Age- and Concentration-Dependent Elimination Half-Life of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Seveso Children

OBJECTIVE: Pharmacokinetic and statistical analyses are reported to elucidate key variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in children and adolescents. DESIGN: We used blood concentrations to calculate TCDD elimination half-life. Variables examined by statistical analysis include age, latency from exposure, sex, TCDD concentration and quantity in the body, severity of chloracne response, body mass index, and body fat mass. PARTICIPANTS: Blood was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18 years of age at the time of a nearby trichlorophenol reactor explosion in July 1976. RESULTS: TCDD half-life in persons < 18 years of age averaged 1.6 years while those ≥18 years of age averaged 3.2 years. Half-life is strongly associated with age, showing a cohort average increase of 0.12 year half-life per year of age or time since exposure. A significant concentration-dependency is also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for children < 12 years of age and 700 ppt when including adults. Moderate correlations are also observed between half-life and body mass index, body fat mass, TCDD mass, and chloracne response. CONCLUSIONS: Children and adolescents have shorter TCDD half-lives and a slower rate of increase in half-life than adults, and this effect is augmented at higher body burdens. RELEVANCE: Modeling of TCDD blood concentrations or body burden in humans should take into account the markedly shorter elimination half-life observed in children and adolescents and concentration-dependent effects observed in persons > 400–700 ppt

Determinants of Functional Coupling between Astrocytes and Respiratory Neurons in the Pre-Bötzinger Complex

Respiratory neuronal network activity is thought to require efficient functioning of astrocytes. Here, we analyzed neuron-astrocyte communication in the pre-Bötzinger Complex (preBötC) of rhythmic slice preparations from neonatal mice. In astrocytes that exhibited rhythmic potassium fluxes and glutamate transporter currents, we did not find a translation of respiratory neuronal activity into phase-locked astroglial calcium signals. In up to 20% of astrocytes, 2-photon calcium imaging revealed spontaneous calcium fluctuations, although with no correlation to neuronal activity. Calcium signals could be elicited in preBötC astrocytes by metabotropic glutamate receptor activation or after inhibition of glial glutamate uptake. In the latter case, astrocyte calcium elevation preceded a surge of respiratory neuron discharge activity followed by network failure. We conclude that astrocytes do not exhibit respiratory-rhythmic calcium fluctuations when they are able to prevent synaptic glutamate accumulation. Calcium signaling is, however, observed when glutamate transport processes in astrocytes are suppressed or neuronal discharge activity is excessive

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Hereditary cataract in the Bengal cat in Poland

Background: This paper reports the significant prevalence of a presumed hereditary cataract in the Bengal cat breed in Poland. The nuclear part of the lens is affected and previous reports from Sweden and France for this type of feline cataract suggest that a recessive mode of inheritance is probably involved. Results: Presumed congenital or neonatal cataract involving the posterior nuclear part of each lens was initially diagnosed in a 12 month old male Bengal cat. As both parents and a sibling were also affected with cataract, a group of 18 related and 11 non-related cats was then subsequently examined. Eight related cats and one non- related cat were found to be similarly affected. A breed survey was then completed using an additional five centres across Poland and a further 190 related cats were examined. A total of 223 cats have been involved in this study, with 75 (33%) being affected with several types of cataract and 67 (30%) being specifically affected with the same or similar nuclear lesions. Eight cats (3.6%) presented with other cataract types and a prominence of the posterior lens suture lines was recorded in 65 cats unaffected with cataract (29%). There were no demonstrable vision problems. Neither age nor coat colour was significantly associated with the nuclear cataract, but the nuclear cataract group had a higher proportion of females than the unaffected group. Pedigree analysis has indicated probable inheritance as a recessive trait. Conclusions: These findings suggest that a presumably inherited nuclear cataract is present in the Bengal cat breed in Poland. It is considered to be either congenital or of very early onset, probably being inherited as a recessive trait. Although the lesion has no noticeable effect on vision, breeders in Poland and worldwide should be aware of the disease and clinical examination of young breeding stock prior to reproduction is advisable

Transient disruption of M1 during response planning impairs subsequent offline consolidation

Transcranial magnetic stimulation (TMS) was used to probe the involvement of the left primary motor cortex (M1) in the consolidation of a sequencing skill. In particular we asked: (1) if M1 is involved in consolidation of planning processes prior to response execution (2) whether movement preparation and movement execution can undergo consolidation independently and (3) whether sequence consolidation can occur in a stimulus specific manner. TMS was applied to left M1 while subjects prepared left hand sequential finger responses for three different movement sequences, presented in an interleaved fashion. Subjects also trained on three control sequences, where no TMS was applied. Disruption of subsequent consolidation was observed, but only for sequences where subjects had been exposed to TMS during training. Further, reduced consolidation was only observed for movement preparation, not movement execution. We conclude that left M1 is causally involved in the consolidation of effective response planning for left hand movements prior to response execution, and mediates consolidation in a sequence specific manner. These results provide important new insights into the role of M1 in sequential memory consolidation and sequence response planning

Tailored or Routine Addition of an Antireflux Fundoplication in Laparoscopic Large Hiatal Hernia Repair: A Comparative Cohort Study

Contains fulltext : 98394.pdf (publisher's version ) (Open Access)BACKGROUND: There is controversy about the tailored or routine addition of an antireflux fundoplication in large hiatal hernia (type II-IV) repair. We investigated the strategy of selective addition of a fundoplication in patients with a large hiatal hernia and concomitant gastroesophageal reflux disease. METHODS: Between 2002 and 2008, 60 patients with a large hiatal hernia were evaluated preoperatively and 12 months after surgery by reflux-related symptoms, upper endoscopy, and esophageal 24-h pH monitoring. In patients with preoperatively documented gastroesophageal reflux disease, an antireflux fundoplication was added during hiatal hernia repair. RESULTS: An antireflux procedure was added in 35 patients and 25 patients underwent hiatal hernia repair only. Preoperative symptoms were improved or resolved in 31 patients (88.6%) in the group who had fundoplication and in 20 patients (87.0%) in the group who did not have fundoplication. In patients with fundoplication, esophagitis was present in 6 patients (22.2%) after surgery and abnormal esophageal acid exposure persisted in 11 (39.3%). Seven patients (38.9%) with hernia repair only developed abnormal esophageal acid exposure, and esophagitis was postoperatively generated in five (27.8%). In neither group did patients have new onset of daily heartburn or dysphagia. CONCLUSIONS: In patients with a large hiatal hernia associated with gastroesophageal reflux disease, addition of a fundoplication during hernia repair yields acceptable reduction of symptoms and does not generate symptomatic side effects. Objective control of reflux, however, is only moderate. Omission of an antireflux procedure in the absence of gastroesophageal reflux disease induced esophagitis in 28% and abnormal esophageal acid exposure in 39% of patients. Therefore, routine addition of an antireflux fundoplication should be recommended

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration