Using graphical probability analysis (Bayes Nets) to evaluate a conditional DNA inclusion

This paper discusses the analysis of cases in which the inclusion or exclusion of a particular suspect, as a possible contributor to a DNA mixture, depends on the value of a variable (the number of contributors) that cannot be determined with certainty. It offers alternative ways to deal with such cases, including sensitivity analysis and object-oriented Bayesian networks, that separate uncertainty about the inclusion of the suspect from uncertainty about other variables. The paper presents a case study in which the value of DNA evidence varies radically depending on the number of contributors to a DNA mixture: if there are two contributors, the suspect is excluded; if there are three or more, the suspect is included; but the number of contributors cannot be determined with certainty. It shows how an object-oriented Bayesian network can accommodate and integrate varying perspectives on the unknown variable and how it can reduce the potential for bias by directing attention to relevant considerations and distinguishing different sources of uncertainty. It also discusses the challenge of presenting such evidence to lay audiences.

Arterial hypertension after surgical closure of omphalocele and gastroschisis.

Arterial hypertension has been reported as a complication of surgical closure of an abdominal wall defect. No report studying the incidence, the characteristics and the clinical significance of hypertension after surgical correction of an omphalocele or gastroschisis has been published so far. The medical records of all newborns with surgically corrected gastroschisis or omphalocele identified in two centers were retrospectively evaluated. Arterial hypertension was defined as a mean daily systolic and/or diastolic blood pressure value higher than the 95 percentile for age and/or weight, according to literature data. The timing of surgery, weight gain, plasma creatinine and the use of diuretics or vasoactive drugs were compared between the groups with and without hypertension. Seventy-two patients were identified and included in the study, 29 with omphalocele and 43 with gastroschisis. Those with omphalocele were born at a mean age of 37.3+/-2.6 weeks with a mean birth weight of 2,971+/-715 g, and those with gastroschisis were born at 36.1+/-2.0 weeks with a mean birth weight of 2,527+/-498 g. Blood pressure values of 66 patients were available for analysis. Of the omphalocele patients, 46.2% (12/26) developed systolic hypertension, compared to 17.5% (7/40) of the patients with gastroschisis (P =0.024). Hypertension was always transient, lasting an average of 4 and 1 day in the omphalocele and gastroschisis groups, respectively. Two patients with omphalocele were given anti-hypertensive therapy. There was no difference between patients with or without hypertension regarding weight gain, use of vasoactive drugs or diuretics, mean weekly creatinine values or the timing of surgery. Newborns with an abdominal wall defect frequently present with transient arterial hypertension. Hypertension occurs significantly more often, is more severe and lasts longer in patients with omphalocele than in patients with gastroschisis. In both groups, hypertension is transient and rarely requires therapy. The cause of hypertension remains unclear.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.

Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology.

The ability to express tightly controlled amounts of endogenous and recombinant proteins in plant cells is an essential tool for research and biotechnology. Here, the inducibility of the soybean heat-shock Gmhsp17.3B promoter was addressed in the moss Physcomitrella patens, using beta-glucuronidase (GUS) and an F-actin marker (GFP-talin) as reporter proteins. In stably transformed moss lines, Gmhsp17.3B-driven GUS expression was extremely low at 25 degrees C. In contrast, a short non-damaging heat-treatment at 38 degrees C rapidly induced reporter expression over three orders of magnitude, enabling GUS accumulation and the labelling of F-actin cytoskeleton in all cell types and tissues. Induction levels were tightly proportional to the temperature and duration of the heat treatment, allowing fine-tuning of protein expression. Repeated heating/cooling cycles led to the massive GUS accumulation, up to 2.3% of the total soluble proteins. The anti-inflammatory drug acetyl salicylic acid (ASA) and the membrane-fluidiser benzyl alcohol (BA) also induced GUS expression at 25 degrees C, allowing the production of recombinant proteins without heat-treatment. The Gmhsp17.3B promoter thus provides a reliable versatile conditional promoter for the controlled expression of recombinant proteins in the moss P. patens.

Closure of the Monte Carlo dynamical equation in the spherical Sherrington-Kirkpatrick model

We study the analytical solution of the Monte Carlo dynamics in the spherical Sherrington-Kirkpatrick model using the technique of the generating function. Explicit solutions for one-time observables (like the energy) and two-time observables (like the correlation and response function) are obtained. We show that the crucial quantity which governs the dynamics is the acceptance rate. At zero temperature, an adiabatic approximation reveals that the relaxational behavior of the model corresponds to that of a single harmonic oscillator with an effective renormalized mass.

Department of Human Services Proposal for State Mental Health Institute Closure and Consolidation, December 15, 2009

The Department’s recommendation for closure and consolidation is based on an analysis of the existing programs, persons served, physical plant costs, expenses and renovation/infrastructure costs for relocation, and review of the draft report from the MHI Task Force. Further detail surrounding the analysis used to drive the recommendation is found under the Recommendations section, beginning on page 12 of this report. In response to the legislative requirement to recommend closure and consolidation of an MHI, the Department recommends the closure of the Mount Pleasant Mental Health Institute with consolidation of its programs and operational beds at the Independence Mental Health Institute. With this recommendation, Independence MHI will add beds to accommodate the 15 adult psychiatric beds, 14 dual diagnosis beds, and 50 substance abuse treatment beds now located at the Mount Pleasant MHI. This relocation will take an estimated six months from the time statutory authority and corresponding appropriations are received.

Essays on the treatment of cash flows under stochastic interest rates

Abstract This paper shows how to calculate recursively the moments of the accumulated and discounted value of cash flows when the instantaneous rates of return follow a conditional ARMA process with normally distributed innovations. We investigate various moment based approaches to approximate the distribution of the accumulated value of cash flows and we assess their performance through stochastic Monte-Carlo simulations. We discuss the potential use in insurance and especially in the context of Asset-Liability Management of pension funds.

Bilateral anterior pubic osteotomy in bladder exstrophy closure.

PURPOSE: We report our clinical experience with anterior pelvic osteotomy in 16 patients who underwent surgery for bladder exstrophy. The technique and its difficulties are discussed. MATERIALS AND METHODS: Anterior pelvic osteotomy of the superior ramus of the public bone is a simple and efficient method to facilitate symphyseal approximation and abdominal wall closure without or with low tension on the suture lines in neonates who undergo surgery for bladder exstrophy. Older children in whom surgery has been delayed can also benefit from this method. Compared to other methods of osteotomy in exstrophy surgery it does not require additional incisions, nor does the patient need to be repositioned on the operating table. A successful operation does not depend on any particular orthopedic skills and it can easily be done by the pediatric urologist. RESULTS: Immediate postoperative results regarding abdominal wall closure were excellent in all 16 patients. However, major postoperative complications developed in 2 patients. Despite antibiotic prophylaxis a severe soft tissue infection developed in 1 child, resulting in complete bladder dehiscence. In another patient an obturator nerve injury resulted in transient palsy, which resolved completely. While the first complication was not related to osteotomy, the second was osteotomy related. CONCLUSIONS: Bilateral superior ramotomy of the pubic bones is a new alternative, easily performed technique to optimize bladder exstrophy surgery in children.

Premature epiphyseal closure in an adolescent treated by retinoids for acne: An unusual cause of anterior knee pain

Introduction.- Retinoids are effective and widely used for the treatment of severe acne. Their use can be, however, associated with numerous side effects. For example, some rare cases of premature epiphyseal closure were reported.Observation.- A sixteen-year-old soccer player consulted for bilateral progressive anterior knee pain, since two months, evoking a femoro-patellar origin. After physiotherapy, the pain decreases on the right but remained on the left. The history taking brought out the use of isotretinoin for more than 6 months (0.5 mg/kg). Magnetic resonance imaging (MRI) findings showed an irregularity of the growth plate and an important metaphyso-epiphyseal oedema, more marked on the left. The diagnosis of retinoid induced premature ephysieal closure was retained. The treatment was stopped, with a resolution of symptoms within two months. The control MRI of the left knee present persisting small sequelar thumbprint-like growth plate lesion. Eighteen months later, neither limb-length discrepancy nor static disorder was noticed.Discussion.- Premature epiphyseal closure is a rare complication of retinoid treatment of acne. Retinoids induce an invasion of the growth plate by osteoclasts and a decrease in proteoglycans synthesis. The knee seems the most involved joint. The clinical presentation is aspecific, sometimes lightly symptomatic. A careful pharmacological history and an appropriate imaging are necessary. MRI is now the gold standard. It shows an irregularity of the growth plate with an oedema on both sides. In chronic phase, a thumbprint-like image may persist. The symptoms resolution arises in few weeks after the treatment interruption. A single case of static disorder was reported until now. The small size of the growth plate interruptions, insufficient to lead to a growth disorder if the medicament is stopped early enough, explains probably it. This complication being rare, a radiological follow-up of the young patients treated by retinoids is not proposed.

Conditional manipulation of sex ratios by ant workers: A test of kin selection theory

Variable queen mating frequencies provide a unique opportunity to study the resolution of worker-queen conflict over sex ratio in social Hymenoptera, because the conflict is maximal in colonies headed by a singly mated queen and is weak or nonexistent in colonies headed by a multiply mated queen. In the wood ant Formica exsecta, workers in colonies with a singly mated queen, but not those in colonies with a multiply mated queen, altered the sex ratio of queen-laid eggs by eliminating males to preferentially raise queens. By this conditional response to queen mating frequency, workers enhance their inclusive fitness.