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The Ti–15Mo alloy has become a widely recognized biomedical Ti alloy due to its excellent properties, including a low Young’s modulus that is close to that of a human bone. Selective laser melting (SLM) additive manufacturing (AM) offers both advanced manufacturing capabilities to the processing of the alloy and the potential to make customized implants. The feedstock cost of pre-alloyed Ti–15Mo powder, however, is high, like that of many other Ti alloys, and can be a major obstacle to the wider application of the AM technique. This study focused on mitigating this problem by using an in situ laser alloying approach, wherein a low-cost hydride-dehydrate (HDH) Ti powder was mechanically mixed with elemental Mo powder to form a composite powder feedstock (i.e., Ti + Mo). The Ti–15Mo alloy could be printed with a high relative density (~ 99.76%). A finite element simulation was performed to study the melt pool during the SLM process with subsequent detailed discussions to understand the in situ alloying mechanism. Mechanical property indicates the as-printed Ti–15Mo has high strength (~ 1170 MPa) but low ductility, while the latter has been much improved by introducing a merely 0.2 wt% of yttrium (Y). Based on the optimized Ti–15Mo–0.2Y alloy with a strength of ~ 1300 MPa and a modulus of ~ 85 GPa, different amounts of elemental Ag powder were further alloyed in situ to acquire antibacterial properties. Compared with the antibacterial activity of the control group, that of the final material, i.e., in situ laser alloyed Ti–15Mo–0.2Y–2.5Ag, reached 92–95%; the addition of Ag had a minimal effect on the cell viability. In vivo experiments demonstrated the Ag-containing alloys to exhibit good biocompatibility. Graphical Abstract

To investigate the prevalence of, and risk factors for, cervical infection with human papillomavirus (HPV) in Shenyang City, People's Republic of China, we interviewed and obtained cervical cell samples from 685 women aged 15–59 years enumerated from local population lists. Human papillomavirus DNA was detected in cervical cell samples using a GP5+/6+-based PCR assay for 44 HPV types. Human papillomavirus prevalence was 16.8% overall and 13.6% among women without cervical abnormalities (16.6% and 12.4%, respectively, age-standardised to the world standard population), with no significant trends in HPV prevalence by age group. Of the 32 types identified, high-risk HPV types predominated in all age groups, HPV16 being the most common (3.4% of all women), followed by HPV52 (2.5%) and 58 (1.9%). Multiple-type infections accounted for 31.3% of all infected women. Not being married, reporting multiple sexual partners and husband's extramarital sexual relationships were all significantly associated with being HPV-positive. The disclosure of a relatively high HPV prevalence in Shenyang, in comparison with other worldwide populations, raises important questions concerning the prevention of cervical cancer in China, especially given the promising efficacy of prophylactic HPV vaccines.

Studies indicate that environmental exposure to lead is associated with reduced renal function. Whether lead affects progressive diabetic nephropathy is unclear. Eighty-seven patients with type II diabetes and diabetic nephropathy (serum creatinine of 1.5–3.9 mg/dl) with normal body lead burden and no lead exposure history were observed over a 12-month period. Thirty subjects with high normal body lead burdens (80–600 μg) were randomly assigned to a chelation and control group. For 3 months, the 15 chelation-group patients underwent lead-chelation therapy with calcium disodium ethylenediaminetetraacetic acid weekly until body lead burden fell <60 μg, and the 15 control group subjects received a weekly placebo. During the following 12 months, renal function was regularly assessed at 3-month intervals. The primary outcome was an elevation of serum creatinine to 1.5 times baseline value during the observation period. A secondary outcome was temporal changes in renal function following chelation therapy. Twenty-six patients achieved the primary outcome. Basal blood lead levels and body lead burden were the most important risk factors in predicting progressive diabetic nephropathy. Following chelation, the rates of decline in glomerular filtration rates in the chelation group and the control group, respectively, were 5.0±5.7 ml and 11.8±7.0 ml/min/year/1.73 m2 of body surface area (P=0.0084) during follow-up, although both groups had similar rates of progression of renal function during the 12-month observation period. We concluded that low-level environmental lead exposure accelerates progressive diabetic nephropathy and lead-chelation therapy can decrease its rate of progression.

To evaluate alternative cervical cancer screening methods, digital colposcopy and collection of cervical exfoliated cells for liquid-based cytology (LBC) and hybrid capture 2 (HC2) testing were performed among 2562 women aged 15–59 years in three study sites in the People's Republic of China (rural Shanxi province, Shenyang city in Liaoning province and Shenzhen city in Guangdong province). Visual inspection with acetic acid (VIA) was also evaluated independently from colposcopy. A total of 74 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified, and 16 CIN2+ cases were imputed among unbiopsied women to correct for verification bias. Corrected sensitivity for CIN2+ was 37% for VIA, 54% for colposcopy, 87% for LBC with a threshold of atypical cells of undetermined significance (LBC⩾ASCUS), 90% for HC2, 84% for LBC using HC2 to triage ASCUS and 96% for positivity to LBC⩾ASCUS or HC2. For VIA, sensitivity was much lower among women ⩾40 years (12%) than those aged ⩽39 years (50%). Specificity varied from 77% for positivity to LBC⩾ASCUS or HC2, up to 94% for LBC using HC2 to triage ASCUS. In conclusion, LBC, HC2 and their combinations performed well, whereas VIA missed a majority of CIN2+, particularly in older women. Digital colposcopy performed better than VIA, but still missed nearly half of CIN2+ in this study.

Introduction/Background*Pembrolizumab has efficacy in previously treated, PD-L1-positive advanced cervical cancer. KEYNOTE-826 (NCT03635567) was a phase 3, randomised, double-blind trial of pembrolizumab or placebo added to chemotherapy ± bevacizumab for first-line treatment of recurrent, persistent, or metastatic cervical cancer.MethodologyEligible adults had persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy and not amenable to curative treatment. Patients were randomised 1:1 to pembrolizumab 200 mg or placebo Q3W for ≤35 cycles added to chemotherapy (paclitaxel plus cisplatin or carboplatin) ± bevacizumab and stratified by metastatic status at diagnosis, planned bevacizumab use, and PD-L1 combined positive score (CPS). Dual primary endpoints were PFS (RECIST v1.1, investigator review) and OS tested sequentially in the CPS ≥1, all-comer, and CPS ≥10 populations.Result(s)*617 patients were randomized: 308 to pembrolizumab plus chemotherapy (63.6% with bevacizumab) and 309 to placebo plus chemotherapy (62.5% with bevacizumab); 548 (88.8%) patients had CPS ≥1, 317 (51.4%) had CPS ≥10. At the protocol-specified first interim analysis, pembrolizumab plus chemotherapy ± bevacizumab significantly improved PFS in the CPS ≥1 (median, 10.4 vs 8.2 months; HR, 0.62 [95% CI, 0.50–0.77]; P<0.001), all-comer (10.4 vs 8.2 months; 0.65 [0.53–0.79]; P<0.001), and CPS ≥10 (10.4 vs 8.1 months; 0.58 [0.44–0.77]; P<0.001) populations. OS was also significantly improved in the CPS ≥1 (median, not reached [NR] vs 16.3 months; HR, 0.64 [95% CI, 0.50–0.81]; P<0.001), all-comer (24.4 vs 16.5 months; 0.67 [0.54–0.84]; P<0.001), and CPS ≥10 (NR vs 16.4 months; 0.61 [0.44–0.84]; P=0.001) populations. Benefits were seen in the with and without bevacizumab subgroups. The incidence of grade ≥3 AEs was 81.8% in the pembrolizumab arm and 75.1% in the placebo arm. Anaemia and neutropenia were the most common grade ≥3 AEs (30.3% vs 26.9% and 12.4% vs 9.7%, respectively).Conclusion*Pembrolizumab plus chemotherapy ± bevacizumab significantly improves OS and PFS in patients with persistent, recurrent, or metastatic cervical cancer. Along with a manageable safety profile, the clinically meaningful survival benefits suggest pembrolizumab plus chemotherapy ± bevacizumab may be a new standard first-line therapy for this population.

Background The purpose of this study was to prospectively evaluate the efficacy and safety of remote magnetic navigation (RMN) in comparison with manual catheter navigation (MCN) in performing ventricular tachycardia ablation. Methods An electronic search was performed using PubMed (1948–2013) and EMBASE (1974–2013) studies comparing RMN with MCN which were published prior to 31 December 2013. Outcomes of interest were as follows: acute success, recurrence rate, complications, total procedure and fluoroscopic times. Standard mean difference (SMD) and its 95 % confidence interval (CI) were used for continuous outcomes; odds ratios (OR) were reported for dichotomous variables. Results Four non-randomised studies, including a total of 328 patients, were identified. RMN was deployed in 191 patients. Acute success and long-term freedom from arrhythmias were not significantly different between the RMN and control groups (OR 1.845, 95 % CI 0.731–4.659, p  = 0.195 and OR 0.676, 95 % CI 0.383–1.194, p  = 0.177, respectively). RMN was associated with less peri-procedural complications (OR 0.279, 95 % CI 0.092–0.843, p  = 0.024). Shorter procedural and fluoroscopy times were achieved (95 % CI -0.487 to -0.035, p  = 0.024 and 95 % CI -1.467 to -0.984, p <0.001, respectively). Conclusion The acute and long-term success rates for VT ablation are equal between RMN and MCN, whereas the RMN-guided procedure can be performed with a lower complication rate and less procedural and fluoroscopic times. More prospective randomised trials will be needed to better evaluate the superior role of RMN for catheter ablation of ventricular tachycardia.

The Ti-15Mo alloy has become a widely recognized biomedical Ti alloy due to its excellent properties, including a low Young's modulus that is close to that of a human bone. Selective laser melting (SLM) additive manufacturing (AM) offers both advanced manufacturing capabilities to the processing of the alloy and the potential to make customized implants. The feedstock cost of pre-alloyed Ti-15Mo powder, however, is high, like that of many other Ti alloys, and can be a major obstacle to the wider application of the AM technique. This study focused on mitigating this problem by using an in situ laser alloying approach, wherein a low-cost hydride-dehydrate (HDH) Ti powder was mechanically mixed with elemental Mo powder to form a composite powder feedstock (i.e., Ti + Mo). The Ti-15Mo alloy could be printed with a high relative density ( 99.76%). A finite element simulation was performed to study the melt pool during the SLM process with subsequent detailed discussions to understand the in situ alloying mechanism. Mechanical property indicates the as-printed Ti-15Mo has high strength ( 1170 MPa) but low ductility, while the latter has been much improved by introducing a merely 0.2 wt% of yttrium (Y). Based on the optimized Ti-15Mo-0.2Y alloy with a strength of 1300 MPa and a modulus of 85 GPa, different amounts of elemental Ag powder were further alloyed in situ to acquire antibacterial properties. Compared with the antibacterial activity of the control group, that of the final material, i.e., in situ laser alloyed Ti-15Mo-0.2Y-2.5Ag, reached 92-95%; the addition of Ag had a minimal effect on the cell viability. In vivo experiments demonstrated the Ag-containing alloys to exhibit good biocompatibility.

Children with developmental disabilities usually move from the paediatric to adult health service after the age of 18 years. This clinical transition is fragmented in Hong Kong. There are no local data for adolescents with developmental disabilities and their families about the issues they face during the clinical transition. This pilot study aimed to explore and collect information from adolescents with developmental disabilities and their caregivers about their transition from paediatric to adult health care services in Hong Kong. This exploratory survey was carried out in two special schools in Hong Kong. Convenient samples of adolescents with developmental disabilities and their parents were taken. The questionnaire was administered by interviewers in Cantonese. Descriptive statistics were used to analyse the answers to closed-ended questions. Responses to open-ended questions were summarised. In this study, 22 parents (mean age ± standard deviation: 49.9 ± 10.0 years) and 13 adolescents (19.6 ± 1.0 years) completed the face-to-face questionnaire. The main diagnoses of the adolescents were cerebral palsy (59%) and cognitive impairment (55%). Of the study parents, 77% were reluctant to transition. For the 10 families who did move to adult care, 60% of the parents were not satisfied with the services. The main reasons were reluctant to change and dissatisfaction with the adult medical service. The participants emphasised their need for a structured clinical transition service to support them during this challenging time. This study is the first in Hong Kong to present preliminary data on adolescents with developmental disabilities and their families during transition from paediatric to adult medical care. Further studies are required to understand the needs of this population group during clinical transition.

Abstract Transient noise (“glitches”) in gravitational wave detectors can mimic or obscure true signals, significantly reducing detection sensitivity. Identifying and excluding glitch-contaminated data segments is therefore crucial for enhancing the performance of gravitational-wave searches. We perform a noise analysis of the KAGRA data obtained during the O3GK observation. Our analysis is performed with hierarchical veto (Hveto) which identifies noises based on the statistical time correlation between the main channel and the auxiliary channels. A total of 2531 noises were vetoed by 28 auxiliary channels with the configuration (i.e. signal-to-noise threshold set to 8) that we chose for Hveto. We identify vetoed events as glitches on the spectrogram via visual examination after plotting them with Q-transformation. By referring to the Gravity Spy project, we categorize 2354 glitches into 6 types: blip, helix, scratchy, and scattered light, which correspond to those listed in Gravity Spy, and dot and line, which are not found in the Gravity Spy classification and are thus named based on their spectrogram morphology in the KAGRA data. The remaining 177 glitches are determined not to belong to any of these six types. We show how the KAGRA glitch types are related to each subsystem of KAGRA. To investigate the possible correlation between the main channel and the round winner—an auxiliary channel statistically associated with the main channel for vetoing purposes—we visually examine the similarity or difference in the glitch pattern on the spectrogram. We compare the qualitative correlation found through visual examination with coherence, which is known to provide quantitative measurement for the correlation between the main channel and each auxiliary channel. Our comprehensive noise analysis will help improve the data quality of KAGRA by being applied to future KAGRA observation data.

Estimating crop nutrient requirements for winter oilseed rape (Brassica napus L.) is a crucial step in optimizing fertilization to enhance seed yield and improve fertilizer use efficiency. In the present paper, a database composed of 1035 on-farm observations collected from 2005 to 2010 across the major winter oilseed rape production regions in China was used to evaluate internal nutrient efficiencies (kg seed per kg nutrient in plant dry matter); then the Quantitative Evaluation of the Fertility of Tropical Soils (QUEFTS) model for winter oilseed rape was developed to describe the nutrient uptake-yield relationship of oilseed rape over a wide range of environmental conditions and predict the nutrient requirements for a target yield. After excluding observations with low harvest index values, <0·20, and excluding 0·025 of the highest and lowest internal nutrient efficiencies, the minimum and maximum internal nutrient efficiencies were estimated as 13·1 and 31·6 kg seed/kg nitrogen (N), 68·9 and 200·3 kg seed/kg phosphorus (P) and 8·9 and 31·1 kg seed/kg potassium (K), respectively. On the basis of the data settings, the balanced N, P and K uptake at different yield potential levels was calculated using a linear–parabolic–plateau curve with the QUEFTS model. Crop nutrient requirements increased linearly until the yield reached approximately 0·60–0·70 of the potential yield, and 46·0 kg N, 8·0 kg P and 57·1 kg K were found to be needed to produce 1000 kg of seed. The corresponding internal nutrient efficiencies were 21·8, 125·1 and 17·5 kg seed/kg N, P and K, respectively. However, when the target yields approached the yield potential, a decrease in internal nutrient efficiencies was detected in the model. The predicted nutrient requirement values simulated by the QUEFTS model compared well with observed values across a range of conditions. To conclude, the QUEFTS model was shown to be a practical and robust tool for assessing the crop nutrient requirements of winter oilseed rape.