Improved Neutron Lifetime Measurement with UCNτ.

We report an improved measurement of the free neutron lifetime τ_{n} using the UCNτ apparatus at the Los Alamos Neutron Science Center. We count a total of approximately 38×10^{6} surviving ultracold neutrons (UCNs) after storing in UCNτ's magnetogravitational trap over two data acquisition campaigns in 2017 and 2018. We extract τ_{n} from three blinded, independent analyses by both pairing long and short storage time runs to find a set of replicate τ_{n} measurements and by performing a global likelihood fit to all data while self-consistently incorporating the ß-decay lifetime. Both techniques achieve consistent results and find a value τ_{n}=877.75±0.28_{stat}+0.22/-0.16_{syst} s. With this sensitivity, neutron lifetime experiments now directly address the impact of recent refinements in our understanding of the standard model for neutron decay.

Increased risk of incident osteoporosis and osteoporotic fracture in tuberculosis patients: a population-based study in a tuberculosis-endemic area.

The occurrence of osteoporosis in tuberculosis, a chronic infection, has rarely been evaluated. In this study, we found significantly higher incidence rates of osteoporosis (Adjusted hazard ratio (AHR) 1.82) and osteoporotic fracture (AHR 2.33) in tuberculosis patients than matched cohorts, which suggest that osteoporosis screening should be considered in tuberculosis patients' follow-up program. The aim of this study is to determine the occurrence of incident osteoporosis in patients who completed anti-tuberculosis (TB) treatment. INTRODUCTION: Chronic inflammatory disorders are associated with an increased risk of osteoporosis. Although TB is an infectious disease characterized by systemic inflammatory responses, the impact of active TB on incident osteoporosis is unclear. We used the Taiwan National Health Insurance Research Database to investigate the association between history of active TB and incident osteoporosis and osteoporotic fracture. METHODS: In this nationwide retrospective cohort study, active TB patients and their age- and sex-matched controls were identified from the National Health Insurance Research Database in Taiwan during 2000-2012. The occurrence of incident osteoporosis, osteoporotic fractures, and risk factors associated with osteoporosis among TB patients and matched controls were analyzed. RESULTS: We observed incident osteoporosis in 2.2% (n = 86) of the TB patients and in 1.1% (n = 162) of the matched controls. The incidence rate of osteoporosis was 4.31 and 1.80 per 1000 person-years, which was significantly higher in TB patients (p < 0.001). In multivariate analysis, TB was an independent risk factor for osteoporosis. The other independent factors associated with osteoporosis were older age, female sex, chronic obstructive pulmonary disease, asthma, and lower income. Moreover, we demonstrated that the occurrence of osteoporotic fracture was significantly higher in TB patients. CONCLUSIONS: Patients with a history of active TB have a higher incidence rate of osteoporosis and osteoporotic fracture.

Determinants of mortality in elderly patients with tuberculosis: a population-based follow-up study.

Elderly individuals with tuberculosis (TB) are more likely to have a non-specific clinical presentation of TB and high mortality. However, factors associated with mortality in elderly TB patients have not been extensively studied. This retrospective cohort study aimed to identify factors associated with death among elderly Taiwanese with TB. All elderly patients with TB from 2006 to 2014 in Taipei, Taiwan, were included in a study. Multiple logistic regression was used to identify the factors associated with death in elderly TB patients. The mean age of the 5011 patients was 79·7 years; 74·1% were men; 32·7% had mortality during the study follow-up period. After controlling for potential confounders, age ⩾75 years (reference: 65-74 years), male sex, end-stage renal disease (ESRD), malignancy, acid-fast bacilli-smear positivity, TB-culture positivity, pleural effusion on chest radiograph and notification by an ordinary ward or intensive care unit were associated with a higher risk of all-cause death; while high school, and university or higher education, cavity on chest radiograph and directly observed therapy were associated with a lower risk of all-cause death. This study found that the proportion of death among elderly patients with TB in Taipei, Taiwan, was high. To improve TB treatment outcomes, future control programmes should particularly target individuals with comorbidities (e.g. ESRD and malignancy) and those with a lower socio-economic status (e.g. not educated).

Increased risk of pulmonary tuberculosis in patients with gastroesophageal reflux disease.

BACKGROUND: Previous studies have suggested a close correlation between gastroesophageal reflux disease (GERD) and various respiratory disorders. However, the association between GERD and tuberculosis (TB) remains unexplored. METHODS: Using data retrieved from Taiwan's National Health Insurance Research Database from 2000 to 2009, this longitudinal nationwide cohort study included a total of 63,930 patients with GERD and controls matched by age, sex and comorbidities. Risk factors associated with the development of pulmonary TB (PTB) were investigated. RESULTS: Active PTB was documented in 65 (0.20%) patients with GERD and 41 (0.13%) matched cohorts within 1 year of GERD diagnosis. The incidence rate of PTB in the GERD group and the matched cohort was respectively 24.1 and 15.2 cases per 10,000 person-years. In multivariate analysis, GERD was an independent risk factor for PTB (adjusted HR 1.63, 95%CI 1.10-2.40, P = 0.015). Among patients with GERD, independent predictors for PTB included older age, male sex, chronic obstructive pulmonary disease, asthma and exposure to proton pump inhibitors (PPIs). CONCLUSION: Patients with GERD have a significantly increased risk of PTB within 1 year of GERD diagnosis. Exposure to PPIs is an independent predictor for PTB among patients with GERD.

HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese.

PURPOSE: HLA-B*15:02 screening is recommended before starting carbamazepine in Han Chinese and Southeast Asians because the allele is strongly predictive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) induced by the drug. We examined whether other HLA-B alleles are also involved and whether the association extends to other antiepileptic drugs (AEDs). METHODS: Cases of SJS/TEN induced by any AEDs were recruited and matched (1:5) with AED-tolerant controls. Carrier rates of HLA-B alleles, determined by direct sequencing, were compared between cases and controls. Results were meta-analyzed with previous studies to examine the associations between HLA-B*15:02 and SJS/TEN induced by phenytoin and lamotrigine. KEY FINDINGS: A total of 55 cases (27 carbamazepine, 15 phenytoin, 6 lamotrigine, 7 other AEDs) and 275 controls were recruited. In drug-specific analysis, the carrier rate of HLA-B*15:02 was significantly higher in carbamazepine-SJS/TEN cases compared with carbamazepine-tolerant controls (92.3% vs. 11.9%; p = 3.51 × 10(-18) ; odds ratio (OR) 89.25; 95% confidence interval (CI) 19.25-413.83), and also in phenytoin-SJS/TEN cases compared with phenytoin-tolerant controls (46.7% vs. 20.0%; p = 0.045; OR 3.50; 95% CI 1.10-11.18). Meta-analyses showed a strong association of HLA-B*15:02 with phenytoin-SJS/TEN (p < 3 × 10(-4) ; OR 4.26; 95% CI 1.93-9.39) and, to a lesser extent, lamotrigine-SJS/TEN (p = 0.03; OR 3.59; 95% CI 1.15-11.22). Compared with drug-tolerant controls, the carrier rates of HLA-B*40:01 and HLA-B*58:01 were lower in cases of SJS/TEN induced by carbamazepine (p = 0.004) and other AEDs (p = 0.009), respectively. SIGNIFICANCE: SJS/TEN induced by carbamazepine and phenytoin is strongly and moderately associated with HLA-B*15:02 in Han Chinese, respectively. Possible protective associations with HLA-B*40:01 and HLA-B*58:01 warrant further investigation.

Allergic rhinitis and risk of erectile dysfunction--a nationwide population-based study.

BACKGROUND: A growing body of evidence has disclosed that allergic rhinitis (AR) is a systemic inflammatory disease. Inflammatory mediators and cells involved in AR have also been reported to be implicated in the process of atherosclerosis, which is relevant to the occurrence of erectile dysfunction (ED). Our objective was to explore the relationship between AR and future ED events. METHODS: From 1 January 2000 to 31 December 2008, we identified male patients, who were aged 18-55 years and newly diagnosed with AR from the Taiwan National Health Insurance Research Database. A control cohort without AR, which was matched for age, comorbidities and medications, was selected for comparison. The two cohorts were followed up until 31 December 2009 and observed for occurrence of ED by registry of ED diagnosis in the database. RESULTS: Of the 128,118 sampled male patients (64,059 AR patients vs 64,059 matched controls), 1455 (1.16%) experienced ED during a mean follow-up period of 5.82 years, including 844 (1.32% of the AR patients) from the AR cohort and 611 (0.95%) from the controls. Kaplan-Meier analysis revealed a tendency of AR patients to develop ED (log-rank test, P < 0.001). After adjusting confounder variables by Cox regression, subjects with AR experienced a 1.37-fold (95% CI, 1.24-1.52; P < 0.001) increase in incident ED. The risk of ED was higher in cases with more frequent clinical visits for AR and in cases needing medication more than 4 weeks. CONCLUSIONS: Patients with AR appeared to be at higher risk of future ED, possibly in a severity-dependent manner.

Parenteral vitamin B12 in macrocytic hemodialysis patients reduced MMA levels but did not change mean red cell volume or hemoglobin.

AIMS: Unexplained macrocytic anemia was common in our hemodialysis (HD) unit. Vitamin B12 requirements may be higher in HD patients; therefore, patients may be deficient despite "normal" serum levels. We studied vitamin B12 status and the effect of parenteral vitamin B12 administration in macrocytic HD patients. A normocytic group was included for comparison. MATERIALS AND METHODS: Prospective cohort study of 62 HD patients (34 macrocytic, 28 normocytic) from November 2008 to March 2009. Patients were on stable doses of darbepoetin and iron replete. Vitamin B12 1,000 µg IV was given once weekly for 4 weeks and follow-up was 12 weeks. Methylmalonic acid (MMA) level was used as an indicator of vitamin B12 status. MCV and hemoglobin were also examined for an effect of B12 administration. RESULTS: At baseline: all patients had serum B12 levels > 200 pmol/l; 97% had serum folate levels > 55 nmol/l; there was no difference in serum B12 levels between groups (504 vs. 571 pmol/l, p = 0.18); MMA was higher in the macrocytic group (0.56 vs. 0.48 µmol/l, p = 0.048) and hemoglobin (Hg) was lower (119 vs. 125 g/l, p = 0.03); median darbepoetin dose was equivalent (20 µg/week). Following IV vitamin B12, the macrocytic group had a greater and more sustained reduction in MMA (-0.064 vs. -0.0066 µmol/l/wk, p = 0.004). There was no improvement in hemoglobin (Hg), reticulocyte count or MCV in either group. Median darbepoetin dose was unchanged. CONCLUSIONS: IV vitamin B12 led to a sustained decline in MMA levels in macrocytic patients, suggesting functional vitamin B12 deficiency at baseline. However, there were no significant changes in Hg or darbepoetin dose.

Comparison of primary care experiences among adults in general outpatient clinics and private general practice clinics in Hong Kong.

BACKGROUND: The main goal of Hong Kong's publicly-funded general outpatient clinics (GOPCs) is to provide primary medical services for the financially vulnerable. The objective of the current study was to compare the primary care experiences of GOPC users and the users of care provided by private general practitioners (GPs) in Hong Kong via a territory-wide telephone survey. METHODS: One thousand adults in Hong Kong aged 18 and above were interviewed by a telephone survey. The modified Chinese translated Primary Care Assessment Tool was used to collect data on respondents' primary care experience. RESULTS: Our results indicated that services provided by GOPC were more often used by female, older, poorer, chronically-ill and less educated population. GOPC participants were also more likely to have visited a specialist or used specialist services (69.7% vs. 52.0%; p < 0.001), although this difference in utilization of specialist services disappeared after adjusting for age (55.7% vs. 52.0%, p = 0.198). Analyses were also performed to asses the relationship between healthcare settings (GOPCs versus private GPs) and primary care quality. Private GP patients achieved higher overall PCAT scores largely due to better accessibility (Mean: 6.88 vs. 8.41, p < 0.001) and person-focused care (Mean: 8.37 vs. 11.69, p < 0.001). CONCLUSIONS: Our results showed that patients primarily receiving care from private GPs in Hong Kong reported better primary care experiences than those primarily receiving care from GOPCs. This was largely due to the greater accessibility and better interpersonal relationships offered by the private GPs. As most patients use both GOPCs and private GPs, their overall primary care experiences may not be as different as the findings of this study imply.

A systematic evaluation of payback of publicly funded health and health services research in Hong Kong.

BACKGROUND: The Health and Health Services Research Fund (HHSRF) is dedicated to support research related to all aspects of health and health services in Hong Kong. We evaluated the fund's outcomes and explored factors associated with the translation of research findings to changes in health policy and provider behaviour. METHODS: A locally suitable questionnaire was developed based on the "payback" evaluation framework and was sent to principal investigators of the completed research projects supported by the fund since 1993. Research "payback" in six outcome areas was surveyed, namely knowledge production, use of research in the research system, use of research project findings in health system policy/decision making, application of the research findings through changed behaviour, factors influencing the utilization of research, and health/health service/economic benefits. RESULTS: Principal investigators of 178 of 205 (87%) completed research projects returned the questionnaire. Investigators reported research publications in 86.5% (mean = 5.4 publications per project), career advancement 34.3%, acquisition of higher qualifications 38.2%, use of results in policy making 35.4%, changed behaviour in light of findings 49.4%, evidence of health service benefit 42.1% and generated subsequent research in 44.9% of the projects. Payback outcomes were positively associated with the amount of funding awarded. Multivariate analysis found participation of investigators in policy committees and liaison with potential users were significantly associated with reported health service benefit (odds ratio [OR]participation = 2.86, 95% confidence interval [CI] 1.28-6.40; ORliaison = 2.03, 95% CI 1.05-3.91), policy and decision-making (ORparticipation = 10.53, 95% CI 4.13-26.81; ORliaison = 2.52, 95% CI 1.20-5.28), and change in behavior (ORparticipation = 3.67, 95% CI 1.53-8.81). CONCLUSION: The HHSRF has produced substantial outcomes and compared favourably with similar health research funds in other developed economies. Further studies are needed to better understand the factors and pathways associated with the translation of research findings into practice.

Genetic analysis of Nicotiana pollen-part mutants is consistent with the presence of an S-ribonuclease inhibitor at the S locus.

Self-incompatibility (SI) is a genetic mechanism that restricts inbreeding in flowering plants. In the nightshade family (Solanaceae) SI is controlled by a single multiallelic S locus. Pollen rejection in this system requires the interaction of two S locus products: a stylar (S)-RNase and its pollen counterpart (pollen S). pollen S has not yet been cloned. Our understanding of how this gene functions comes from studies of plants with mutations that affect the pollen but not the stylar SI response (pollen-part mutations). These mutations are frequently associated with duplicated S alleles, but the absence of an obvious additional allele in some plants suggests pollen S can also be deleted. We studied Nicotiana alata plants with an additional S allele and show that duplication causes a pollen-part mutation in several different genetic backgrounds. Inheritance of the duplication was consistent with a competitive interaction model in which any two nonmatching S alleles cause a breakdown of SI when present in the same pollen grain. We also examined plants with presumed deletions of pollen S and found that they instead have duplications that included pollen S but not the S-RNase gene. This finding is consistent with a bipartite structure for the S locus. The absence of pollen S deletions in this study and perhaps other studies suggests that pollen S might be required for pollen viability, possibly because its product acts as an S-RNase inhibitor.

Evidence for nucleomorph to host nucleus gene transfer: light-harvesting complex proteins from cryptomonads and chlorarachniophytes.

Cryptomonads and chlorarachniophytes acquired photosynthesis independently by engulfing and retaining eukaryotic algal cells. The nucleus of the engulfed cells (known as a nucleomorph) is much reduced and encodes only a handful of the numerous essential plastid proteins normally encoded by the nucleus of chloroplast-containing organisms. In cryptomonads and chlorarachniophytes these proteins are thought to be encoded by genes in the secondary host nucleus. Genes for these proteins were potentially transferred from the nucleomorph (symbiont nucleus) to the secondary host nucleus; nucleus to nucleus intracellular gene transfers. We isolated complementary DNA clones (cDNAs) for chlorophyll-binding proteins from a cryptomonad and a chlorarachniophyte. In each organism these genes reside in the secondary host nuclei, but phylogenetic evidence, and analysis of the targeting mechanisms, suggest the genes were initially in the respective nucleomorphs (symbiont nuclei). Implications for origins of secondary endosymbiotic algae are discussed.

A molecular description of mutations affecting the pollen component of the Nicotiana alata S locus.

Mutations affecting the self-incompatibility response of Nicotiana alata were generated by irradiation. Mutants in the M1 generation were selected on the basis of pollen tube growth through an otherwise incompatible pistil. Twelve of the 18 M1 plants obtained from the mutagenesis screen were self-compatible. Eleven self-compatible plants had mutations affecting only the pollen function of the S locus (pollen-part mutants). The remaining self-compatible plant had a mutation affecting only the style function of the S locus (style-part mutant). Cytological examination of the pollen-part mutant plants revealed that 8 had an extra chromosome (2n + 1) and 3 did not. The pollen-part mutation in 7 M1 plants was followed in a series of crosses. DNA blot analysis using probes for S-RNase genes (encoding the style function of the S locus) indicated that the pollen-part mutation was associated with an extra S allele in 4 M1 plants. In 3 of these plants, the extra S allele was located on the additional chromosome. There was no evidence of an extra S allele in the 3 remaining M1 plants. The breakdown of self-incompatibility in plants with an extra S allele is discussed with reference to current models of the molecular basis of self-incompatibility.

Bioassay of biotin concentration with a Escherichia coli bio deletion mutant.

Biotin concentration was determined unequivocally with the E. coli bio mutant. The results demonstrate that this simple and efficient method can determine biotin concentration in the range of 10 pg to 50 ng/ml. The present method can also clearly distinguish biotin from its precursor and analog, dethiobiotin.

Nucleotide sequencing of S-RNA segment and sequence analysis of the nucleocapsid protein gene of the newly isolated Akabane virus PT-17 strain.

The nucleotide sequences of the S-RNA of Akabane viruses JaGAr-39, OBE-1, Iriki and the newly isolated PT-17 strains and the Aino virus were determined and compared. The results reveal that the S-RNAs of the four Akabane strains share 96.9% homology in nucleotide sequences. Only one amino acid difference out of the 233 amino acids of the nucleocapsid protein (N) and three amino acid differences in the 91 amino acids of the nonstructural protein (NSs) were found among the Akabane viruses. Amino acid sequences of N and NSs proteins of the Aino virus have approximately 80% identity as compared with the Akabane viruses. The results also demonstrate that the four Akabane viruses and the Aino virus can be clearly differentiated by RFLP (restriction fragments length polymorphism) analysis using RT-PCR generated nucleocapsid protein genes and digested with HaeIII and HindIII. The phylogenetic tree based on the UPGMA (Unweighted Pair Group Method with Arithmetic Mean) analysis of the sequences of nucleocapsid protein genes and the S-DNAs revealed that the newly isolated PT-17 strain is most closely related to Iriki strain, than the JaGAr-39 or OBE-1 strains.