Longer-term effectiveness of systemic family therapy compared with treatment as usual for young people after self-harm: An extended follow up of pragmatic randomised controlled trial

Background: Self-harm in adolescents is common and repetition frequent. Evidence for effective interventions to reduce self-harm is limited. Long term follow-up of existing studies is rare. Methods: Extended follow up, from 18 to at least 36-months, of the SHIFT trial: a pragmatic, multi-centre, individually-randomised, controlled trial involving young people (11–17) who had self-harmed at least twice and presented to Child & Adolescent Mental Health Services (CAMHS). SHIFT evaluated manualised family therapy (FT) versus treatment as usual (TAU) in reducing repetition of self-harm leading to hospital attendance 18 months post-randomisation. We obtained ONS mortality data, adult mental health data, and further details of hospital attendance from routine Hospital Episode Statistics (HES) data plus researcher follow-up. We assessed longer-term differences in outcome using multivariable Cox Proportional Hazards regression analysis, and assessed all-cause mortality and morbidity relating to hospital attendances for reasons other than self-harm. Study registration: ISRCTN 59793150 Outcomes: The original sample of 832 were randomised between April 2010 and December 2013. Extended follow-up continued until February 2017 for a median 55·4 months (range 0–82·5 months), providing post 18-month data for 804 (96·6%) participants, of whom 785 (94·4%) had a minimum of 36-months follow-up. There was no evidence of a between-group difference in the primary outcome during the extended follow-up period (Hazard Ratio (HR) 1·03; 95% CI: 0·83, 1·28; p-value=0·78), consistent with our findings in the original trial with 18 months follow-up (HR 1·14, 95% CI 0·87, 1·49; p-value 0·33). There was a reduced rate of self-harm in older participants aged 15–17 (HR 0·7, 95% CI 0·56, 0·88), as compared with those aged 11–14; and significantly increased rates of self-harm in participants whose index episode combined self-injury and poisoning (HR 1·8, 95% CI 1·2, 2·7). Two deaths were reported during the extended follow up period. Interpretation: For adolescents referred to CAMHS after self-harm, having self-harmed at least once before, trial FT confers no benefits over TAU in reducing subsequent hospitalisation for self-harm over 18 months or 36 months. Funding: NIHR HTA Reference: 07/33/0

Self-Harm Intervention: Family Therapy (SHIFT), a study protocol for a randomised controlled trial of family therapy versus treatment as usual for young people seen after a second or subsequent episode of self-harm

Background: Self-harm is common in the community with a lifetime prevalence of 13 %. It is associated with an elevated risk of overall mortality and suicide. People who harm themselves are high users of public services. Estimates of the 1-year risk of repetition vary between 5 and 15 % per year. Currently, limited evidence exists on the effectiveness of clinical interventions for young people who engage in self-harm. Recent reviews have failed to demonstrate any effect on reducing repetition of self-harm among adolescents receiving a range of treatment approaches. Family factors are particularly important risk factors associated with fatal and non-fatal self-harm among children and adolescents. Family therapy focuses on the relationships, roles and communication patterns between family members, but there have been relatively few studies of specifically family-focused interventions with this population. The Self-Harm Intervention: Family Therapy (SHIFT) Trial was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (grant no. 07/33/01) following a commissioned call for this research. Methods/Design: SHIFT is a pragmatic, phase III, multicentre, individually randomised, controlled trial comparing Family Therapy (FT) with treatment as usual (TAU) for adolescents aged 11 to 17 who have engaged in at least two episodes of self-harm. Both therapeutic interventions were delivered within the National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) in England. Participants and therapists were, of necessity, aware of treatment allocation, but the researchers were blind to the allocations to allow unbiased collection of follow-up data. Primary outcome data (repetition of self-harm leading to hospital attendance 18 months post-randomisation) were collected from the Health and Social Care Information Centre (HSCIC), augmented by directed searches of medical records at Acute Trusts. Secondary outcome data (including suicidal intent, depression, hopelessness and health economics) were collected at 12 and 18 months post-randomisation via researcher-participant interviews and by post at 3 and 6 months. Discussion: SHIFT will provide a well-powered evaluation of the clinical and cost effectiveness of Family Therapy for young people who have self-harmed on more than one occasion. The study will be reported in 2016, and the results will inform clinical practice thereafter

Modeling the Control of Trypanosomiasis Using Trypanocides or Insecticide-Treated Livestock

In Uganda, cattle are an important reservoir for Trypanosoma brucei rhodesiense, the causative agent of Rhodesian sleeping sickness (human African trypanosomiasis), transmitted by tsetse flies Glossina fuscipes fuscipes, which feed on cattle, humans, and wild vertebrates, particularly monitor lizards. Trypanosomiasis can be controlled by treating livestock with trypanocides or insecticide – killing parasites or vectors, respectively. Mathematical modeling of trypanosomiasis was used to compare the impact of drug- and insecticide-based interventions on R0 with varying densities of cattle, humans and wild hosts. Intervention impact changes with the number of cattle treated and the proportion of bloodmeals tsetse take from cattle. R0 was always reduced more by treating cattle with insecticide rather than trypanocides. In the absence of wild hosts, the model suggests that control of sleeping sickness (R0<1) could be achieved by treating ∼65% of cattle with trypanocides or ∼20% with insecticide. Required coverage increases as wild mammals provide increasing proportion of tsetse bloodmeals: if 60% of non-human bloodmeals are from wild hosts then all cattle have to be treated with insecticide. Conversely, it is reduced if lizards, which do not harbor trypanosomes, are important hosts and/or if insecticides are used at a scale where tsetse numbers decline

Towards an integrated approach in surveillance of vector-borne diseases in Europe

Vector borne disease (VBD) emergence is a complex and dynamic process. Interactions between multiple disciplines and responsible health and environmental authorities are often needed for an effective early warning, surveillance and control of vectors and the diseases they transmit. To fully appreciate this complexity, integrated knowledge about the human and the vector population is desirable. In the current paper, important parameters and terms of both public health and medical entomology are defined in order to establish a common language that facilitates collaboration between the two disciplines. Special focus is put on the different VBD contexts with respect to the current presence or absence of the disease, the pathogen and the vector in a given location. Depending on the context, whether a VBD is endemic or not, surveillance activities are required to assess disease burden or threat, respectively. Following a decision for action, surveillance activities continue to assess trends

Genetic Determinants of Time Perception Mediated by the Serotonergic System

Background: The present study investigates neurobiological underpinnings of individual differences in time perception. Methodology: Forty-four right-handed Russian Caucasian males (18–35 years old) participated in the experiment. The polymorphism of the genes related to the activity of serotonin (5-HT) and dopamine (DA)-systems (such as 5-HTT, 5HT2a, MAOA, DAT, DRD2, COMT) was determined upon the basis of DNA analysis according to a standard procedure. Time perception in the supra-second range (mean duration 4.8 s) was studied, using the duration discrimination task and parametric fitting of psychometric functions, resulting in individual determination of the point of subjective equality (PSE). Assuming the ‘dual klepsydra model ’ of internal duration representation, the PSE values were transformed into equivalent values of the parameter k (kappa), which is a measure of the ‘loss rate ’ of the duration representation. An association between time representation parameters (PSE and k, respectively) and 5-HT-related genes was found, but not with DArelated genes. Higher ‘loss rate ’ (k) of the cumulative duration representation were found for the carriers of genotypes characterized by higher 5-HT transmission, i.e., 1) lower 5-HT reuptake, known for the 5-HTTLPR SS polymorphism compared with LL, 2) lower 5-HT degradation, described for the ‘low expression ’ variant of MAOA VNTR gene compared with ‘high expression ’ variant, and 3) higher 5-HT2a receptor density, proposed for the TT polymorphism of 5-HT2a T102C gene compared with CC

Speaker- versus listener-oriented disfluency: A re-examination of arguments and assumptions from autism spectrum disorder

We re-evaluate conclusions about disfluency production in high-functioning forms of autism spectrum disorder (HFA). Previous studies examined individuals with HFA to address a theoretical question regarding speaker- and listener-oriented disfluencies. Individuals with HFA tend to be self-centric and have poor pragmatic language skills, and should be less likely to produce listener-oriented disfluency. However, previous studies did not account for individual differences variables that affect disfluency. We show that both matched and unmatched controls produce fewer repairs than individuals with HFA. For silent pauses, there was no difference between matched controls and HFA, but both groups produced more than unmatched controls. These results identify limitations in prior research and shed light on the relationship between autism spectrum disorders and disfluent speech

The distribution of standard deviations applied to high throughput screening

High throughput screening (HTS) assesses compound libraries for “activity” using target assays. A subset of HTS data contains a large number of sample measurements replicated a small number of times providing an opportunity to introduce the distribution of standard deviations (DSD). Applying the DSD to some HTS data sets revealed signs of bias in some of the data and discovered a sub-population of compounds exhibiting high variability which may be difficult to screen. In the data examined, 21% of 1189 such compounds were pan-assay interference compounds. This proportion reached 57% for the most closely related compounds within the sub-population. Using the DSD, large HTS data sets can be modelled in many cases as two distributions: a large group of nearly normally distributed “inactive” compounds and a residual distribution of “active” compounds. The latter were not normally distributed, overlapped inactive distributions – on both sides –, and were larger than typically assumed. As such, a large number of compounds are being misclassified as “inactive” or are invisible to current methods which could become the next generation of drugs. Although applied here to HTS, it is applicable to data sets with a large number of samples measured a small number of times

Reduced Mitochondrial Membrane Potential is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo- ATPase

Background: Isometamidium is the main prophylactic drug used to prevent the infection of livestock with trypanosomes that cause Animal African Trypanosomiasis. As well as the animal infective trypanosome species, livestock can also harbor the closely related human infective subspecies T. b. gambiense and T. b. rhodesiense. Resistance to isometamidium is a growing concern, as is cross-resistance to the diamidine drugs diminazene and pentamidine. Methodology/Principal Findings: Two isometamidium resistant Trypanosoma brucei clones were generated (ISMR1 and ISMR15), being 7270- and 16,000-fold resistant to isometamidium, respectively, which retained their ability to grow in vitro and establish an infection in mice. Considerable cross-resistance was shown to ethidium bromide and diminazene, with minor cross-resistance to pentamidine. The mitochondrial membrane potentials of both resistant cell lines were significantly reduced compared to the wild type. The net uptake rate of isometamidium was reduced 2-3-fold but isometamidium efflux was similar in wild-type and resistant lines. Fluorescence microscopy and PCR analysis revealed that ISMR1 and ISMR15 had completely lost their kinetoplast DNA (kDNA) and both lines carried a mutation in the nuclearly encoded γ subunit gene of F1 ATPase, truncating the protein by 22 amino acids. The mutation compensated for the loss of the kinetoplast in bloodstream forms, allowing near-normal growth, and conferred considerable resistance to isometamidium and ethidium as well as significant resistance to diminazene and pentamidine, when expressed in wild type trypanosomes. Subsequent exposure to either isometamidium or ethidium led to rapid loss of kDNA and a further increase in isometamidium resistance. Conclusions/Significance: Sub-lethal exposure to isometamidium gives rise to viable but highly resistant trypanosomes that, depending on sub-species, are infective to humans and cross-resistant to at least some diamidine drugs. The crucial mutation is in the F1 ATPase γ subunit, which allows loss of kDNA and results in a reduction of the mitochondrial membrane potential

Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities