Explore the vast range of titles available.

Background: Myoclonus-dystonia (M-D) is a movement disorder with autosomal dominant inheritance and reduced penetrance but may also occur sporadically. Recently, mutations in the epsilon-sarcoglycan gene (SGCE) were shown to cause M-D. Furthermore, single variants in the dopamine D2 receptor (DRD2) and DYT1 genes were found in combination with SGCE mutations in two M-D families, and another M-D locus was recently mapped to chromosome 18p11 in one family. Methods: The authors clinically and genetically characterised ten consecutive cases with myoclonus-dystonia; seven familial and three sporadic. Twenty nine M-D patients and 40 unaffected family members underwent a standardised clinical examination by a movement disorder specialist. Index cases were screened for mutations in the SGCE, DYT1, and DRD2 genes and for deletions of the SGCE gene. Suitable mutation negative families were tested for linkage to the SGCE region and to chromosome 18p11. Results: Two SGCE mutations were detected among the seven familial but no mutation in the sporadic cases. Haplotype analysis at the new M-D locus was compatible with linkage in two families and excluded in another family, suggesting at least one additional M-D gene. There were no obvious clinical differences between M-D families with and without detected mutations. Conclusion: M-D is genetically heterogeneous with SGCE mutations accounting for the disease in only part of the clinically typical cases.

Is there such a thing as a distinctive Jewish literature? While definitions have been offered, none has been universally accepted. Modern Jewish literature lacks the basic markers of national literatures: it has neither a common geography nor a shared language-though works in Hebrew or Yiddish are almost certainly included-and the field is so diverse that it cannot be contained within the bounds of one literary category. Each of the fifteen essays collected inModern Jewish Literaturestakes on the above question by describing a movement across boundaries-between languages, cultures, genres, or spaces. Works in Hebrew and Yiddish are amply represented, but works in English, French, German, Italian, Ladino, and Russian are also considered. Topics range from the poetry of the Israeli nationalist Natan Alterman to the Russian poet Osip Mandelstam; from turn-of-the-century Ottoman Jewish journalism to wire-recorded Holocaust testimonies; from the intellectual salons of late eighteenth-century Berlin to the shelves of a Jewish bookstore in twentieth-century Los Angeles. The literary world described inModern Jewish Literaturesis demarcated chronologically by the Enlightenment, the Haskalah, and the French Revolution, on one end, and the fiftieth anniversary of the State of Israel on the other. The particular terms of the encounter between a Jewish past and present for modern Jews has varied greatly, by continent, country, or village, by language, and by social standing, among other things. What unites the subjects of these studies is not a common ethnic, religious, or cultural history but rather a shared endeavor to use literary production and writing in general as the laboratory in which to explore and represent Jewish experience in the modern world.

Rapid onset dystonia-parkinsonism (RDP) is a rare movement disorder with autosomal dominant inheritance, characterised by sudden onset of dystonic spasms and slowness of movement. To date, three families have been described that share linkage to the same location on chromosome 19q13, designated DYT12. Very recently, mutations in the ATP1A3 gene at the DYT12 locus have been demonstrated in seven unrelated patients, including the three previously linked families. A large RDP family is reported here, with eight definitely and one possibly affected members, that is not linked to the DYT12 region and has no mutation in the ATP1A3 gene. Predominant cranial-cervical involvement of dystonia occurred in this family, which has also been described in patients with idiopathic torsion dystonia linked to the DYT6 region on chromosome 8 and is a rare finding in DYT1 dystonia. Molecular genetic analysis also excluded linkage to the DYT6 locus and the GAG deletion in DYT1, suggesting at least one additional RDP gene.

A locus for juvenile onset open angle glaucoma (OAG) has been assigned to chromosome 1q in families with autosomal dominant inheritance (GLC1A), due to mutations in the TIGR/MYOC gene. For adult onset OAG, called primary open angle glaucoma or POAG, five loci have so far been mapped to different chromosomes (GLC1B-GLC1F). Except for the GLC1B locus, the other POAG loci have so far been reported only in single large pedigrees. We studied a large family identified in Epirus, Greece, segregating POAG in an autosomal dominant fashion. Clinical findings included increased cup to disc ratio (mean 0.7), characteristic glaucomatous changes in the visual field, and intraocular pressure before treatment more than 21 mmHg (mean 31 mmHg), with age at diagnosis 33 years and older. Linkage analysis was performed between the disease phenotype and microsatellite DNA polymorphisms. Linkage was established with a group of DNA markers located on chromosome 3q, where the GLC1C locus has previously been described in one large Oregon pedigree. A maximal multipoint lod score of 3.88 was obtained at marker D3S1763 (penetrance 80%). This represents the second POAG family linked to the GLC1C locus on chromosome 3q, and haplotype analysis in the two families suggests an independent origin of the genetic defect.

An assessment of the pattern of change in height, weight and subscapular skinfold thickness is made on the basis of a sample of children, 6-15 years of age, from the northern Italian city of Aosta. Simple examination of mean values across ages suggests that the timing of salient changes in the three growth variables is quite similar. The temporal pattern of change among obese individuals is comparable to that for normals, although the magnitude of change is greater among the obese. Trends in the variance of height and weight (corrected for height) across ages attest to a noticeable decline in the uniformity of the growth pattern during puberty. Geographic origin of parents appears to make a significant contribution to differences in height and weight among individuals in this sample. Namely, children whose parents were born in southern Italy tend to be shorter and heavier for the same height than those whose parents originated in northern Italy.

We investigated the ultrafast structural dynamics of cyclobutanone following photoexcitation at \\(\\lambda=200\\) nm using gas-phase megaelectronvolt ultrafast electron diffraction. Our investigation complements the simulation studies of the same process within this special issue. It provides information about both electronic state population and structural dynamics through well-separable inelastic and elastic electron scattering signatures. We observe the depopulation of the photoexcited S\\(_2\\) state of cyclobutanone with n3s Rydberg character through its inelastic electron scattering signature with a time constant of \\((0.29 \\pm 0.2)\\) ps towards the S\\(_1\\) state. The S\\(_1\\) state population undergoes ring-opening via a Norrish Type-I reaction, likely while passing through a conical intersection with S\\(_0\\). The corresponding structural changes can be tracked by elastic electron scattering signatures. These changes appear with a delay of \\((0.14 \\pm 0.05)\\) ps with respect the initial photoexcitation, which is less than the S\\(_2\\) depopulation time constant. This behavior provides evidence for the ballistic nature of the ring-opening once the S\\(_1\\) state is reached. The resulting biradical species react further within \\((1.2 \\pm 0.2)\\) ps via two rival fragmentation channels yielding ketene and ethylene, or propene and carbon monoxide. Our study showcases both the value of gas-phase ultrafast diffraction studies as an experimental benchmark for nonadiabatic dynamics simulation methods and the limits in the interpretation of such experimental data without comparison to such simulations.

I am happily in a position to give you an ocular demonstration of the action of tuberculin on tubercular tissue.

In a phase 3 trial, participants with early Alzheimer’s disease who received the monoclonal antibody lecanemab had less decline on measures of cognition and function at 18 months than those who received placebo.

As people, animals and materials are transported across increasingly large distances in a globalized world, threats to our biosecurity and food security are rising. Aotearoa New Zealand is an island nation with many endemic species, a strong local agricultural industry, and a need to protect these from pest threats, as well as the economy from fraudulent commodities. Mitigation of such threats is much more effective if their origins and pathways for entry are understood. We propose that this may be addressed in Aotearoa using strontium isotope analysis of both pests and products. Bioavailable radiogenic isotopes of strontium are ubiquitous markers of provenance that are increasingly used to trace the origin of animals and plants as well as products, but currently a baseline map across Aotearoa is lacking, preventing use of this technique. Here, we have improved an existing methodology to develop a regional bioavailable strontium isoscape using the best available geospatial datasets for Aotearoa. The isoscape explains 53% of the variation (R² = 0.53 and RMSE = 0.00098) across the region, for which the primary drivers are the underlying geology, soil pH, and aerosol deposition (dust and sea salt). We tested the potential of this model to determine the origin of cow milk produced across Aotearoa. Predictions for cow milk (n = 33) highlighted all potential origin locations that share similar ⁸⁷Sr/⁸⁶Sr values, with the closest predictions averaging 7.05 km away from their true place of origin. These results demonstrate that this bioavailable strontium isoscape is effective for tracing locally produced agricultural products in Aotearoa. Accordingly, it could be used to certify the origin of Aotearoa’s products, while also helping to determine if new pest detections were of locally breeding populations or not, or to raise awareness of imported illegal agricultural products.

Reirradiation is a widely accepted option for second-line treatment in patients with recurrent glioma. However, no standard radiation regimen has been defined. Hypofractionation is aimed at reducing patients' burden while maintaining the survival benefit, but may increase the risk of radionecrosis. The primary objective of this study is to determine if reirradiation in just 4 fractions is non-inferior to 10 fractions, regarding survival after reirradiation. RISING trial A was an open label, randomized, non-inferiority, phase III trial with 1:1 allocation for 130 patients among all participating centers but failed to recruit according to planning. RISING trial B will be a phase II, multi-center, clinical trial with a historic control group. The experimental group receives 4 stereotactic fractions. The historic control group has received 10 fractions (standard-of-care) with a biologically equivalent dose on surrounding brain tissue. The primary endpoint is overall survival after reirradiation. The key secondary endpoint is progression-free survival. Other secondary endpoints are recurrence patterns, toxicity (specifically clinically relevant radionecrosis) and anti-edema treatment. We will collect and report on Health-Related Quality of Life (HRQoL) data in the experimental arm. We expect to demonstrate the non-inferiority and safety of a 4-fraction hypofractionation schedule for reirradiation of gliomas. This schedule may then become a standard-of-care option with minimal burden for patients with recurrent glioma, and limited use of scarce healthcare resources. Registered at Netherlands Trial Register (NTR), Trial ID: NL72766.041.20, registered at 07-04-2020, https://www.onderzoekmetmensen.nl/en/trial/52643.