High-peak-power optically pumped passively mode-locked semiconductor laser with minimal components.

A high-peak-power sub-500-fs mode-locked optically pumped semiconductor laser is innovatively developed with only three components of a semiconductor gain chip, a semiconductor saturable absorber, and a focusing lens. The developed laser near the threshold pump power of 3.9 W can be operated with stable fundamental mode locking. The laser output can be naturally turned into the stable harmonic mode locking (HML) with the order gradually changing from 2nd to 8th by increasing the pump power from 4.0 W to 5.0 W. Due to the onset of the high-order transverse modes, the order of HML is fixed at 8th for a pump power greater than 5.0 W. For the HML with order less than 8th, the overall peak power and pulse width in the HML are approximately 0.36 kW and 550 fs, respectively. In the operation of 8th-order HML, the minimum pulse width and maximum peak power can reach 480 fs and 0.95 kW, respectively.

The Effectiveness of Frailty Intervention for Older Patients with Frailty during Hospitalization.

OBJECTIVES: This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults. DESIGN: This single-arm, prospective, non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling. SETTING AND PARTICIPANTS: At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3-7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward. INTERVENTION: Those receiving standard care (physical rehabilitation and nutrition counseling) during January-July 2019 composed the historical control group. Those receiving the multidomain intervention during August-December 2019 composed the intervention group. MEASUREMENTS: The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes. RESULTS: Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11-1.11; p = 0.02; CFS adjusted estimate, -1.11; 95% CI, -1.42- -0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, -7.99- -2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49-0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR [aOR], 0.12; 95% CI, 0.27-0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01-0.33; p < 0.01) than did controls. CONCLUSIONS: Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.

Urban-rural disparity of preventive healthcare utilisation among children under the universal health insurance coverage in Taiwan: a national birth cohort analysis.

OBJECTIVE: In the context of universal health insurance coverage, this study aimed to determine whether urban-rural inequality still exists in preventive health care (PHC) amongst children in Taiwan. STUDY DESIGN: Prospective cohort study. METHODS: A total of 184,117 mothers and their children born in 2009 were identified as the study cohort. The number of children born in urban, satellite and rural areas was 40,176, 57,565 and 86,805, respectively. All children were followed for 7 years, before which a total of seven times PHC were provided by Taiwan's National Health Insurance (NHI) programme. Ordinal logistic regression models were used to associate urbanisation level with the frequency of PHC utilisation. Stratified analyses were further performed in accordance with the children's birth weight and the mothers' birthplace. RESULTS: Children from satellite areas had higher utilisation for the first four scheduled PHC visits. Children living in urban areas received more PHC for the fifth and sixth scheduled visits. Compared with those from rural areas, children in satellite areas exhibited a small but significant increase in odds in PHC utilisation, with a covariate-adjusted odds ratio (aOR) of 1.04 and 95% confidence interval (CI) of 1.02-1.06. By contrast, no significant difference was observed between rural and urban areas (aOR = 1.01). Further stratified analyses suggest more evident urban-rural difference in PHC utilisation amongst children with low birth weight and foreign-born mothers. CONCLUSIONS: Given a universal health insurance coverage and embedded mechanisms in increasing the availability of healthcare resources in Taiwan, a slight urban-rural difference is observed in PHC utilisation amongst children. Hence, sociodemographic inequality in utilisation of PHC still exists. This issue should be addressed through policy intervention.

The Adverse Effects of Physical Restraint Use among Older Adult Patients Admitted to the Internal Medicine Wards: A Hospital-Based Retrospective Cohort Study.

OBJECTIVES: To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients. DESIGN: A retrospective cohort study. SETTING: Internal medicine wards of a tertiary medical center in Taiwan. PARTICIPANTS: Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study. MEASUREMENTS: Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis. RESULTS: Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322-3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627-7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794-7.160, p<0.001) after adjustment for covariates. CONCLUSION: The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.

Predictive Effect of Malnutrition on Long-Term Clinical Outcomes among Older Men: A Prospectively Observational Cohort Study.

OBJECTIVES: To determine whether nutritional status can predict 3-year cognitive and functional decline, as well as 4-year all-cause mortality in older adults. DESIGN: Prospectively longitudinal cohort study. SETTING AND PARTICIPANTS: The study recruited 354 men aged 65 years and older in the veteran's retirement community. MEASURES: Baseline nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Cognitive function and Activities of Daily Living (ADL) function were determined by the Mini-Mental State Examination (MMSE) and the Barthel Index, respectively. Three-year cognitive and functional decline were respectively defined as a >3 point decrease in the MMSE scores and lower ADL scores than at baseline. Univariate and multivariable logistic regression analyses were conducted to identify nutritional status as a risk factor in poor outcome. The Kaplan-Meier method and Cox proportional regression models were used to estimate the effect of malnutrition risk on the mortality. RESULTS: According to MNS-SF, the prevalence of risk of malnutrition was 53.1% (188/354). Multivariate logistic regression found risk of malnutrition significantly associated with 3-year cognitive decline (Adjusted odds ratio [OR] 2.07, 95% Confidence Interval [CI] 1.05-4.08, P =0.036) and functional decline (Adjusted OR 1.83, 95% CI 1.01-3.34, P =0.047) compared with normal nutritional status. The hazard ratio (HR) for all-cause mortality was 1.8 times higher in residents at risk of malnutrition (Adjusted HR 1.82, 95% CI 1.19-2.79, P =0.006). CONCLUSIONS: Our results provide strong evidence that risk of malnutrition can predict not only cognitive and functional decline but also risk of all-cause mortality in older men living in a veteran retirement's community. Further longitudinal studies are needed to explore the causal relationship among nutrition, clinical outcomes, and the effect of an intervention for malnutrition.

Heritability and social brood effects on personality in juvenile and adult life-history stages in a wild passerine.

How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype or because our concept of personality and the stability of behaviour needs to be revised.

Age-dependent trajectories differ between within-pair and extra-pair paternity success.

Reproductive success is associated with age in many taxa, increasing in early life followed by reproductive senescence. In socially monogamous but genetically polygamous species, this generates the interesting possibility of differential trajectories of within-pair and extra-pair siring success with age in males. We investigate these relationships simultaneously using within-individual analyses with 13 years of data from an insular house sparrow (Passer domesticus) population. As expected, we found that both within- and extra-pair paternity success increased with age, followed by a senescence-like decline. However, the age trajectories of within- and extra-pair paternity successes differed significantly, with the extra-pair paternity success increasing faster, although not significantly, in early life, and showing a delayed decline by 1.5 years on average later in life compared to within-pair paternity success. These different trajectories indicate that the two alternative mating tactics should have age-dependent pay-offs. Males may partition their reproductive effort between within- and extra-pair matings depending on their current age to reap the maximal combined benefit from both strategies. The interplay between these mating strategies and age-specific mortality may explain the variation in rates of extra-pair paternity observed within and between species.

Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials.

AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74-1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. CONCLUSIONS: Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted.

Use of non-steroidal anti-inflammatory drugs and risk of chronic kidney disease in people with Type 2 diabetes mellitus, a nationwide longitudinal cohort study.

AIMS: To investigate the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus. METHODS: We conducted a retrospective cohort study and followed up a population with Type 2 diabetes who were chronic kidney disease-free (n = 48,715) using national health insurance claims data in Taiwan. Exposure status to non-steroidal anti-inflammatory drugs in 2007 was measured. A total of 6406 subjects with incident chronic kidney disease were identified from the period 2008 to 2011. Multivariable proportional hazards models were applied to determine the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease. RESULTS: We observed a significant temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes. Compared with people not taking any non-steroidal anti-inflammatory drug in 2007, those who were taking such drugs for at least 90 days in 2007 had a higher risk of chronic kidney disease development (adjusted hazard ratio 1.37, 95% CI 1.26-1.49). In subgroup analyses, those people (irrespective of age, sex, various comorbidities and use of anti-hypertensive drugs, aspirin or acetaminophen) who were taking non-steroidal anti-inflammatory drugs for at least 90 days were more likely to develop chronic kidney disease than people who were not taking any non-steroidal anti-inflammatory drug. CONCLUSIONS: The results suggest that there is a positive temporal relationship between non-steroidal anti-inflammatory drug use and increased risk of chronic kidney disease in people with Type 2 diabetes. The use of non-steroidal anti-inflammatory drugs should be based on clinical evaluations of benefits and risks, and should be prescribed with caution for people with Type 2 diabetes.

Highly cited articles in health care sciences and services field in Science Citation Index Expanded. A bibliometric analysis for 1958 - 2012.

OBJECTIVE: This study aimed to identify and analyze characteristics of highly cited articles published in the Web of Science category of health care sciences and services from 1958 to 2012. METHODS: Articles that have been cited at least 100 times were assessed regarding publication outputs, distribution of outputs in journals, publications of authors, institutions, countries as well as citation life cycles of the articles with the highest total citations since its publication up to 2012 and the highest citations in 2012. Six bibliometric indicators were used to evaluate source countries, institutions, and authors. Total citations from the time the articles were first published to the end of 2012 and citations in 2012 only were applied. Additionally, Y-index was applied to evaluate publication characteristics of authors. A high percentage of authors had the same numbers of first author and corresponding author status of highly cited articles in health care sciences and services field. RESULTS: RESULTS showed that 890 of the most highly referenced articles, published between 1977 and 2009, had been cited at least 100 times. Medical Care and Journal of General Internal Medicine published the most highly cited articles. The United States produced 76% of highly cited articles and also published the most number of independent, internationally collaborative, first authored, corresponding authored, and single author highly cited articles. The Harvard University was the most productive institute and was number one for the total highly cited articles, inter-institutionally collaborative articles, single institution articles, first author articles, and corresponding author articles. CONCLUSIONS: The application of quantitative techniques in the analysis of highly cited articles can improve the researchers' understanding of the directions in health care sciences and services field. Y-index is useful for the evaluation of contributing authors.

Note: Three-dimensional linearization of optical trap position detection for precise high speed diffusion measurements.

Studies of the details of Brownian motion, hydrodynamic of colloids, or protein diffusion measurements all require high temporal and spatial resolution of the position detector and a means to trap the colloid. Optical trap based thermal noise imaging employing a quadrant photodiode as detector provides such a method. However, optical trapping requires an objective with high numerical aperture resulting in highly nonlinear position signal and significant cross-dependence of the three spatial directions. Local diffusion measurements are especially susceptible to distance errors. Here, we present a position calibration method, which corrects nonlinearities sufficiently to allow precise local diffusion measurement throughout the entire trapping volume. This correction permits us to obtain high-resolution two- and three-dimensional diffusion maps.

Co-occurrence of second primary malignancy in patients with thyroid cancer.

BACKGROUND: The discovery of asynchronous or synchronous double or multiple malignancies in patients is not uncommon. The co-occurrence of second primary malignancy (SPM) could be randomly occurring or association with risk factors such as environmental, genetic predisposition and therapy-related. MATERIALS AND METHODS: We retrieved ∼782 million claim records consisting of 10.8 million males and 10.6 million females from Taiwan's National Health Insurance, which were collected for a period of 3 years (January 2000-December 2002). All the patient records were stratified by gender and ages at a 20-year interval with SPMs and specific groups. Interestingness or Q-value was used to measure strength of the disease-disease associations. RESULTS: A total of 9423 thyroid cancer (female: 7483, male: 1940), 276 184 SPM (female: 141 023, male: 135 161) and 861 co-occurrence cases (female: 583, male: 278) were recorded. The co-occurrence incidence rate of head and neck, breast, digestive system and lung was 1.93%, 1.59%, 1.44% and 1.18%, respectively. Malignancy of salivary glands, laryngx, sarcoma, lymphoid tissue, mouth, central nervous system and lungs found Q-value >10. Malignancies with intermediate Q-values (5.0-9.9) were observed in nasopharynx, kidney and ureter, breast, stomach and skin. Prostate, leukemia, urinary bladder, ovary, colon, liver and uterine cervix cancer have lower Q-values (1.0-4.9). CONCLUSION: Co-occurrence ratio of thyroid cancer and SPM was high, occurred in all organ systems. We postulated that the aggressive use of modern diagnostic modalities, aggressive radioiodine treatment, pre-existing molecular oncogen mutations, and thyroid hormone for simultaneously supple-mentary and suppressive therapies were responsible.

Cardiologist service volume, percutaneous coronary intervention and hospital level in relation to medical costs and mortality in patients with acute myocardial infarction: a nationwide study.

BACKGROUND: We explore whether cardiologist service volume, hospital level and percutaneous coronary intervention (PCI) are associated with medical costs and acute myocardial infarction (AMI) mortality. METHODS: From the 1997-2010 Taiwan National Health Insurance Research Database of the National Health Research Institute, we identified AMI patients and performed multiple regression analyses to explore the relationships among the different hospital levels and treatment factors. RESULTS: We identified 2942 patients with AMI in medical centers and 4325 patients with AMI in regional hospitals. Cardiologist service volume, performing PCI and medical costs per patient were higher in medical centers than in regional hospitals (P < 0.0001). However, the two hospital levels did not differ significantly in in-hospital mortality (P = 0.1557). Post hoc analysis showed significant differences in in-hospital mortality rate and in medical costs among the eight groups subdivided on the basis of hospital level, cardiologist service volume, and whether PCI was performed (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: These results highlight the importance of encouraging hospitals to develop PCI capability and increase their cardiologist service volume after taking medical costs into account. Transferring AMI patients to hospitals with higher cardiologist service volume and PCI performed can also be very important.

Association between serum ferritin and microalbuminuria in Type 2 diabetes in Taiwan.

AIMS: Serum ferritin has been found closely related with diabetes and glucose metabolism, but its impact on diabetic nephropathy remains unknown. This study aimed to explore the association between serum ferritin and microalbuminuria in Type 2 diabetes. METHODS: Eight hundred and fifty-one subjects with Type 2 diabetes were selected from a cohort participating in a glycaemic control study in Taiwan in 2008. We used urine albumin:creatinine ratio to define microalbuminuria; serum ferritin was divided into quartiles for analysis. Logistic regression and trend tests were used to delineate the association between serum ferritin and microalbuminuria. RESULTS: Subjects with diabetes with higher ferritin tended to have more metabolic disorders, higher high-sensitivity C-reactive protein and higher prevalence of microalbuminuria. Compared with those in the lowest quartile, subjects with diabetes in the highest ferritin quartile were 55% (P = 0.029) more likely to have microalbuminuria. After controlling for demographics, metabolic profiles and other inflammatory markers, the association between serum ferritin levels and microalbuminuria remained significant (P for trend < 0.001). This independent relationship was not changed either for those who had better glycaemic control or those who had not used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSIONS: The current study shows hyperferritinemia may be an independent risk factor of nephropathy in patients with Type 2 diabetes.

Investigation of Mannheimia haemolytica bacteriophages relative to host diversity.

AIMS: This study aimed to characterize the impact of lytic and temperate bacteriophages on the genetic and phenotypic diversity of Mannheimia haemolytica from feedlot cattle. METHODS AND RESULTS: Strictly lytic phages were not detected from bovine nasopharyngeal (n = 689) or water trough (n = 30) samples, but Myoviridae- or Siphoviridae-like phages were induced from 54 of 72 M. haemolytica strains by mitomycin C, occasionally from the same strain. Phages with similar restriction fragment length polymorphism profiles (RFLP ≥70% relatedness) shared common host serotypes 1 or 2 (P < 0·0001). Likewise, phages with similar RFLP tended to occur in genetically related host bacteria (70-79% similarity). Host range assays showed that seven phages from host serotypes 1, 2 and 6 lysed representative strains of serotypes 1, 2 or 8. The genome of vB_MhM_1152AP from serotype 6 was found to be collinear with P2-like phage φMhaA1-PHL101. CONCLUSIONS: Prophages are a significant component of the genome of M. haemolytica and contribute significantly to host diversity. Further characterization of the role of prophage in virulence and persistence of M. haemolytica in cattle could provide insight into approaches to control this potential respiratory pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that prophages are widespread within the genome of M. haemolytica isolates and emphasized the challenge of isolating lytic phage as a therapeutic against this pathogen.

Effects of protein coding polymorphisms in the kallikrein 1 gene on baseline blood pressure and antihypertensive response to irbesartan in Chinese hypertensive patients.

The aim of this study was to determine the association between coding variants in the human tissue kallikrein 1 (KLK1) gene and baseline blood pressure (BP) and antihypertensive response to irbesartan treatment in Chinese hypertensive patients. A total of 1061 hypertensives were recruited and received daily oral dosage of 150 mg irbesartan for 4 weeks. Predose BPs, BPs and blood irbesartan concentrations at postdose on the 28th day were all measured. Common functional single-nucleotide polymorphisms (SNPs) in the KLK1 gene were genotyped. On the basis of the HapMap data of Han Chinese in the Beijing population, two non-synonymous polymorphisms with minor allele frequency>0.1, SNP rs5517 (Glu162Lys) and rs5516 (Gln121Glu), were selected. Those with GG genotype in the rs5516 locus had higher average baseline systolic BP (SBP) than CC subjects (ß±s.e.: 5.0±2.3, P=0.033); and no associations of rs5517 with baseline BP (diastolic BP (DBP) and SBP) and BP responses, or rs5516 with baseline DBP and BP response were observed. In a haplotype-based association test for the KLK1 gene, the Haplo-special score analyses identified that haplotype AG was marginally associated with SBP response (specific score: 1.75 for P=0.08), but not with DBP response. We did not find any associations between haplotypes (GC and AC) and BP responses. The Haplo-GLM analyses showed that, compared with haplotype GC subjects, the subjects with haplotype AG had a marginally greater SBP response (adjusted ß±s.e.: 1.81±0.97, P=0.06), but DBP response did not differ. This study suggests that rs5516 in the KLK1 gene may be involved in the development of essential hypertension and in the regulation of SBP-lowering response to irbesartan in Chinese hypertensives.

MR spectroscopy and MR perfusion character of cerebral sparganosis: a case report.

The authors report the case of a 46-year-old woman with cerebral sparganosis resulting from infection with a larva of Spirometra. Computed tomography and magnetic resonance imaging revealed a mass lesion with prominent perifocal oedema in the left parietal lobe. Advanced imaging pulse sequences, including MR spectroscopy and MR perfusion, were performed. During surgery for the removal of a granuloma, the parasite was discovered and excised. Following treatment, the patient's neurological deficits markedly improved.

Mechanical properties of three different compositions of calcium phosphate bioceramic following immersion in Ringer's solution and distilled water.

Dissolution tests were carried out to compare the mechanical properties of calcium phosphate based bioceramics with different compositions, before and after ageing for various time periods in Ringer's solution (pH 7.2) or distilled water (pH 7.2 and 4.0) at 37 degrees C. The results indicate that the sample composition seems to have more of an effect on the mechanical properties than does the storage environment. No obvious decrease in mechanical properties was found after samples had been aged in the various solutions during the different time periods. This indicates that these samples could be of significant clinical interest as their good structural properties were retained.