Improving Outcomes for Solid-Organ Transplant Recipients At Risk from Cytomegalovirus Infection: Late-Onset Disease and Indirect Consequences

Cytomegalovirus (CMV) is one of the most important pathogens following solid-organ transplantation, and effective prevention of CMV infection is a priority. The long-term control of CMV infection is dependent, in part, on the development of CMV-specific T cells, and controversy exists regarding whether CMV prophylaxis may prevent this. Although preemptive therapy is beneficial for the prevention of CMV disease, monitoring of viral levels in the blood does not always reflect what is occurring in tissues. Persistent low-level CMV infection has been associated with indirect consequences, such as transplant-associated vasculopathy, posttransplantation diabetes, an increased risk of opportunistic infection, and graft rejection. The issues surrounding preventive strategies for CMV disease following solid-organ transplantation are reviewed. We argue that prophylaxis is more effective than preemptive therapy; extending the duration of prophylaxis to the period of less intense immunosuppression could protect patients from late-onset disease, as well as from the indirect effects of CMV infectio

Conditions for the sliding-bouncing transition for the interaction of a bubble with an inclined wall

In this study we analyze the interaction of a single rising bubble with an inclined wall. We conduct experiments considering different liquids and bubble sizes, to cover a wide range of Reynolds and Weber numbers, with wall angles from nearly horizontal to nearly vertical. For all cases, the bubble initially collides with the wall; after the initial interaction, in accord with previous studies, the bubble either steadily slides on the wall or ascends, colliding repeatedly with it. Considering a force balance for the bubble motion on the wall, we propose a set of conditions for the transition from sliding to bouncing that is validated with the present and previous data

Safety and efficacy of eculizumab in adult and pediatric patients with aHUS, with or without baseline dialysis

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Egg production in the euryhaline tilapia, Sarotherodon melanotheron heudelotii, experimentally maintained in fresh, sea and hypersaline waters

Through the experiments presented here we wanted to test whether egg production of the black-chinned tilapia Sarotherodon melanotheron heudelotii under experimental conditions varies as a function of ambient salinity (fresh waters vs. sea waters vs. hypersaline waters, 0, 35 and 70, respectively) and whether these responses differ between fish acclimated within a few weeks from fresh water to saline and hypersaline environments (experiments E1 and E2, monitoring over 10 and 18 weeks), and individuals born and raised all life long at the experimental salinities (E3, monitoring over 18 weeks). In total, 233 spawns were collected. In each of the three experiments, the reproductive investment (gram of egg per gram of female over 2 weeks) did not differ between salinities of 0 and 35, whereas it was 2-3 times lower at 70 than at 0-35, because of lower spawning frequency (E1-E3), smaller clutch size (E1) and lower spawn mass (E1-E3). Finally, fish acclimated to salinity from fresh water over a few weeks and those maintained at a particular salinity all life long showed similar reproductive traits, thereby emphasizing the remarkable physiological plasticity of this species

Plasticity of gene expression according to salinity in the testis of broodstock and F1 black-chinned tilapia, Sarotherodon melanotheron heudelotii

The black-chinned tilapia Sarotherodon melanotheron heudelotii Ruppell 1852 (Teleostei, Cichlidae) displays remarkable acclimation capacities. When exposed to drastic changes of salinity, which can be the case in its natural habitat, it develops quick physiological responses and keeps reproducing. The present study focused on the physiological impact of salinity on male reproductive capacities, using gene expression as a proxy of acclimation process. Two series of experimental fish were investigated: the first one was composed of fish maintained in freshwater for several generations and newly acclimated to salinities of 35 and 70, whereas the second one consisted of the descendants of the latter born and were raised under their native salinity. Expression patterns of 43 candidate genes previously identified from the testes of wild males was investigated in the three salinities and two generations. Twenty of them showed significant expression differences between salinities, and their predicted function revealed that most of them are involved in the osmotic tolerance of sperm cells and/or in the maintenance of sperm motility. A high level of expression variation was evidenced, especially for fish maintained in freshwater. In spite of this, gene expression patterns allowed the differentiation between fish raised in freshwater and those maintained in hypersaline water in both generations. Altogether, the results presented here suggest that this high variability of expression is likely to ensure the reproductive success of this species under varying salinities

NPHS2 mutation analysis shows genetic heterogeneityof steroid-resistant nephrotic syndrome and lowpost-transplant recurrence

NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence.BackgroundMutations of NPHS2 are causative in familial autosomal-recessive (AR) and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the spectrum of NPHS2 mutations and to establish genotype-phenotype correlations.MethodsNPHS2 mutation analysis was performed in 338 patients from 272 families with SRNS: 81 families with AR SRNS, 172 patients with sporadic SRNS, and 19 patients with diffuse mesangial sclerosis (DMS).ResultsTwenty-six different pathogenic NPHS2 mutations were detected, including 13 novel mutations. The mutation detection rate was 43% for familial AR and 10.5% for sporadic SRNS, confirming genetic heterogeneity. No pathogenic NPHS2 mutations were found in DMS patients. Age at onset in patients with two pathogenic mutations was earlier, especially in cases with frameshift, truncating, and the R138Q missense mutations. Patients with only one NPHS2 mutation or variant had late-onset NS. Triallelic inheritance was observed in one patient with a homozygous R138Q mutation and a de novo NPHS1 mutation. Among 32 patients with two NPHS2 mutations who underwent kidney transplantation, only one developed late recurrence of focal segmental glomerulosclerosis (FSGS). Among 25 patients with sporadic SRNS and post-transplantation recurrence, we detected a heterozygous NPHS2 mutation in one case, and heterozygous variants/polymorphisms in 3 cases.ConclusionPatients with two pathogenic NPHS2 mutations present with early-onset SRNS and very low incidence of post-transplantation recurrence. Heterozygous NPHS2 variants may play a role in atypical cases with mild, late-onset course, and recurrence after transplantation

Understanding substance misuse amongst the mentally ill: an investigation of the context of, and motivations for, drug and alcohol use in an in-patient sample of individuals with psychotic illness

Background: Dual diagnosis (substance misuse and mental illness) is recognised as a significant clinical problem. However there is little evidence contributing to the understanding of what motivates people with psychotic illnesses to use drugs and alcohol, and in what social context. There is still less evidence concerning the correlates of dual diagnosis in in-patient settings including the relationship between mental health service settings and the initiation and maintenance of substance misuse. This study reports the prevalence, social context of, and motivations for substance use in a sample of in-patients with psychotic illnesses.;Methods and measures: Staff on 9 acute mental health wards and 2 psychiatric intensive care units in North London used a Clinician Drug and Alcohol Use Rating Scale to assess whether working age in-patients with psychotic illness also met the criteria for harmful alcohol or drug use, or dependence during the preceding six months. Those meeting the criteria for harmful use or dependence were then approached to participate in the study. Participants were interviewed and asked to report on the nature, extent, social context and attributions of their substance use, and whether they had continued to use whilst an in-patient. Measures used included an Inventory of Alcohol and Drug Use Situations, a Self-Medication Questionnaire, a demographic schedule and a structured set of questions concerning substance use history and it's relationship to mental health service settings.;Results: All working age adult in-patients (264) were screened for a current or recent substance use disorder. One hundred and twenty nine individuals met the study criteria (48.9%), whilst a further 39 (15%) had a substance use history, but no associated impairment of these, 102 agreed to take part in the study (response rate 79%). Those with dual diagnosis were younger on average and more likely to be male, than those with psychosis alone. The majority (76%) suffered from schizophrenia and were detained under the Mental Health Act (1983), with 19% being street homeless. A wide range of substances including opiates, stimulant substances and khat were used by participants, but alcohol, cannabis and cocaine (respectively) were the most frequently used substances. Eighty one percent of the participants reported using on the ward during their current admission, with almost half of the participants buying substances from other in-patients. Methods of using reflected the wide range of substance use reported, and included intravenous injection, chasing, and smoking. A third of participants reported feeling pressurised to buy, or use substances with other in-patients. For the majority substance use was clearly a social activity with three quarters of the participants reporting that they typically used or drank with others. Sixteen percent of the participants reported typically using with other mental health service users. Two principal components analyses of use situations and self medication data each revealed three factors, explaining 68% and 66% of the variance respectively. All factors had high mean scores, and elicited motivations for substance use. They were (use related to): negative personal and social states (48% variance), pleasant social conditions (13% variance), reward (7% variance), social interaction and boredom (41%) social acceptance (14% variance), and medication side effects (9% variance). An exploratory cluster analysis aimed at identifying sub-groups with distinctive patterns of motivations for use. Scores within clusters varied, with the membership of one cluster scoring highly on all factor items while other cluster members scored low on several items, clearly influencing their motivations for use. This exploratory analysis gives some indication that there are a number of distinctive patterns of use, including people who use in a wide range of situations with a variety of motivations, those who primarily use for relief of unpleasant feelings and social anxiety, and those whose use is predominantly social.;Conclusions: Substance misuse is a common problem in users of adult mental health services, and innovative solutions to understand and address these problems are needed. Although it was uncommon for individuals to directly medicate the symptoms of their illness with substances, their motivations for use reflected a range of social difficulties, isolation and other affective problems. Further investigation of demographic variables and substance use motivations in a larger sample may be an effective way of delineating sub groups with distinct motivations and of developing treatment strategies which take these motivations into account

Fluid circulation pattern inside La Soufrière volcano (Guadeloupe) inferred from combined electrical resistivity tomography, self-potential, soil temperature and diffuse degassing measurements

International audienceAfter a drastic decline in 1983, hydrothermal activity at La Soufrière lava dome (Guadeloupe, Lesser Antilles) has been progressively increasing in the summit area since 1992, raising the threat of a renewed eruptive activity. To better constrain the geometry of the hydrothermal system, an extensive high-resolution self-potential survey was performed on the dome and three multi-method profiles combining electrical resistivity tomography, self-potential, ground thermometry and soil CO 2 diffuse degassing measurements were carried out to cover its southern periphery in January 2011. Results indicate that hydrothermal ascending flows are currently restricted to a proximal area including the dome and its very vicinity. The extension of hydrothermal alteration inferred from electrical resistivity tomography reflects the presence of a heat source just below the dome. A first-order correction of topography-related self-potential variations allows the identification of major hydrothermal fluid circulations pathways, as well as significant meteoric infiltration zones. Local shifting of hydrothermal fluids towards the dome periphery is favored by the presence of major axes. The regional La Ty fault appears as the major axis draining large volumes of hydrothermal and magmatic fluids. However hydrothermal activity remains confined inside a collapse structure surrounding the dome, that formed in the last 9000 years as a result of recurrent edifice collapses, the latest occurring at the onset of the 1530 AD eruption. The combination of these qualitative results with structural analysis leads to a synthetic model of magmatic and hydrothermal fluids circulation inside the dome, which may be useful for the assessment of potential hazards associated with a renewal of fluid pres-surization, and a possibly associated partial flank-failure

Sliding motion of a bubble against an inclined wall from moderate to high bubble Reynolds number

The motion of a bubble sliding over an inclined wall from moderate to high bubble Reynolds number is studied experimentally for a wide range of liquid properties and bubbles sizes, considering wall inclination angles from nearly horizontal to nearly vertical. All experiments are restricted to sliding behavior, below the transition to steady bouncing motion. We study both the shape of the bubble and its drag coefficient. For small angles, the bubble shape is dominated by gravitational effects resulting in a flattened shape against the wall; for large angles, the bubble remains in constant contact with the wall but adopts a shape that is aligned perpendicularly to the wall, closer to that observed for an inertia- dominated free rising bubble. We model this transition of shape considering balances among surface tension, gravitational, and inertial forces; we observe good agreement with experiments. We found that the drag coefficient is strongly influenced by the shape that the bubble adopts as it slides over the wall. By considering the flow in the film and around the bubble, we propose a correlation to predict the drag coefficient for each regime of bubble shape. In the regime dominated by viscous effects, the drag of a single bubble is increased due to the mirror effect with the wall and by the friction in the film formed between the wall; conversely, for the case dominated by inertial effects, the drag coefficient is constant. The behavior for a single bubble is changed: no significant increase due to deformation. In both shape regimes the proposed expression agrees well with the experimental measurements