Limits on Momentum-Dependent Asymmetric Dark Matter with CRESST-II.

The usual assumption in direct dark matter searches is to consider only the spin-dependent or spin-independent scattering of dark matter particles. However, especially in models with light dark matter particles O(GeV/c^{2}), operators which carry additional powers of the momentum transfer q^{2} can become dominant. One such model based on asymmetric dark matter has been invoked to overcome discrepancies in helioseismology and an indication was found for a particle with a preferred mass of 3 GeV/c^{2} and a cross section of 10^{-37} cm^{2}. Recent data from the CRESST-II experiment, which uses cryogenic detectors based on CaWO_{4} to search for nuclear recoils induced by dark matter particles, are used to constrain these momentum-dependent models. The low energy threshold of 307 eV for nuclear recoils of the detector used, allows us to rule out the proposed best fit value above.

[Transoral approach for sublingual-plunging ranula]. / Transoraler Zugang bei sublingualer Tauchranula.

The case of a 7-year-old boy suffering from progressive submental/submandibular swelling is reported. Following clinical and imaging diagnostics (MRI), the suspected diagnosis of a sublingual-plunging ranula was made. Surgery was performed with transoral excision of the sublingual gland in combination with excision of the ranula. Additional submandibular gland excision should be avoided.

Towards an automated data cleaning with deep learning in CRESST.

The CRESST experiment employs cryogenic calorimeters for the sensitive measurement of nuclear recoils induced by dark matter particles. The recorded signals need to undergo a careful cleaning process to avoid wrongly reconstructed recoil energies caused by pile-up and read-out artefacts. We frame this process as a time series classification task and propose to automate it with neural networks. With a data set of over one million labeled records from 68 detectors, recorded between 2013 and 2019 by CRESST, we test the capability of four commonly used neural network architectures to learn the data cleaning task. Our best performing model achieves a balanced accuracy of 0.932 on our test set. We show on an exemplary detector that about half of the wrongly predicted events are in fact wrongly labeled events, and a large share of the remaining ones have a context-dependent ground truth. We furthermore evaluate the recall and selectivity of our classifiers with simulated data. The results confirm that the trained classifiers are well suited for the data cleaning task.

Secular equilibrium assessment in a CaWO4 target crystal from the dark matter experiment CRESST using Bayesian likelihood normalisation.

CRESST is a leading direct detection sub-GeVc-2 dark matter experiment. During its second phase, cryogenic bolometers were used to detect nuclear recoils off the CaWO4 target crystal nuclei. The previously established electromagnetic background model relies on Secular Equilibrium (SE) assumptions. In this work, a validation of SE is attempted by comparing two likelihood-based normalisation results using a recently developed spectral template normalisation method based on Bayesian likelihood. Albeit we find deviations from SE in some cases we conclude that these deviations are artefacts of the fit and that the assumptions of SE is physically meaningful.

Simulation-based design study for the passive shielding of the COSINUS dark matter experiment.

The COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) experiment aims at the detection of dark matter-induced recoils in sodium iodide (NaI) crystals operated as scintillating cryogenic calorimeters. The detection of both scintillation light and phonons allows performing an event-by-event signal to background discrimination, thus enhancing the sensitivity of the experiment. The choice of using NaI crystals is motivated by the goal of probing the long-standing DAMA/LIBRA results using the same target material. The construction of the experimental facility is foreseen to start by 2021 at the INFN Gran Sasso National Laboratory (LNGS) in Italy. It consists of a cryostat housing the target crystals shielded from the external radioactivity by a water tank acting, at the same time, as an active veto against cosmic ray-induced events. Taking into account both environmental radioactivity and intrinsic contamination of materials used for cryostat, shielding and infrastructure, we performed a careful background budget estimation. The goal is to evaluate the number of events that could mimic or interfere with signal detection while optimising the geometry of the experimental setup. In this paper we present the results of the detailed Monte Carlo simulations we performed, together with the final design of the setup that minimises the residual amount of background particles reaching the detector volume.

Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.

BACKGROUND: Deletions in the 17p13.3 region are associated with abnormal neuronal migration. Point mutations or deletion copy number variants of the PAFAH1B1 gene in this genomic region cause lissencephaly, whereas extended deletions involving both PAFAH1B1 and YWHAE result in Miller-Dieker syndrome characterised by facial dysmorphisms and a more severe grade of lissencephaly. The phenotypic consequences of YWHAE deletion without deletion of PAFAH1B1 have not been studied systematically. METHODS: We performed a detailed clinical and molecular characterization of five patients with deletions involving YWHAE but not PAFAH1B1, two with deletion including PAFAH1B1 but not YWHAE, and one with deletion of YWHAE and mosaic for deletion of PAFAH1B1. RESULTS: Three deletions were terminal whereas five were interstitial. Patients with deletions including YWHAE but not PAFAH1B1 presented with significant growth restriction, cognitive impairment, shared craniofacial features, and variable structural abnormalities of the brain. Growth restriction was not observed in one patient with deletion of YWHAE and TUSC5, implying that other genes in the region may have a role in regulation of growth with CRK being the most likely candidate. Using array based comparative genomic hybridisation and long range polymerase chain reaction, we have delineated the breakpoints of these nonrecurrent deletions and show that the interstitial genomic rearrangements are likely generated by diverse mechanisms, including the recently described Fork Stalling and Template Switching (FoSTeS)/Microhomology Mediated Break Induced Replication (MMBIR). CONCLUSIONS: Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. The interstitial deletions are mediated by diverse molecular mechanisms.

Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3.

DFNB3, a locus for nonsyndromic sensorineural recessive deafness, maps to a 3-centimorgan interval on human chromosome 17p11.2, a region that shows conserved synteny with mouse shaker-2. A human unconventional myosin gene, MYO15, was identified by combining functional and positional cloning approaches in searching for shaker-2 and DFNB3. MYO15 has at least 50 exons spanning 36 kilobases. Sequence analyses of these exons in affected individuals from three unrelated DFNB3 families revealed two missense mutations and one nonsense mutation that cosegregated with congenital recessive deafness.

Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene.

The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea.

Geant4-based electromagnetic background model for the CRESST dark matter experiment.

The CRESST (Cryogenic Rare Event Search with Superconducting Thermometers) dark matter search experiment aims for the detection of dark matter particles via elastic scattering off nuclei in CaWO 4 crystals. To understand the CRESST electromagnetic background due to the bulk contamination in the employed materials, a model based on Monte Carlo simulations was developed using the Geant4 simulation toolkit. The results of the simulation are applied to the TUM40 detector module of CRESST-II phase 2. We are able to explain up to ( 68 ± 16 ) % of the electromagnetic background in the energy range between 1 and 40 keV .

Do we intervene inappropriately for ST elevation?

ST elevation on a 12 lead ECG is one of the cardinal features of acute myocardial infarction (AMI), yet it also occurs with other clinical conditions such as spontaneous pneumothorax. Three cases are presented, all of whom had chest pain and ST elevation. All had pneumothoraces yet only one had an AMI. Thrombolysis was administered to one patient. With the current pressure on "door-to-needle" times, emergency physicians should take care to differentiate between these entities.

Current concepts in salvage procedures for failing microvascular flaps: is there a superior technique? Insights from a systematic review of the literature.

Microvascular free tissue transfer is a routine procedure with high predictability and a low complication rate. However, compromised flap perfusion remains a challenge and there is no consensus regarding the appropriate flap salvage protocol. The purpose of this study was to identify techniques with implications for flap salvage procedures and to assess their efficacy. A systematic review of studies published in the literature between 1990 and 2015, with predefined inclusion and exclusion criteria, was performed. The data obtained were pooled and analyzed. A total of 39 studies qualified for data extraction. The overall level of evidence was low and the total number of reported cases was limited (330 flaps). Five studies involved control groups and supplied comparative data. Surgical anastomotic revision and thrombectomy are inevitable in every flap salvage protocol. Four techniques or combinations of these with positive effects on flap salvage success rates were identified: thrombectomy with a Fogarty catheter (six studies, 68 flaps), intraoperative use of thrombolytic drugs (16 studies, 184 flaps), placement of an arteriovenous fistula (five case reports, five flaps), and the postoperative application of medicinal leeches (11 studies, 73 flaps). Currently available data exploring flap salvage procedures are limited. None of the techniques presented yielded superior salvage outcomes.

Calorie restriction for treatment of gestational diabetes.

Birth weights of infants of 35 gestational diabetic mothers treated with calorie restriction alone (1200-1800 kcal) were compared with those of infants of 2337 nondiabetic women, including two control groups (A and B) matched for race, body mass index, age, and parity. All women were screened for gestational diabetes with the O'Sullivan screening method, and a 3-h oral glucose tolerance test was performed on all abnormal results. Control group A mothers had a normal screen, and control group B mothers had an abnormal screen with a normal glucose tolerance test. Pregnancy weight gain was significantly less for the gestational diabetic mothers (mean +/- SD 4.6 +/- 4.9 kg) than for the general prenatal population (9.3 +/- 5.3 kg), group A control subjects (9.7 +/- 5.3 kg), and group B control subjects (9.7 +/- 5.4 kg; P less than 0.0005). No infant of a gestational diabetic mother was below the 10th percentile for weight, and birth weights were similar to those of the control groups even though weight gain after the 28th wk of gestation was only 1.7 +/- 1.6 kg. The frequency of macrosomia (birth weight greater than or equal to 4000 g) was similar among the gestational diabetic mothers (9.3%), the general prenatal population (7.4%), and group A mothers (11.6%) but significantly higher for the group B control subjects (20.9%; chi 2 = 8.57, P less than 0.005). This study demonstrated that gestational diabetic mothers who are calorie restricted have infants with normal birth weights and a frequency of macrosomia less than that of screen-positive nondiabetic women with similar macrosomic risk factors.

Characterisation and genetic mapping of a new X linked deafness syndrome.

BACKGROUND: Hereditary forms of hearing loss are classified as syndromic, when deafness is associated with other clinical features, or non-syndromic, when deafness occurs without other clinical features. Many types of syndromic deafness have been described, some of which have been mapped to specific chromosomal regions. METHODS: Here we describe a family with progressive sensorineural hearing loss, cognitive impairment, facial dysmorphism, and variable other features, transmitted by apparent X linked recessive inheritance. Haplotype analysis of PCR products spanning the X chromosome and direct sequencing of candidate genes were used to begin characterising the molecular basis of features transmitted in this family. Comparison to known syndromes involving deafness, mental retardation, facial dysmorphism, and other clinical features was performed by review of published reports and personal discussions. RESULTS: Genetic mapping places the candidate locus for this syndrome within a 48 cM region on Xq1-21. Candidate genes including COL4A5, DIAPH, and POU3F4 were excluded by clinical and molecular analyses. CONCLUSIONS: The constellation of clinical findings in this family (deafness, cognitive impairment, facial dysmorphism, variable renal and genitourinary abnormalities, and late onset pancytopenia), along with a shared haplotype on Xq1-21, suggests that this represents a new form of syndromic deafness. We discuss our findings in comparison to several other syndromic and non-syndromic deafness loci that have been mapped to the X chromosome.

Magnetic resonance imaging: a useful tool to distinguish between keratocystic odontogenic tumours and odontogenic cysts.

In contrast to odontogenic cysts, keratocystic odontogenic tumours often recur and require more aggressive surgical treatment, so we tried to find features that distinguished between them on magnetic resonance imaging (MRI). Without knowing the diagnosis, two radiologists reviewed intensity (low, intermediate, or high) and homogeneity (homogeneous or heterogeneous) of signals in short-tau-inversion-recovery (STIR), T1- and T2-weighted, and fat-suppressed, contrast-enhanced MRI in 20 consecutive patients with oval, radiolucent lesions of the mandible on panoramic radiography, and who were subsequently confirmed histopathologically to have either an odontogenic cyst or a keratocystic odontogenic tumour (n=10 in each group). Fisher's exact test was statistically significant at p<0.05. Delineation of a contrast-enhanced wall of a cyst with high signal intensity distinguished odontogenic cysts (9/10 and 8/10, respectively) from keratocystic odontogenic tumours (3/10, p=0.02, and 1/10, p=0.01, respectively). One radiologist found odontogenic cysts were more likely to be homogeneous on unenhanced T1-weighted images (odontogenic cysts 9/10, keratocystic odontogenic tumours 3/10, p=0.02) and one on contrast-enhanced MRI, when the cyst wall was enhanced (odontogenic cysts 7/9, keratocystic odontogenic tumours 0/3, p=0.01). There were no other significant distinguishing features on MRI. In conclusion, the signal intensity of the enhanced wall seems to be a feature on contrast-enhanced MRI that differentiates odontogenic cysts from keratocystic odontogenic tumours.

De novo deletions and duplications of 17q25.3 cause susceptibility to cardiovascular malformations.

BACKGROUND: Genomic disorders resulting from deletion or duplication of genomic segments are known to be an important cause of cardiovascular malformations (CVMs). In our previous study, we identified a unique individual with a de novo 17q25.3 deletion from a study of 714 individuals with CVM. METHODS: To understand the contribution of this locus to cardiac malformations, we reviewed the data on 60,000 samples submitted for array comparative genomic hybridization (CGH) studies to Medical Genetics Laboratories at Baylor College of Medicine, and ascertained seven individuals with segmental aneusomy of 17q25. We validated our findings by studying another individual with a de novo submicroscopic deletion of this region from Cytogenetics Laboratory at Cincinnati Children's Hospital. Using bioinformatic analyses including protein-protein interaction network, human tissue expression patterns, haploinsufficiency scores, and other annotation systems, including a training set of 251 genes known to be linked to human cardiac disease, we constructed a pathogenicity score for cardiac phenotype for each of the 57 genes within the terminal 2.0 Mb of 17q25.3. RESULTS: We found relatively high penetrance of cardiovascular defects (~60 %) with five deletions and three duplications, observed in eight unrelated individuals. Distinct cardiac phenotypes were present in four of these subjects with non-recurrent de novo deletions (range 0.08 Mb-1.4 Mb) in the subtelomeric region of 17q25.3. These included coarctation of the aorta (CoA), total anomalous pulmonary venous return (TAPVR), ventricular septal defect (VSD) and atrial septal defect (ASD). Amongst the three individuals with variable size duplications of this region, one had patent ductus arteriosus (PDA) at 8 months of age. CONCLUSION: The distinct cardiac lesions observed in the affected patients and the bioinformatics analyses suggest that multiple genes may be plausible drivers of the cardiac phenotype within this gene-rich critical interval of 17q25.3.

The role of mouse mutants in the identification of human hereditary hearing loss genes.

The mouse is the model organism for the study of hearing loss in mammals. In recent years, the identification of five different mutated genes in the mouse (Pax3, Mitf; Myo7a, Pou4f3, and Myo15) has led directly to the identification of mutations in families with either congenital sensorineural deafness or progressive sensorineural hearing loss. Each of these cases is reviewed here. In addition to providing a powerful gateway to the identification of human hearing loss genes, the study of mouse deafness mutants can lead to the discovery of critical components of the auditory system. Given the availability of several mouse mutants that affect possible homologues of other human deafness genes, it is likely that the mouse will play a key role in identifying other human hearing loss genes in the years to come.

Are there characteristic alterations in lung tissue associated with Crohn's disease?

Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D-glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis.

How should HMOs measure their efforts and accomplishments?

Accounting procedures among prepaid healthcare plans vary considerably, so much so that the accounting profession is considering what should be appropriate practice. Some standardarization is needed because of wide variations in measuring performance. This can be an obstacle in discussions of whether HMOs are more efficient than other delivery systems and what type of HMO is most successful. Healthcare expenses can be recognized at the time of payment, at the time they are reported to the plan, at the time services are provided, or in anticipation of future services. The accounting profession has identified four HMO models to determine whether organizational structure should affect financial reporting. The models, which differ in the relationship between the HMO and enrolled members and physicians, are staff model, group model, individual practice association, and network model. The accountants reject recognizing expense at the time of payment because it does not conform to generally accepted accounting principles. They suggest two alternatives: recognizing expense when the service is provided, or recognizing as expense, on the date of initial service, the expected cost of all anticipated services required by the diagnosis. The former approach appears preferable because of its consistency with the way healthcare services are delivered and the logic of accounting theory.

Similarity measure for quality control of dental CAD/CAM-applications.

There is no measure for morphometric quality control of dental CAD/CAM-restorations as well as for evaluation of newly developed CAD/CAM-applications. The aim of this study was to (a) establish a 3D-measure for morphological comparisons, (b) to proof its metrical and subjective-visual validity and (c) to explore morphological features which have relevant impact on visual perception. 125 maxillary anterior teeth were chosen from a digital library of 3D data sets and compared by automatic superimposition with a best-fit method. The superimposition was analyzed by a newly defined 3-dimensional similarity measure, called shape similarity value (SSV). With this measure, similarity between symmetrical and non-symmetrical teeth was evaluated and the metrical validity was tested. Additionally, visual evaluation of tooth similarities were performed and analyzed by means of multivariate statistical procedures, to test the correspondence between metrical similarity measure and visual similarity perception. The measure clearly reproduced the similarity of contralateral teeth and the dissimilarity of teeth between different individuals. The coincidence between quantitative similarity measure and visual perception was moderate. In conclusion, the presented 3D-measure can be considered as a first substantial step towards a morphometric quality control of CAD/CAM-restorations of anterior teeth.