Characterization and Assessment of a Novel Plate and Frame MD Module for Single Pass Wastewater Concentration-FEED Gap Air Gap Membrane Distillation.

Membrane distillation (MD) is an up and coming technology for concentration and separation on the verge of reaching commercialization. One of the remaining boundaries is the lack of available full-scale MD modules and systems suitable to meet the requirements of potential industrial applications. In this work a new type of feed gap air gap MD (FGAGMD) plate and frame module is introduced, designed and characterized with tap water and NaCl-H2O solution. The main feature of the new channel configuration is the separation of the heating and cooling channel from the feed channel, enabling a very high recovery ratio in a single pass. Key performance indicators (KPIs) such as flux, gained output ratio (GOR), recovery ratio and thermal efficiency are used to analyze the performance of the novel module concept within this work. A recovery rate of 93% was reached with tap water and between 53%-32% with salt solutions ranging between 117 and 214 g NaCl/kg solution with this particular prototype module. Other than recovery ratio, the KPIs of the FGAGMD are similar to those of an air gap membrane distillation (AGMD) channel configuration. From the experimental results, furthermore, a new MD KPI was defined as the ratio of heating and cooling flow to feed flow. This RF ratio can be used for optimization of the module design and efficiency.

Incorporating non-equilibrium dynamics into demographic history inferences of a migratory marine species.

Understanding how dispersal and gene flow link geographically separated the populations over evolutionary history is challenging, particularly in migratory marine species. In southern right whales (SRWs, Eubalaena australis), patterns of genetic diversity are likely influenced by the glacial climate cycle and recent history of whaling. Here we use a dataset of mitochondrial DNA (mtDNA) sequences (n = 1327) and nuclear markers (17 microsatellite loci, n = 222) from major wintering grounds to investigate circumpolar population structure, historical demography and effective population size. Analyses of nuclear genetic variation identify two population clusters that correspond to the South Atlantic and Indo-Pacific ocean basins that have similar effective breeder estimates. In contrast, all wintering grounds show significant differentiation for mtDNA, but no sex-biased dispersal was detected using the microsatellite genotypes. An approximate Bayesian computation (ABC) approach with microsatellite markers compared the scenarios with gene flow through time, or isolation and secondary contact between ocean basins, while modelling declines in abundance linked to whaling. Secondary-contact scenarios yield the highest posterior probabilities, implying that populations in different ocean basins were largely isolated and came into secondary contact within the last 25,000 years, but the role of whaling in changes in genetic diversity and gene flow over recent generations could not be resolved. We hypothesise that these findings are driven by factors that promote isolation, such as female philopatry, and factors that could promote dispersal, such as oceanographic changes. These findings highlight the application of ABC approaches to infer the connectivity in mobile species with complex population histories and, currently, low levels of differentiation.

Exposure to Mycobacterium avium decreases the protective effect of the DNA vaccine pVAXhsp65 against Mycobacterium tuberculosis-induced inflammation of the pulmonary parenchyma.

This work investigated the effect of previous Mycobacterium avium exposure on the protective ability of the DNA vaccine pVAXhsp65 against inflammation in the pulmonary parenchyma. BALB/c mice were presensitized with heat-killed M. avium and then immunized with three doses of pVAXhsp65 prior to challenge with Mycobacterium tuberculosis. M. avium sensitization induced high levels of spontaneous IL-5 production that were concomitant with a positive delayed-type hypersensitivity reaction; antigen-specific IFN-γ production was also observed upon splenocyte stimulation. Prior exposure to M. avium resulted in altered cytokine and antibody production induced by immunization with pVAXhsp65; instead of a Th1 response, vaccinated mice previously exposed to M. avium developed a strong Th2 response. This switch to a Th2 response coincided with the loss of the anti-inflammatory effect of pVAXhsp65 vaccination previously observed in the pulmonary parenchyma of mice infected with M. tuberculosis. These results suggest that exposure to environmental mycobacteria can modulate immune responses induced by mycobacterial vaccines other than bacillus Calmette-Guérin.

Limbic encephalitis in children and adolescents.

OBJECTIVE: Limbic encephalitis is rare in people <18 years of age and rarely given a formal diagnosis. DESIGN: Retrospective study on presentation and outcome of children and adolescents with the clinico-radiological syndrome of limbic encephalitis tested for specific neuronal autoantibodies (Abs) over 3.5 years. SETTING: Assessment, diagnosis, treatment and follow-up at 12 neuropaediatric and neurological departments in Europe, with Abs determined in Bonn, Germany and Oxford, UK. PATIENTS: Ten patients <18 years of age who presented with a disorder mainly affecting the limbic areas of <5 years' duration with MRI evidence of mediotemporal encephalitis (hyperintense T2/FLAIR signal, resolving over time). RESULTS: Median age at disease onset was 14 years (range 3-17). Eight patients had defined Abs: one each with Hu or Ma1/2 Abs, four with high titre glutamic acid decarboxylase (GAD) Abs, two of whom had low voltage-gated potassium channel (VGKC) Abs and two with only low titre VGKC Abs. A tumour was only found in the patient with Hu Abs (a neuroblastoma). After a median follow-up of 15 months with corticosteroid or intravenous immunoglobulin treatment, starting after a median of 4 months, two patients recovered, eight remained impaired and one died. CONCLUSIONS: Limbic encephalitis is a disease that can occur in childhood or adolescence with many of the hallmarks of the adult disorder, suggesting that both result from similar pathogenic processes. Since most of the cases were non-paraneoplastic, as now also recognised in adults, more systematic and aggressive immunotherapies should be evaluated in order to improve outcomes.

Neonatal BCG immunization followed by DNAhsp65 boosters: highly immunogenic but not protective against tuberculosis - a paradoxical effect of the vector?

A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis.

Topiramate in the treatment of highly refractory patients with Dravet syndrome.

The purpose of this study was to assess the effectiveness and tolerability of topiramate (TPM) as add-on therapy in children with Dravet syndrome and considered unsatisfactorily controlled using stiripentol. All the 36 patients having been treated with TPM in our centre in 2001 were retrospectively evaluated. Seventy percent of them still received stiripentol when TPM was introduced. The association of both drugs did not need any particular adaptation of dosages. The mean TPM follow-up was 13.3 months (4-25 months) and the mean optimal TPM dose was 3.2 mg/kg/d (0.6-9.2 mg/kg/d). Twenty eight children (78 %) showed more than 50 % reduction in the frequency of generalized tonic-clonic seizures and status epilepticus (SE), whereas 8 % had more than 50 % increase. Six patients (17 %) remained seizure-free for at least 4 months. The most frequently reported side-effects were gastrointestinal and behavioural disturbances. TPM had to be stopped in 17 % of patients, because of poor tolerability and/or lack of efficacy. Topiramate seems therefore to be helpful in Dravet syndrome, even in patients not satisfactorily controlled by stiripentol. Both drugs can be easily and safely associated.

Effects of eccentric versus concentric training on thigh muscle strength and EMG.

The purpose of this study was to compare pure eccentric and concentric strength training regarding possible specific effects of muscle action type on neuromuscular parameters, such as a decreased inhibition during maximal voluntary eccentric actions. Two groups of young healthy adult men performed 10 weeks of either eccentric or concentric unilateral isokinetic knee extensor training at 90 degrees.s(-1), 4 sets of 10 maximal efforts, 3 days a week. Knee extensor torque and surface EMG from the quadriceps and hamstring muscle groups were collected and quantified in a window between 30 and 70 degrees knee angle (range of motion 90-5 degrees ) during maximal voluntary eccentric and concentric knee extensor actions at 30, 90, and 270 degrees.s(-1). Changes in strength of the trained legs revealed more signs of specificity related to velocity and contraction type after eccentric than concentric training. No major training effects were present in eccentric to concentric ratios of agonist EMG or in relative antagonist (hamstring) activation. Thus, for the trained leg, the muscle action type and speed specific changes in maximal voluntary eccentric strength could not be related to any effects on neural mechanisms, such as a selective increase in muscle activation during eccentric actions. Interestingly, with both types of training there were specific cross-education effects, that is, action type and velocity specific increases in strength occurred in the contralateral, untrained, leg, accompanied by a specific increase in eccentric to concentric EMG ratio after eccentric training.

Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy.

BACKGROUND: We recently reported a mutation in the PRKAG2 gene to be responsible for a familial syndrome of ventricular preexcitation, atrial fibrillation, conduction defects, and cardiac hypertrophy. We now report a novel mutation in PRKAG2 causing Wolff-Parkinson-White syndrome and conduction system disease with onset in childhood and the absence of cardiac hypertrophy. METHODS AND RESULTS: DNA was extracted from white blood cells obtained from family members. PRKAG2 exons were amplified by polymerase chain reaction and were screened for mutations by direct sequencing. The genomic organization of the PRKAG2 gene was determined using inter-exon long-range polymerase chain reaction for cDNA sequence not available in the genome database. A missense mutation, Arg531Gly, was identified in all affected individuals but was absent in 150 unrelated individuals. The PRKAG2 gene was determined to consist of 16 exons and is at least 280 kb in size. CONCLUSIONS: We identified a novel mutation (Arg531Gly) in the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase (AMPK) to be responsible for a syndrome associated with ventricular preexcitation and early onset of atrial fibrillation and conduction disease. These observations confirm an important functional role of AMPK in the regulation of ion channels specific to cardiac tissue. The identification of the cardiac ion channel(s) serving as substrate for AMPK not only would provide insight into the molecular basis of atrial fibrillation and heart block but also may suggest targets for the development of more specific therapy for these common rhythm disturbances.

Elevated rates of nonsynonymous substitution in island birds.

Slightly deleterious mutations are expected to fix at relatively higher rates in small populations than in large populations. Support for this prediction of the nearly-neutral theory of molecular evolution comes from many cases in which lineages inferred to differ in long-term average population size have different rates of nonsynonymous substitution. However, in most of these cases, the lineages differ in many other ways as well, leaving open the possibility that some factor other than population size might have caused the difference in substitution rates. We compared synonymous and nonsynonymous substitutions in the mitochondrial cyt b and ND2 genes of nine closely related island and mainland lineages of ducks and doves. We assumed that island taxa had smaller average population sizes than those of their mainland sister taxa for most of the time since they were established. In all nine cases, more nonsynonymous substitutions occurred on the island branch, but synonymous substitutions showed no significant bias. As in previous comparisons of this kind, the lineages with smaller populations might differ in other respects that tend to increase rates of nonsynonymous substitution, but here such differences are expected to be slight owing to the relatively recent origins of the island taxa. An examination of changes to apparently "preferred" and "unpreferred" synonymous codons revealed no consistent difference between island and mainland lineages.

Current status of the implantable cardioverter-defibrillator.

Clinical trials have established the superiority of the implantable cardioverter-defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden cardiac death and in high-risk patients with coronary artery disease. The ICD has evolved to overcome the limitation of earlier devices that required thoracotomy for implantation and were fraught with inappropriate shock delivery. Current ICDs are implanted in a similar manner to cardiac pacemakers and incorporate sophisticated rhythm-discrimination algorithms to prevent inappropriate therapy. Managing the patient with an ICD requires an understanding of the multiprogrammable features of modern devices. Drug interactions and potential sources of electromagnetic interference may adversely affect ICD function. Driving restrictions may be necessary under certain conditions. The cost-effectiveness of ICD therapy appears favorable, given the marked survival benefit seen in randomized trials relative to antiarrhythmic drug treatment. The growing number of ICD recipients necessitates an understanding of the specialized features of the modern ICD and the role of device therapy in clinical practice.

Evolution of odorant receptors expressed in mammalian testes.

About 10% of mammalian odorant receptors are transcribed in testes, and odorant-receptor proteins have been detected on mature spermatozoa. Testis-expressed odorant receptors (TORs) are hypothesized to play roles in sperm chemotaxis, but they might also be ordinary nasal odorant receptors (NORs) that are expressed gratuitously in testes. Under the sperm-chemotaxis hypothesis, TORs should be subject to intense sexual selection and therefore should show higher rates of amino acid substitution than NORs, but under the gratuitous-expression hypothesis, TORs are misidentified NORs and therefore should evolve like other NORs. To test these predictions, we estimated synonymous and nonsynonymous divergences of orthologous NOR and TOR coding sequences from rat and mouse. Contrary to both hypotheses, TORs are on average more highly conserved than NORs, especially in certain domains of the OR protein. This pattern suggests that some TORs might perform internal nonolfactory functions in testes; for example, they might participate in the regulation of sperm development. However, the pattern is also consistent with a modified gratuitous-expression model in which NORs with specialized ligand specificities are both more highly conserved than typical NORs and more likely to be expressed in testes.

Diagnosis and management of inadvertently placed pacing and ICD leads in the left ventricle: a multicenter experience and review of the literature.

Three patients from different centers with pacemaker or ICD leads endocardially implanted in the left ventricle are described. All leads, two ventricular pacing leads and one ICD lead, were inserted through a patent foramen ovale or an atrial septum defect. The diagnosis was made 9 months, 14 months, and 16 years, respectively, after implantation. All patients had right bundle branch block configuration during ventricular pacing. Chest X ray was suggestive of a left-sided positioned lead except in the ICD patient. Diagnosis was confirmed with echocardiography in all patients. One patient with a ventricular pacing lead presented with a transient ischemic attack at 1-month postimplantation. During surgical repair of the atrial septum defect 14 months later, the lead was extracted and thrombus was attached to the lead despite therapy with aspirin. The other patients were asymptomatic without anticoagulation (9 months and 16 years after implant). No thrombus was present on the ICD lead at the time of the cardiac transplantation in one patient. We reviewed 27 patients with permanent leads described in the literature. Ten patients experienced thromboembolic complications, including three of ten patients on antiplatelet therapy. The lead was removed in six patients, anticoagulation with warfarin was effective for secondary prevention in the four remaining patients. In the asymptomatic patients, the lead was removed in five patients. In the remaining patients, 1 patient was on warfarin, 2 were on antiplatelet therapy, and in 3 patients the medication was unknown. After malposition was diagnosed, three additional patients were treated with warfarin. In conclusion, if timely removal of a malpositioned lead in the left ventricle is not preformed, lifelong anticoagulation with warfarin can be recommended as the first choice therapy and lead extraction reserved in case of failure or during concomitant surgery.

Electrically evoked eccentric and concentric torque-velocity relationships in human knee extensor muscles.

The torque-velocity relationship, obtained during in situ conditions in humans, demonstrates a levelling-off of eccentric torque output at the isometric torque level, at least for knee extensor actions. In contrast, the in vitro force-velocity relationship for animal muscle preparations is characterized by a sharp rise in eccentric force from isometric maximum. A force-regulating 'protective' mechanism has been suggested during maximal voluntary high-tension eccentric muscle actions. To investigate this phenomenon, maximal voluntary and three different levels of submaximal, electrically induced torques were compared during isometric and low velocity (10, 20 and 30 degrees s-1) isokinetic eccentric and concentric knee extensor actions in 10 healthy, moderately trained subjects. Eccentric torque was higher than isometric during electrically evoked, but not during maximal voluntary muscle actions. In contrast, concentric torque was significantly lower than isometric for both maximal voluntary and submaximal, electrically evoked conditions. Comparisons of normalized torques (isometric value under each condition set to 100%) demonstrated that the maximal voluntary eccentric torque had to be increased by 20%, and the isometric by 10% in order for the maximal voluntary torque-velocity curve to coincide with the electrically stimulated submaximal ones. These results support the notion that a tension-regulating mechanism is present primarily during eccentric maximal voluntary knee extensor actions.

Muscle strength and electromyogram in boys and girls followed through puberty.

The main purpose of this study was to investigate the changes in anthropometric measures and muscle strength that occur during puberty in children from the age of 11 to 16 years. Special attention was paid to possible gender- and muscle action-type-specific alterations in torque/velocity and EMG/velocity characteristics. Sixteen children participated in the study (9 boys and 7 girls). Eccentric and concentric muscle strength was measured on an isokinetic dynamometer at angular velocities of 45, 90 and 180 degrees x s(-1). Simultaneously, a surface electromyogram (EMG) was recorded from the quadriceps muscle. At the age of 11, the boys and girls exhibited equal anthropometric measures and strength performance. In both genders, body measures and muscle strength increased significantly during the 5-year period, with larger increases being recorded for the boys. In addition, the boys increased selectively their eccentric torque per body mass, indicating an action-type-specific change in muscle quality. The general shape of the torque/velocity relationship exhibited an adult-like pattern both before and after puberty, and did not differ between genders. Both pre- and postpuberty, myoelectric activity was generally lower during eccentric than concentric actions, the highest values occurring for both genders in the concentric 180 degrees x s(-1) test. Ratios of eccentric to concentric torque per EMG, which reflect electromechanical efficiency, showed no significant changes with age. A significant velocity- and gender-specific change in electromechanical efficiency was observed at the highest speed at postpuberty, where the ratio for the girls was higher than for the boys.

Quantifying driver stress: developing a system for collecting and processing bio-metric signals in natural situations.

A system for quantifying the physiological features of emotional stress is being developed for use during a driving task. Two prototypes, using sensors that measure the driver's skin conductance, respiration, muscle activity, and heart activity are presented. The first system allows sampling rates of 200 Hz on two fast channels and 20 Hz on six additional channels. It uses a wearable computer to do real-time processing on the signals and has an attached digital camera which was used to capture images of the driver's facial expression once every minute. The second system uses a car-based computer that allows a sampling rate of 1984 samples per second on eight channels. This system uses multiple video cameras to continuously capture the driver's facial expression and road conditions. The data is then synchronized with the physiological signals using a video quad-splitter. The methods for extracting physiological features in the driving environment are discussed, including measurement of the skin conductance orienting response, muscle activity, pulse, and respiration patterns. Preliminary studies show how using multiple modalities of sensors can help discriminate reactions to driving events and how individual's response to similar driving conditions can vary from day to day.

Specific effects of eccentric and concentric training on muscle strength and morphology in humans.

The purpose of this study was to compare pure eccentric and concentric isokinetic training with respect to their possible specificity in the adaptation of strength and morphology of the knee extensor muscles. Ten moderately trained male physical education students were divided into groups undertaking eccentric (ETG) and concentric (CTG) training. They performed 10 weeks of maximal isokinetic (90 degrees x s(-1)) training of the left leg, 4x10 repetitions - three times a week, followed by a second 10-week period of similar training of the right-leg. Mean eccentric and concentric peak torques increased by 18% and 2% for ETG and by 10% and 14% for CTG, respectively. The highest increase in peak torque occurred in the eccentric 90 degrees x s(-1) test for ETG (35%) whereas in CTG strength gains ranged 8%-15% at velocities equal or lower than the training velocity. Significant increases in strength were observed in the untrained contra-lateral leg only at the velocity and mode used in ipsilateral training. Cross-sectional area of the quadriceps muscle increased 3%-4% with training in both groups, reaching statistical significance only in ETG. No major changes in muscle fibre composition or areas were detected in biopsies from the vastus lateralis muscle for either leg or training group. In conclusion, effects of eccentric training on muscle strength appeared to be more mode and speed specific than corresponding concentric training. Only minor adaptations in gross muscle morphology indicated that other factors, such as changes in neural activation patterns, were causing the specific training-induced gains in muscle strength.

Selection on the protein-coding genes of the TBE1 family of transposable elements in the ciliates Oxytricha fallax and O. trifallax.

TBE1s are "cut-and-paste" transposable elements found in high copy number in the germline genomes of the ciliates Oxytricha fallax and O. trifallax. TBE1 "family" sequence (sequence of mixed polymerase chain reaction products generated using primers that match roughly half the TBE1s in host whole-cell DNA) was obtained from both host species. Although family sequence autoradiograms represent thousands of different elements, they are as legible as those representing corresponding sequences of a single TBE1, implying that ideal polymorphisms are rare within the genes examined. Nucleotide polymorphisms among TBE1s (indicated by ambiguities in family sequence) are far more common at third than at first or second positions of codons of genes, implying that selection has conserved the amino acid sequences of these genes in the majority of TBE1s. Portions of the transposase gene and another TBE1 gene have been sequenced from 10 individual TBE1s. None of these portions is interrupted by stop codons or frameshifts, and, for both genes, pairwise comparisons of these sequences show that nonsynonymous differences are significantly less common than synonymous differences, again implicating conservative selection Phylogenetic analysis shows that multiple divergent lineages of TBE1s have evolved under this selection within O. fallax. All these results are unexpected for cut-and-paste transposons in eukaryotic hosts: since transposase encoded by intact elements presumably acts in trans, it can duplicate mutant copies (those that do not encode functional transposase) found in the same genome, and thus no selection is expected to maintain the transposase gene. The selection demonstrated here could act at transposition (if functional TBE1s are preferentially transposed) or at the level of the host (if the host's fitness depends on functional TBE1 genes). TBE1-encoded proteins might be responsible for the precise excision of TBE1s that occurs during development of the host somatic nucleus; selection on hosts for uninterrupted somatic genes would then translate into selection for TBE1 protein-coding competence. We suggest a method for distinguishing between these two classes of explanations by finding and analyzing divergent alleles of ancestral transposable element insertions.