dependence among Western European youth. We now focus on other INCANT outcomes, i.e., lessening of co-morbidity symptoms and improvement of family functioning.Methods: INCANT was a randomised controlled trial comparing MDFT with individual therapy (IP) at and across sites in Berlin, Brussels, Geneva, The Hague, and Paris. We recruited 450 boys and girls aged 13 up to 18 years with a cannabis use disorder, and their parent(s), and followed them for 12 months. Mental and behavioural characteristics (classified as 'externalising' or 'internalising') and family conflict and cohesion were assessed.Results: From intake through 12 months, MDFT and IP groups improved on all outcome measures. Models including treatment, site, and referral source showed that MDFT outperformed IP in reducing externalising symptoms.Adolescents were either self-referred to treatment (mostly on the initiative from people close to the teen) or referred under some measure of coercion by an external authority. These two groups reacted equally well to treatment.Conclusions: Both MDFT and IP reduced the rate of externalising and internalising symptoms and improved family functioning among adolescents with a cannabis use disorder. MDFT outperformed IP in decreasing the rate of externalising symptoms. Contrary to common beliefs among therapists in parts of Western Europe, the 'coerced' adolescents did at least as well in treatment as the self-referred adolescents.MDFT shows promise as a treatment for both substance use disorders and externalising symptoms

Long-term field performance of a polyester-based long-lasting insecticidal mosquito net in rural Uganda

<p>Abstract</p> <p>Background</p> <p>In order to evaluate whether criteria for LLIN field performance (phase III) set by the WHO Pesticide Evaluation Scheme are met, first and second generations of one of these products, PermaNet^®, a polyester net using the coating technology were tested.</p> <p>Methods</p> <p>A randomized, double blinded study design was used comparing LLIN to conventionally treated nets and following LLIN for three years under regular household use in rural conditions. Primary outcome measures were deltamethrin residue and bioassay performance (60 minute knock-down and 24 hour mortality after a three minute exposure) using a strain of <it>Anopheles gambiae s.s</it>. sensitive to pyrethroid insecticides.</p> <p>Results</p> <p>Baseline concentration of deltamethrin was within targets for all net types but was rapidly lost in conventionally treated nets and first generation PermaNet^®with median of 0.7 and 2.5 mg/m²after six months respectively. In contrast, second generation PermaNet^®retained insecticide well and had 41.5% of baseline dose after 36 months (28.7 mg/m²). Similarly, vector mortality and knockdown dropped to 18% and 70% respectively for first generation LLIN after six months but remained high (88.5% and 97.8% respectively) for second generation PermaNet^®after 36 months of follow up at which time 90.0% of nets had either a knockdown rate ≥ 95% or mortality rate ≥ 80%.</p> <p>Conclusion</p> <p>Second generation PermaNet^®showed excellent results after three years of field use and fulfilled the WHOPES criteria for LLIN. Loss of insecticide on LLIN using coating technology under field conditions was far more influenced by factors associated with handling rather than washing.</p

Evidence for Cognitive Impairment in Mastocytosis: Prevalence, Features and Correlations to Depression

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3rd edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

An RNA Transport System in Candida albicans Regulates Hyphal Morphology and Invasive Growth

Localization of specific mRNAs is an important mechanism through which cells achieve polarity and direct asymmetric growth. Based on a framework established in Saccharomyces cerevisiae, we describe a She3-dependent RNA transport system in Candida albicans, a fungal pathogen of humans that grows as both budding (yeast) and filamentous (hyphal and pseudohyphal) forms. We identify a set of 40 mRNAs that are selectively transported to the buds of yeast-form cells and to the tips of hyphae, and we show that many of the genes encoded by these mRNAs contribute to hyphal development, as does the transport system itself. Although the basic system of mRNA transport is conserved between S. cerevisiae and C. albicans, we find that the cargo mRNAs have diverged considerably, implying that specific mRNAs can easily move in and out of transport control over evolutionary timescales. The differences in mRNA cargos likely reflect the distinct selective pressures acting on the two species

Molecular and Evolutionary Bases of Within-Patient Genotypic and Phenotypic Diversity in Escherichia coli Extraintestinal Infections

Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that the observed diversity resembled results obtained in experimental evolution studies. Whatever the mechanisms leading to diversity, our results have strong medical implications in terms of the need for more extensive isolate testing before deciding on antibiotic therapies

The Pleiotropic CymR Regulator of Staphylococcus aureus Plays an Important Role in Virulence and Stress Response

We have characterized a novel pleiotropic role for CymR, the master regulator of cysteine metabolism. We show here that CymR plays an important role both in stress response and virulence of Staphylococcus aureus. Genes involved in detoxification processes, including oxidative stress response and metal ion homeostasis, were differentially expressed in a ΔcymR mutant. Deletion of cymR resulted in increased sensitivity to hydrogen peroxide-, disulfide-, tellurite- and copper-induced stresses. Estimation of metabolite pools suggests that this heightened sensitivity could be the result of profound metabolic changes in the ΔcymR mutant, with an increase in the intracellular cysteine pool and hydrogen sulfide formation. Since resistance to oxidative stress within the host organism is important for pathogen survival, we investigated the role of CymR during the infectious process. Our results indicate that the deletion of cymR promotes survival of S. aureus inside macrophages, whereas virulence of the ΔcymR mutant is highly impaired in mice. These data indicate that CymR plays a major role in virulence and adaptation of S. aureus for survival within the host

The Liquid Argon In A Testbeam (LArIAT) Experiment

The LArIAT liquid argon time projection chamber, placed in a tertiary beam of charged particles at the Fermilab Test Beam Facility, has collected large samples of pions, muons, electrons, protons, and kaons in the momentum range 300-1400 MeV/c. This paper describes the main aspects of the detector and beamline, and also reports on calibrations performed for the detector and beamline components

The Fecal Viral Flora of Wild Rodents

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals

Measurement of the (π−\pi^-, Ar) total hadronic cross section at the LArIAT experiment

We present the first measurement of the negative pion total hadronic cross section on argon, which we performed at the Liquid Argon In A Testbeam (LArIAT) experiment. All hadronic reaction channels, as well as hadronic elastic interactions with scattering angle greater than 5~degrees are included. The pions have a kinetic energies in the range 100-700~MeV and are produced by a beam of charged particles impinging on a solid target at the Fermilab Test Beam Facility. LArIAT employs a 0.24~ton active mass Liquid Argon Time Projection Chamber (LArTPC) to measure the pion hadronic interactions. For this measurement, LArIAT has developed the ``thin slice method", a new technique to measure cross sections with LArTPCs. While generally higher than the prediction, our measurement of the ($\pi^-$,Ar) total hadronic cross section is in agreement with the prediction of the Geant4 model when considering a model uncertainty of $\sim$5.1\%.Comment: 15 pages, 15 figures, 3 tables, accepted by PR