Field study of transit time through compacted clays : interim annual report

Interim annual report, July 1, 1989 to June 30, 1990Ope

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

Calibration test of PET scanners in a multi-centre clinical trial on breast cancer therapy monitoring using 18F-FLT.

UNLABELLED: A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results. MATERIAL AND METHODS: 11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated. RESULTS: There was no significant difference for dose calibrator measurements (median of difference -0.04%; min = -4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference -0.69%; min = -9.97%; max = +9.60%). CONCLUSION: No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems

PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.Peer reviewe

Relationship Between Osteonecrosis of the Jaw and Bisphosphonate Treatment

Terapija bisfosfonatima i njezina etiopatogenetska povezanost s aseptičkom osteonekrozom čeljusti važan je javnozdravstveni problem današnjice. Svrha je rada pregledom suvremene znanstvene literature utvrditi posljedice višestrukog djelovanja bisfosfonata (antiosteoklastična aktivnost, citotoksičnost na meka i koštana tkiva, antiangiogeneza, genski čimbenici, poremećena ravnoteža između osteoklasta i osteoblasta). Terapija bisfosfonatima jedan je od najčešćih uzroka razvoja osteonekroze čeljusti. Epidemiološki podaci pokazuju da se javlja u bolesnika koji su uzimali jedan ili kombinanciju nitrogenih bisfosfonata. Najvažniji čimbenici rizika za ovu nuspojavu su vrsta bisfosfonata (napose visokopotentni pamidronat i zoledronat koji se daju intravenski), njihova doza i duljina medikacije te vrsta bolesti zbog koje se propisuje terapija. Pojava osteonekroze čeljusti zabilježena je uglavnom u onkoloških bolesnika i u samo 5 % bolesnika s osteoporozom koji su liječeni bisfosfonatima. U patogenezi osteonekroze povezane s bisfosfonatima važno je, sa stajališta dentalnomedicinske prakse, dobro opće oralno zdravlje jer se osteonekroza javlja napose nakon prethodnoga parodontološkog i oralnokirurškog zahvata.Bisphosphonate treatment and its aetiopathogenic association with aseptic osteonecrosis of the jaw is one of the more prominent public health issues today. The aim of this review is to see into the mechanisms of bisphosphonate effects on bones described in literature (anti-osteoclastic activity, cytotoxicity, antiangiogenesis, genetic factors, and imbalance between osteoclasts and osteoblasts). Bisphosphonate treatment is the dominant cause of jaw necrosis. Epidemiological data show an exclusive incidence of osteonecrosis of the jaw in patients who took one or a combination of nitrogen-containing bisphosphonates. Risk factors vary by the bisphosphonate potency (particularly risky are the highly potent pamidronate and zoledronate, which are given intravenously), dosage, duration of treatment, and the illness. Jaw necrosis is most common in oncology patients, and only 5 % in patients with osteoporosis. From a dental-medical point of view, a good oral health is important because osteonecrosis often appears after a periodontal or oral surgical procedure