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Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there are few reports about their use in clinical practice. Which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared with those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalisable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These data should provide a basis for more informed counselling and clinical decision making.

We demonstrate theoretically the electric tunability due to the coalescence of exceptional points in PT-symmetric waveguides bounded by imperfect conductive layers. Owing to the competition effect of multimode interaction, multiple exceptional points and PT phase transitions could be attained in such a simple system, and their occurrences are strongly dependent on the boundary conductive layers. When the conductive layers become very thin, it is found that the oblique transmittance and reflectance of the same system can be tuned between zero and one by a small change in the carrier density. The results may provide an effective method for fast tuning and modulation of optical signals through electrical gating.

This study was a randomised controlled trial designed to assess the effectiveness of progressive muscle relaxation training (PMRT) in the clinical management of chemotherapy-related nausea and vomiting as an adjuvant intervention to accompany pharmacological antiemetic treatment (metoclopramide and dexamethasone i.v.). Seventy-one chemotherapy-naive breast cancer patients of an outpatient oncology unit of a university hospital in Hong Kong participated, with 38 subjects randomised to the experimental group and 33 to the control group. The intervention included the use of PMRT 1 h before chemotherapy was administered and daily thereafter for another 5 days (for a total of six PMRT sessions). Each session lasted for 25 min and was followed by 5 min of imagery techniques. The instruments used for data collection included the Chinese versions of the Profile of Mood States and the State-Trait Anxiety Inventory (measured before chemotherapy and then at day 7 and day 14 after chemotherapy), and the Morrow Assessment of Nausea and Vomiting Scale, which was used daily for the first 7 post-chemotherapy days. The use of PMRT considerably decreased the duration of nausea and vomiting in the experimental group compared with the control group (P<0.05), whereas there were trends toward a lower frequency of nausea and vomiting (P=0.07 and P=0.08 respectively). Neither nausea nor vomiting differed in intensity between the two groups. The significant effects were mainly evident on the first 4 post-chemotherapy days, when differences were statistically significant. Although there was a significantly less severe overall mood disturbance in the experimental group over time (P<0.05), this did not apply in the case of anxiety. Such findings suggest that PMRT is a useful adjuvant technique to complement antiemetics for chemotherapy-induced nausea and vomiting and that incorporation of such interventions in the care plan can enhance the standards of care of cancer patients who experience side effects of chemotherapy.

A prospective longitudinal study was designed to assess the role of pretreatment proneness to nausea and vomiting (NV) in the development of postchemotherapy NV in a group of Chinese breast cancer patients receiving moderately highly emetogenic chemotherapy. Seventy-one chemotherapy-naive subjects participated in the study. Patients were assessed the day before chemotherapy with measurements of their anxiety level, depression, fatigue and proneness to NV, motion sickness, NV experienced in past pregnancies, history of labyrinthitis, expectation of developing NV and expectation of developing pain. Patients also completed daily assessments of frequency, duration and intensity of NV for the 7 days after chemotherapy. Regression analyses revealed that nonpharmacological factors explained part of the variance of NV, the most common predictors being a history of labyrinthitis, expectation of developing NV after chemotherapy, younger age, stage of disease, and state anxiety. The explanatory power of the models ranged from 6% to 23% of the variance of the independent variable. There were different explanatory models for acute and delayed NV. Results indicate that consideration of the role of nonpharmacological factors in the development of NV could lead to more effective management of NV induced by chemotherapy.

New failure analysis results of miniaturized multilayer ceramic capacitors (sizes 0402, 0603, 0805 and 1206) which have been subjected to various degrees of thermal shock up to 450°C by ice-water or dry ice quenching are reported. The thermal shock resistance of 0402 multilayer ceramic capacitors was found to be about 400°C and considerably better than those of the larger ones. Microstructural and layer-by-layer insulation resistance analyses have clearly identified the physical locations responsible for the electrical leakage of defective capacitors. Further, no evidence of silver migration as a dominant failure mechanism has been observed for any of the defective capacitors under usual operating stresses. Comparisons ofI–V characteristics for multilayer ceramic capacitors quenched by ice-water and dry ice confirm that water plays a significant role in causing electrical failure at nominal bias. Comparisons with results obtained from practical surface mount printed circuit board assembly of mobile telephones is discussed. From these, failure mechanisms are proposed to explain the failure of miniaturized multilayer ceramic capacitors under normal service conditions.

Pigs with two mutant epitopes, Lpb5 of apolipoprotein B (apoB) and Lpu1 of a yet undefined apolipoprotein, specified by a haplotype Lpb5-Lpu1 and fed a cholesterol-free low fat diet show hypercholesterolemia. The purpose of this study was to establish whether a direct relationship exists between the swine lipoprotein concentration/composition and the genotype for the Lpb5-Lpu1 haplotype; i.e., homozygote versus heterozygote. Lipoproteins of fasted plasma from hypercholesterolemic swine, homozygous (HmHC) and heterozygous (HtHC) for Lpb5-Lpu1, and from normolipidemic (NL) pigs of other Lpb-Lpu haplotypes were separated into five layers by density gradient ultracentrifugation. Layer 1 contained particles of d less than 1.019 g/ml and layer 5 particles of d greater than 1.073 g/ml. Layers 2, 3, and 4 represented subfractions of low density lipoproteins (LDL). The plasma total cholesterol (TC) of the HmHC group (300 +/- 84 mg/dl) was different (P less than 0.05) from the HtHC group (200 +/- 80 mg/dl) and in both HmHC and HtHC, TC was significantly higher (P less than 0.0005 and P less than 0.005, respectively) than that of the NL group (69 +/- 14 mg/dl). The elevation in plasma TC was due to the increased TC in layers 2 and 3: a 13- and 7-fold increase in HmHC and a 7- and 4-fold increase in HtHC in layers 2 and 3, respectively. Parallel increases in unesterified cholesterol were observed in these two layers. Marked increases in apoB were also observed in layers 2 and 3 of HmHC and intermediate increases in apoB in the same two layers of HtHC.(ABSTRACT TRUNCATED AT 250 WORDS)

The enzyme disaggregatase (Dag) from Methanosarcina mazei was studied immunochemically. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified Dag under reducing and nonreducing conditions revealed a single band with a 94-kDa molecular mass. Dag was found to be immunogenic in rabbits; a polyclonal antibody probe was prepared and used to detect the enzyme by slide immunoenzymatic assay, immunofluorescence, and immunoblotting in various species of Methanosarcina known to convert from packets to single cells, including M. mazei. The enzyme could not be detected in other members of the family Methanosarcinaceae that do not convert. By immunogold electron microscopy, Dag was mapped to the cell wall of packets and to the cell membrane of single cells of two M. mazei strains.

Annexins are structurally related proteins that bind phospholipids in a Ca2(+)-dependent manner and possess at least four conserved 70-amino acid repeat domains. The ability of certain annexins to promote contact between vesicle membranes in vitro has prompted the suggestion that these proteins regulate membrane traffic in exocytosis. We have previously found that annexins I and II promote contact between vesicles whereas annexin V does not. In order to understand the mechanism of annexin I-mediated vesicle-vesicle contact, we prepared a monoclonal antibody that specifically inhibits annexin I-mediated vesicle aggregation. We identified the domain of annexin I recognized by this monoclonal antibody by using it to screen an expression library containing random fragments of annexin I cDNA. The antibody identified a fragment encoding amino acids 41-118 (the first repeat plus 8 residues of the amino-terminal tail). We constructed a chimeric protein containing these amino acids of annexin I fused to the second, third, and fourth repeats of annexin V. Transfer of this domain conferred the ability to promote vesicle aggregation, confirming that this domain participates directly in mediating contact between vesicle membranes.

We report here a case of fatal Penicillium citrinum infection. The patient, who suffered from acute myeloid leukemia, developed signs and symptoms typical of fungal pneumonia and pericardial tamponade after undergoing standard induction chemotherapy. Despite attaining complete remission of her leukemia, the patient succumbed 8 weeks after presentation. At autopsy, multiple nodular cavitary pulmonary lesions with invasion by fungal hyphae were found. Pericardial and lung tissue obtained at autopsy grew P. citrinum, a fungus ubiquitous in the environment but seldom reported as a pathogen. The microbiological findings were consistent with the histopathological features and confirmed this as a case of true P. citrinum infection causing fatal pulmonary and pericardial complications in an immunocompromised host.