Amine-terminated nanoparticle films: pattern deposition by a simple nanostencilling technique and stability studies under X-ray irradiation

Exploring the surface chemistry of nanopatterned amine-terminated nanoparticle films.</p

Graphene-wrapped sulfur/metal organic framework-derived microporous carbon composite for lithium sulfur batteries

A three-dimensional hierarchical sandwich-type graphene sheet-sulfur/carbon (GS-S/CZIF8-D) composite for use in a cathode for a lithium sulfur (Li-S) battery has been prepared by an ultrasonic method. The microporous carbon host was prepared by a one-step pyrolysis of Zeolitic Imidazolate Framework-8 (ZIF-8), a typical zinc-containing metal organic framework (MOF), which offers a tunable porous structure into which electro-active sulfur can be diffused. The thin graphene sheet, wrapped around the sulfur/zeolitic imidazolate framework-8 derived carbon (S/CZIF8-D) composite, has excellent electrical conductivity and mechanical flexibility, thus facilitating rapid electron transport and accommodating the changes in volume of the sulfur electrode. Compared with the S/CZIF8-D sample, Li-S batteries with the GS-S/CZIF8-D composite cathode showed enhanced capacity, improved electrochemical stability, and relatively high columbic efficiency by taking advantage of the synergistic effects of the microporous carbon from ZIF-8 and a highly interconnected graphene network. Our results demonstrate that a porous MOF-derived scaffold with a wrapped graphene conductive network structure is a potentially efficient design for a battery electrode that can meet the challenge arising from low conductivity and volume change.National Science Foundation of China (21373028)This is the final version of the article. It first appeared from American Institute of Physics Publishing via http://dx.doi.org/10.1063/1.490175

A snow and glacier hydrological model for large catchments – case study for the Naryn River, central Asia

In this paper we implement a degree day snowmelt and glacier melt model in the Dynamic fluxEs and ConnectIvity for Predictions of HydRology (DECIPHeR) model. The purpose is to develop a hydrological model that can be applied to large glaciated and snow-fed catchments yet is computationally efficient enough to include model uncertainty in streamflow predictions. The model is evaluated by simulating monthly discharge at six gauging stations in the Naryn River catchment (57 833 km2) in central Asia over the period 1951 to a variable end date between 1980 and 1995 depending on the availability of discharge observations. The spatial distribution of simulated snow cover is validated against MODIS weekly snow extent for the years 2001–2007. Discharge is calibrated by selecting parameter sets using Latin hypercube sampling and assessing the model performance using six evaluation metrics. The model shows good performance in simulating monthly discharge for the calibration period (NSE is 0.74&lt;NSE&lt;0.87) and validation period (0.7&lt;NSE&lt;0.9), where the range of NSE values represents the 5th–95th percentile prediction limits across the gauging stations. The exception is the Uch-Kurgan station, which exhibits a reduction in model performance during the validation period attributed to commissioning of the Toktogul reservoir in 1975 which impacted the observations. The model reproduces the spatial extent in seasonal snow cover well when evaluated against MODIS snow extent; 86 % of the snow extent is captured (mean 2001–2007) for the median ensemble member of the best 0.5 % calibration simulations. We establish the present-day contributions of glacier melt, snowmelt and rainfall to the total annual runoff and the timing of when these components dominate river flow. The model predicts well the observed increase in discharge during the spring (April–May) associated with the onset of snow melting and peak discharge during the summer (June, July and August) associated with glacier melting. Snow melting is the largest component of the annual runoff (89 %), followed by the rainfall (9 %) and the glacier melt component (2 %), where the values refer to the 50th percentile estimates at the catchment outlet gauging station Uch-Kurgan. In August, glacier melting can contribute up to 66 % of the total runoff at the highly glacierized Naryn headwater sub-catchment. The glaciated area predicted by the best 0.5 % calibration simulations overlaps the Landsat observations for the late 1990s and mid-2000s. Despite good predictions for discharge, the model produces a large range of estimates for the glaciated area (680–1196 km2) (5th–95th percentile limits) at the end of the simulation period. To constrain these estimates further, additional observations such as glacier mass balance, snow depth or snow extent should be used directly to constrain model simulations.</p

Near-Infrared Classification Spectroscopy: H-band Spectra of Fundamental MK Standards

We present a catalogue of H-band spectra for 85 stars of approximately solar abundance observed at a resolving power of 3000 with the KPNO Mayall 4m FTS. The atlas covers spectral types O7-M5 and luminosity classes I-V as defined on the MK system. We identify both atomic and molecular indices and line-ratios which are temperature and luminosity sensitive allowing spectral classification to be carried out in the H-band. The line ratios permit spectral classification in the presence of continuum excess emission, which is commonly found in pre-main sequence and evolved stars. We demonstrate that with spectra of R = 1000 obtained at SNR > 50 it is possible to derive spectral types within +- 2 subclasses for late-type stars. These data are available electronically through the Astronomical Data Center in addition to being served on the World-Wide-Web.Comment: To appear in the November 20, 1998 issue of ApJ (Volume 508, #1

Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial

Background: Peri-operative chemotherapy and surgery is a standard of care for patients with resectable oesophagogastric adenocarcinoma. Bevacizumab, a monoclonal antibody against VEGF, improves the proportion of patients responding to treatment in advanced gastric cancer. We aimed to assess the safety and efficacy of adding bevacizumab to peri-operative chemotherapy in patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Methods: In this multicentre, randomised, open-label phase 2–3 trial, we recruited patients aged 18 years and older with histologically proven, resectable oesophagogastric adenocarcinoma from 87 UK hospitals and cancer centres. We randomly assigned patients 1:1 to receive peri-operative epirubicin, cisplatin, and capecitabine chemotherapy or chemotherapy plus bevacizumab, in addition to surgery. Patients in the control group (chemotherapy alone) received three pre-operative and three post-operative cycles of epirubicin, cisplatin, and capecitabine chemotherapy: 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 and 1250 mg/m2 oral capecitabine on days 1–21. Patients in the investigational group received the same treatment as the control group plus 7·5 mg/kg intravenous bevacizumab on day 1 of every cycle of chemotherapy and for six further doses once every 21 days following chemotherapy, as maintenance treatment. Randomisation was done by means of a telephone call to the Medical Research Council Clinical Trials Unit, where staff used a computer programme that implemented a minimisation algorithm with a random element to establish the allocation for the patient at the point of randomisation. Patients were stratified by chemotherapy centre, site of tumour, and tumour stage. The primary outcome for the phase 3 stage of the trial was overall survival (defined as the time from randomisation until death from any cause), analysed in the intention-to-treat population. Here, we report the primary analysis results of the trial; all patients have completed treatment and the required number of primary outcome events has been reached. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 46020948, and with ClinicalTrials.gov, number NCT00450203. Findings: Between Oct 31, 2007, and March 25, 2014, 1063 patients were enrolled and randomly assigned to receive chemotherapy alone (n=533) or chemotherapy plus bevacizumab (n=530). At the time of analysis, 508 deaths were recorded (248 in the chemotherapy alone group and 260 in the chemotherapy plus bevacizumab group). 3-year overall survival was 50·3% (95% CI 45·5–54·9) in the chemotherapy alone group and 48·1% (43·2–52·7) in the chemotherapy plus bevacizumab group (hazard ratio [HR] 1·08, 95% CI 0·91–1·29; p=0·36). Apart from neutropenia no other toxic effects were reported at grade 3 or worse severity in more than 10% of patients in either group. Wound healing complications were more prevalent in the bevacizumab group, occurring in 53 (12%) patients in this group compared with 33 (7%) patients in the chemotherapy alone group. In patients who underwent oesophagogastrectomy, post-operative anastomotic leak rates were higher in the chemotherapy plus bevacizumab group (23 [10%] of 233 in the chemotherapy alone group vs 52 [24%] of 220 in the chemotherapy plus bevacizumab group); therefore, recruitment of patients with lower oesophageal or junctional tumours planned for an oesophagogastric resection was stopped towards the end of the trial. Serious adverse events for all patients included anastomotic leaks (30 events in chemotherapy alone group vs 69 in the chemotherapy plus bevacizumab group), and infections with normal neutrophil count (42 events vs 53). Interpretation: The results of this trial do not provide any evidence for the use of bevacizumab in combination with peri-operative epiribicin, cisplatin, and capecitabine chemotherapy for patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Bevacizumab might also be associated with impaired wound healing. Funding: Cancer Research UK, MRC Clinical Trials Unit at University College London, and F Hoffmann-La Roche Limited

Activity interventions to improve the experience of care in hospital for people living with dementia: A systematic review

This is the final version. Available from the publisher via the DOI in this record.Background: An increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. Methods: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. Results: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. Conclusions: The small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.National Institute for Health Research (NIHR

The experiences of hospital staff who provide care for people living with dementia: A systematic review and synthesis of qualitative studies

This is the final version. Available from the publisher via the DOI in this record.Aims and objectives: To systematically review and synthesise qualitative data from studies exploring the experiences of hospital staff who care for people living with dementia (Plwd). Background: In hospital, the number of Plwd continues to rise; however, their experiences of care remain problematic. Negative experiences of care are likely to contribute to poorer mental and physical health outcomes for Plwd while in hospital and after discharge. Experiences of the hospital staff who care for Plwd can also be poor or unrewarding. It is important to understand the experiences of staff in order to improve staff well-being and ultimately the experience of care for Plwd while in hospital. Design: Systematic review and evidence synthesis of qualitative research. Data sources: We searched 16 electronic databases in March 2018 and completed forward and backward citation chasing. Methods: Eligible studies explored the experiences of paid and unpaid staff providing care in hospital for Plwd. Study selection was undertaken independently by two reviewers, and quality appraisal was conducted. We prioritised included studies according to richness of text, methodological rigour and conceptual contribution. We adopted approaches of meta-ethnography to analyse study findings, creating a conceptual model to represent the line of argument. Findings: Forty-five studies reported in 58 papers met the inclusion criteria, and of these, we prioritised 19 studies reported in 24 papers. The line of argument was that Institutions can improve staff experiences of care for Plwd by fostering person-centred care (PCC). PCC aligned with staff perceptions of ‘good care’; however, staff often felt prevented from providing PCC because of care cultures that prioritised tasks, routines and physical health. Staff experienced conflict over the care they wanted to give versus the care they were able to give, and this caused moral distress. When staff were able to provide PCC, this increased experiences of job satisfaction and emotional well-being. Conclusions: Person-centred care not only has the potential to improve the experience of care for Plwd and their carers, but can also improve the experiences of hospital staff caring for Plwd. However, without institutional-level changes, hospital staff are often unable to provide PCC even when they have the experience and knowledge to do so. Implications for practice: Institutional-level areas for change include the following: training; performance indicators and ward cultures that prioritise psychological needs alongside physical needs; adequate staffing levels; inclusive approaches to carers; physical environments that promote familiarisation, social interaction and occupation; systems of documentation about individual needs of Plwd; and cultures of sharing knowledge across hierarchies.National Institute for Health Research (NIHR

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors

A universal synthetic route to carbon nanotube/transition metal oxide nano-composites for lithium ion batteries and electrochemical capacitors.

We report a simple synthetic approach to coaxially grow transition metal oxide (TMO) nanostructures on carbon nanotubes (CNT) with ready control of phase and morphology. A thin (~4 nm) sulfonated-polystyrene (SPS) pre-coating is essential for the deposition of transition metal based materials. This layer has abundant sulfonic groups (-SO3(-)) that can effectively attract Ni(2+), Co(2+), Zn(2+) ions through electrostatic interaction and induce them via hydrolysis, dehydration and recrystallization to form coaxial (NiO, Co3O4, NiCoO2 and ZnCo2O4) shells and a nanosheet-like morphology around CNT. These structures possess a large active surface and enhanced structural robustness when used as electrode materials for lithium-ion batteries (LIBs) and electrochemical capacitors (ECs). As electrodes for LIBs, the ZnCo2O4@CNT material shows extremely stable cycling performance with a discharge capacity of 1068 mAh g(-1) after 100 cycles at a current density of 400 mAg(-1). For EC applications, the NiCoO2@CNT exhibits a high capacitance of 1360 Fg(-1) at current densities of 10 Ag(-1) after 3000 cycles and an overall capacitance loss of only 1.4%. These results demonstrate the potential of such hybrid materials meeting the crucial requirements of cycling stability and high rate capability for energy conversion and storage devices

Structure-guided design of purine-based probes for selective Nek2 inhibition

Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can restrict tumor cell growth and promote apoptosis. Nek2 inhibition with small molecules, therefore, offers the prospect of a new therapy for cancer. To achieve this goal, a better understanding of the requirements for selective-inhibition of Nek2 is required. 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Comparison with CDK2-inhibitor structures indicated that judicious modification of the 6-alkoxy and 2-arylamino substituents could achieve discrimination between Nek2 and CDK2. In this study, a library of 6-cyclohexylmethoxy-2-arylaminopurines bearing carboxamide, sulfonamide and urea substituents on the 2-arylamino ring was synthesized. Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 μM; Nek2 IC50 = 0.62 μM) with >10-fold selectivity. Deletion of the 6-substituent abrogated activity against both Nek2 and CDK2. Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 μM; Nek2 IC50 = 0.27 μM). Structural biology of selected compounds enabled a partial rationalization of the observed structure activity relationships and mechanism of Nek2 activation. This showed that carboxamide 11 is the first reported inhibitor of Nek2 in the DFG-in conformation