bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening and characterization of a novel high‐efficiency tumor‐homing cell‐penetrating peptide from the buffalo cathelicidin family
Authors: Xu Yuan‐Yuan , Cao Xue‐Wei , Fu Long‐Yun , Zhang Tao‐Zhu , Wang Fu‐Jun , Zhao Jian
Published: July 2019

Targeted delivery of antitumor drugs is especially important for tumor therapy. Cell‐penetrating peptides (CPPs) have been shown to be very effective drug carriers for tumor therapy. However, most CPPs lack tumor cell specificity. Here, we identified a highly efficient CPP, CAT, from the newly identified buffalo‐derived cathelicidin family, which exhibits a preferential binding capacity for multiple tumor cell lines and delivers carried drug molecules into cells. CAT showed an approximately threefold to sixfold higher translocation efficiency than some reported cell‐penetrating antimicrobial peptides, including the well‐known classical CPP TAT. Moreover, the delivery efficiency of CAT was greater in a variety of tested tumor cells than in normal cells, especially for the human hepatoma cell line SMMC‐7721, for which delivery was 7 times more efficient than the normal human embryonic lung cell line MRC‐5, according to fluorescent labeling experiment results. CAT was conjugated to the Momordica charantia‐derived type‐I ribosome‐inactivating protein MAP 30, and the cytotoxicity of the MAP 30‐CAT fusion protein in the tumor cell line SMMC‐7721 was significantly enhanced compared with that of the unconjugated MAP 30. The IC50 value of MAP 30‐CAT was approximately 83 times lower than the IC50 value of the original MAP 30. Interestingly, the IC50 value of MAP 30 alone for MRC‐5 was approximately twofold higher than the value for SMMC‐7721, showing a small difference. However, when MAP 30 was conjugated to CAT, the difference in IC50 values between the two cell lines was significantly increased by 38‐fold. The results of the flow cytometric detection of apoptosis revealed that the increase in cytotoxicity after CAT conjugation was mainly caused by the increased induction of apoptosis by the fusion protein. These results suggest that CAT, as a novel tumor‐homing CPP, has great potential in drug delivery applications in vivo and will be beneficial to the development of tumor therapeutics.
Reference‐based sensitivity analysis for time‐to‐event data
Authors: Atkinson Andrew , Kenward Michael G. , Clayton Tim , Carpenter James R.
Published: July 2019

The analysis of time‐to‐event data typically makes the censoring at random assumption, ie, that—conditional on covariates in the model—the distribution of event times is the same, whether they are observed or unobserved (ie, right censored). When patients who remain in follow‐up stay on their assigned treatment, then analysis under this assumption broadly addresses the de jure, or “while on treatment strategy” estimand. In such cases, we may well wish to explore the robustness of our inference to more pragmatic, de facto or “treatment policy strategy,” assumptions about the behaviour of patients post‐censoring.

This is particularly the case when censoring occurs because patients change, or revert, to the usual (ie, reference) standard of care. Recent work has shown how such questions can be addressed for trials with continuous outcome data and longitudinal follow‐up, using reference‐based multiple imputation. For example, patients in the active arm may have their missing data imputed assuming they reverted to the control (ie, reference) intervention on withdrawal. Reference‐based imputation has two advantages: (a) it avoids the user specifying numerous parameters describing the distribution of patients' postwithdrawal data and (b) it is, to a good approximation, information anchored, so that the proportion of information lost due to missing data under the primary analysis is held constant across the sensitivity analyses. In this article, we build on recent work in the survival context, proposing a class of reference‐based assumptions appropriate for time‐to‐event data. We report a simulation study exploring the extent to which the multiple imputation estimator (using Rubin's variance formula) is information anchored in this setting and then illustrate the approach by reanalysing data from a randomized trial, which compared medical therapy with angioplasty for patients presenting with angina.
The effect of green tea on inflammatory mediators: A systematic review and meta‐analysis of randomized clinical trials
Authors: Haghighatdoost Fahimeh , Hariri Mitra
Published: July 2019

Catechin in green tea might be able to reduce inflammatory mediators; therefore, in this study, we aimed to indicate green tea effects on inflammatory mediators such as tumor necrosis factor‐alpha (TNF‐α), C‐reactive protein (CRP), and interleukin‐6 (IL‐6). The advanced search methods of electronic databases were used to find randomized clinical trials that assessed green tea effect on inflammatory mediators among adult population. Google Scholar, PubMed/Medline, EMBASE, SCOPUS, and ISI Web of Science were searched until January 2019. Delphi checklist was used for assessing the quality of included articles. Mean changes in serum inflammatory biomarkers were calculated by subtracting endpoint values from the baseline in each study arm. Then the effect size for each selected study was estimated as the difference between mean changes in the intervention and control groups. We included 16 articles in our meta‐analysis and 17 articles in systematic review. Our results indicated that green tea could not significantly decrease serum CRP levels and significantly increased IL‐6 and significantly decreased TNF‐α levels. In conclusion, green tea might not be able to change inflammatory mediators especially in diseases with low inflammation, but scientists who want to assess green tea effect on inflammatory mediators should perform their study on patients with high inflammation. Studies exclusive on male or female and considering nutrients intake as a confounding factor are a necessity.
Change in fish community composition following weir removal, field observations, and physical habitat simulations
Authors: Im Dongkyun , Choi Byungwoong , Choi Sung‐Uk
Published: July 2019

The number of untended weirs has increased in Korea in recent years due to land use changes. The removal of abandoned weirs in streams has been attempted following an agreement between local government and residents. The Gongneung Weir‐2 was built for irrigation in the 1970s and was removed in 2006. The objective of this study was to investigate the impact of the removal of Gongneung Weir‐2 on the composition of the fish community. The study area was a 900‐m‐long reach in the Gongneung‐cheon River in Korea, and Gongneung Weir‐2 was located in the middle of the reach. Before weir removal, field monitoring revealed that five fish species were dominant and accounted for more than 80% of the entire fish community. The composition of the fish community changed significantly after weir removal. Lotic fish became dominant after weir removal, whereas lentic fish were dominant prior to weir removal. Physical habitat simulations (PHSs) for individual dominant fish species were carried out. For the PHS, the River2D model and the adaptive neuro‐fuzzy inference system method were used for hydraulic and habitat simulations, respectively. The distributions of the highly suitable portion for each fish species were identified before and after weir removal. The PHS successfully predicted changes in the composition of the fish community after weir removal. The PHSs for the entire fish community and for the lotic and lentic guilds were undertaken and the simulated results were compared with each other. The PHSs for the entire fish community could not account for the less dominant fish species in the fish community.
Spatio‐temporal variability of suspended sediments in rivers and ecological implications of reservoir flushing operations
Authors: Tritthart Michael , Haimann Marlene , Habersack Helmut , Hauer Christoph
Published: July 2019

High suspended sediment concentrations during reservoir flushing are known to be harmful to biota in downstream river stretches. Therefore, it is common practice to set legal concentration limits for upstream reservoir management operations such as flushings or controlled drawdowns. However, as shown by measurements, there is a considerable spatio‐temporal variability of suspended sediment concentrations both in the longitudinal profile of rivers and in river cross‐sections. To consider this variability in management operations, SED‐FISH—a three‐dimensional modelling approach—was developed to study this variability in a wider context by upscaling cross‐sectional measurements of suspended sediments to high‐resolution three‐dimensional information on the reach scale in an alpine river. The resulting patterns of suspended sediment concentrations were integrated over their respective time of occurrence for various scenarios in order to calculate severity of harmful impacts for target fish species. The modelling results identified refugial habitats with reduced negative impacts in near‐bank zones even for relatively high suspended sediment concentrations in the centre of the river. Moreover, a substantially larger variability of both suspended sediment concentrations and associated harmful impacts was found for a winding riverbed morphology as compared with a straight reach. Both these findings and the developed modelling tool could assist in establishing individual case‐based concentration limits for reservoir management operations in the future and should also be taken into account when planning river regulation or restoration measures.
Goosebumps‐Inspired Microgel Patterns with Switchable Adhesion and Friction
Authors: Li Bin , Kappl Michael , Han Lu , Cui Jiaxi , Zhou Feng , del Campo Aránzazu
Published: July 2019

A substrate mimicking the surface topography and temperature sensitivity of skin goosebumps is fabricated. Close‐packed arrays of thermoresponsive microgel particles undergo topographical changes in response to temperature changes between 25 and 37 °C, resembling the goosebump structure that human skin develops in response to temperature changes or other circumstances. Specifically, positively charged poly[2‐(methacryloyloxy)ethyltrimethylammonium chloride] (PMETAC) brushes serve as an anchoring substrate for negatively charged poly(NIPAm‐co‐AA) microgels. The packing density and particle morphology can be tuned by brush layer thickness and pH of the microgel suspension. For brush layer thickness below 50 nm, particle monolayers are observed, with slightly flattened particle morphology at pH 3 and highly collapsed particles at pH above 7. Polymer brush films with thickness above 50 nm lead to the formation of particle multilayers. The temperature responsiveness of the monolayer assemblies allows reversible changes in the film morphology, which in turn affects underwater adhesion and friction at 25 and 37 °C. These results are promising for the design of new functional materials and may also serve as a model for biological structures and processes.
Development of air conditioner operation planning method using people flow information
Authors: Nakamura Ryosuke , Kawamura Tsutomu
Published: July 2019

We developed a method for controlling air conditioning, in which the output of the air conditioners is determined on the basis of the thermal load predicted from people flow data. When the upper limit of power consumption is given, the air conditioners are operated so as not to exceed that limit. This is done by strengthening the air conditioning output before the peak limit is violated. Three advantages are obtained with this method. First, the contract demand is reduced, so the basic charges are reduced. Second, the air conditioner capacity is reduced, so the replacement cost is reduced. Last, the comfort level is maintained even when the air conditioner capacity is smaller than the thermal load. These effects were evaluated with data obtained from an example case and verified. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Invariant Measures for the Stochastic One-Dimensional Compressible Navier–Stokes Equations
Authors: Coti Zelati Michele , Glatt-Holtz Nathan , Trivisa Konstantina
Published: July 2019

We investigate the long-time behavior of solutions to a stochastically forced one-dimensional Navier–Stokes system, describing the motion of a compressible viscous fluid, in the case of linear pressure law. We prove existence of an invariant measure for the Markov process generated by strong solutions. We overcome the difficulties of working with non-Feller Markov semigroups on non-complete metric spaces by generalizing the classical Krylov–Bogoliubov method, and by providing suitable polynomial and exponential moment bounds on the solution, together with pathwise estimates.
Influence of Daily Variations in Individual Surgeon's Operative Time on Patient Outcomes
Authors: Meunier Etienne , Payet Cécile , Peix Jean‐Louis , Kraimps Jean‐Louis , Menegaux Fabrice , Pattou François , Sebag Fréderic , Lifante Jean Christophe , Duclos Antoine ,   the CATHY study group
Published: July 2019

Background

Evidence is lacking regarding the potential association between daily variation in individual surgeon's operative time, procedure after procedure, and risk of patient complication. We assumed that surgeon deviation from the expected procedure duration may be harmful for patient.

Method

All patients who underwent a thyroidectomy undertaken in five hospitals during a 1‐year period were included prospectively. For each thyroidectomy, we estimated the expected operative time from a multilevel linear regression considering the attending surgeon who performed the operation, the patient preoperative risk, and the procedure complexity. Three groups of thyroidectomies were identified according to whether the observed duration is: slower than expected, as expected, or faster than expected. Rates of permanent recurrent laryngeal nerve palsy and hypoparathyroidism at 6 months were then compared between these groups.

Results

A total of 3102 patients who underwent a thyroidectomy undertaken by 22 surgeons were considered. Risk of laryngeal nerve palsy was higher in the “slow” group than in the “normal” group (OR = 4.63, 95% confidence interval 2.21–9.70), as was that of hypoparathyroidism (OR = 2.43, 95% confidence interval 1.21–4.88). There was no significant difference between “fast” and “normal” groups for either complication. Deviation from expected procedure duration was more frequent at the end than at the beginning of the daily operation schedule (29.4% vs. 18.3%, respectively, P < .001).

Conclusion

Patients had a greater risk of complication when the surgeon performed thyroidectomy slower than expected. Surgeons avoiding excessive deviations from their expected procedures durations reflect safer practice.
Herausforderung der Varianteninterpretation am Beispiel des Long-QT-Syndroms (LQTS)
Authors: Marschall Christoph , Moscu-Gregor Alexander , Rost Imma
Published: July 2019

Die „Next-generation Sequencing (NGS)“-Technologie ermöglicht es, alle bekannten LQTS-Gene in der Diagnostik parallel zu analysieren. Dies führt dazu, dass in zunehmendem Maße Varianten nachgewiesen werden, deren klinische Bedeutung unklar ist. Erschwerend macht sich hierbei bemerkbar, dass abgesehen von den drei gut beschriebenen Hauptgenen KCNQ1, KCNH2 und SCN5A, deren Varianten für ca. 70 % der Erkrankungsfälle verantwortlich sind, die Evidenz für eine ursächliche Beteiligung einiger „Nebengene“ nur mäßig oder umstritten ist. Um eine Flut unklarer Befunde zu vermeiden und die Notwendigkeit ausgedehnter familiärer Segregationsstudien zu begrenzen sowie Fehlinterpretationen vorzubeugen, sind eine fundierte Auswahl der zu analysierenden Gene sowie ein transparentes und allgemein anerkanntes System der Variantenklassifikation essenziell. Die ACMG-Richtlinien sind der derzeitige Konsens zur Klassifikation von Varianten. Allerdings zeigen sich bei der Anwendung Limitationen, sodass diese Richtlinien nur eine Basis darstellen, die durch differenziertere Systeme verbessert werden kann.

Bei den Bestrebungen nach einer personalisierten Medizin werden große Hoffnungen auf Genotyp-Phänotyp-Zusammenhänge gesetzt. In LQTS-Proteinen wurden einige funktionell relevante Regionen wie die Poren der Kalium- und Natriumkanäle, in denen Varianten tendenziell schwerwiegende Phänotypen hervorrufen, beschrieben. Darüber hinaus zeigen dominant-negative Varianten in der Regel stärkere Effekte als „loss-of-function“ (LoF)-Varianten. Dennoch ist eine differenzielle Therapie nur eingeschränkt möglich. Während Patienten mit Kaliumkanaldefekten mit β‑Blockern behandelt werden, profitieren Patienten mit „gain-of-function“ (GoF)-Varianten in SCN5A von Natriumkanalblockern.
Effectiveness of non-medical health worker-led counselling on psychological distress: a randomized controlled trial in rural Nepal
Authors: Markkula N. , Lehti V. , Adhikari P. , Peña S. , Heliste J. , Mikkonen E. , Rautanen M. , Salama E. , Guragain B.
Published: July 2019

Background.

An essential strategy to increase coverage of psychosocial treatments globally is task shifting to non-medical counsellors, but evidence on its effectiveness is still scarce. This study evaluates the effectiveness of lay psychosocial counselling among persons with psychological distress in a primary health care setting in rural Nepal.

Methods.

A parallel randomized controlled trial in Dang, rural Nepal (NCT03544450). Persons aged 16 and older attending primary care and with a General Health Questionnaire (GHQ-12) score of 6 or more were randomized (1:1) to receive either non-medical psychosocial counselling (PSY) or enhanced usual care (EUC). PSY was provided by lay persons with a 6-month training and consisted of 5-weekly counselling sessions of 35–60 min with a culturally adapted solution-focused approach. EUC was provided by trained primary health workers. Participants were followed up at 1 (T1) and 6 months (T2). The primary outcome, response to treatment, was the reduction of minimum 50% in the Beck Depression Inventory (BDI) score.

Results.

A total of 141 participants, predominantly socially disadvantaged women, were randomized to receive PSY and 146 to EUC. In the PSY, 123 participants and 134 in the EUC were analysed. In PSY, 101 participants (81.4%) had a response compared with 57 participants (42.5%) in EUC [percentage difference 39.4% (95% CI 28.4–50.4)]. The difference in BDI scores at T2 between PSY and EUC was −7.43 (95% CI −9.71 to −5.14).

Conclusions.

Non-medical (lay) psychosocial counselling appears effective in reducing depressive symptoms, and its inclusion in mental health care should be considered in low-resource settings.
A Higher-Order Plate Element Formulation for Dynamic Analysis of Hyperelastic Silicone Plate
Authors: Xu Qiping , Liu Jinyang , Qu Lizheng
Published: July 2019

Most of previous work for modeling and analyzing various traditional linear elastic materials concentrated on numerical simulations based on lower-order absolute nodal coordinate formulation (ANCF) plate element, in which linear interpolation in transverse direction is utilized and stiffening effect caused by volumetric locking occurs. Relatively little attention is paid to modeling hyperelastic incompressible materials with nonlinear effect and large deformation. In view of this, a higher-order plate element formulation with quadratic interpolation in transverse direction for static and dynamic analysis of incompressible hyperelastic silicone material plate is developed in this investigation. The use of higher-order plate element can not only alleviate volumetric locking, but also improve accuracy in simulating large bending deformation as compared to improved lower-order plate element with selective reduced integration method and originally proposed lower-order plate element. Subsequently, experimental investigation that captures free-falling motion of silicone cantilever plate and corresponding simulations are implemented, the results obtained using higher-order plate element are in excellent accordance with experimental data, whereas the results gained applying other two types of plate elements are distinguished from experimental data. Finally, it is concluded that the developed higher-order plate element formulation achieves approving precision and has superiority in simulating large deformation motion of hyperelastic silicone plate.
A NEW MINIMAL NON-σ-SCATTERED LINEAR ORDER
Authors: RAMANDI HOSSEIN LAMEI
Published: July 2019

We will show it is consistent with GCH that there is a minimal non-σ-scattered linear order which does not contain any real or Aronszajn type. In particular the assumption PFA+ in the main result of [5] is necessary, and there are other obstructions than real and Aronszajn types to the sharpness of Laver’s theorem in [8].
Long-term vitamin D and high-dose n-3 fatty acids’ supplementation improve markers of cardiometabolic risk in type 2 diabetic patients with CHD
Authors: Talari Hamid Reza , Najafi Vahid , Raygan Fariba , Mirhosseini Naghmeh , Ostadmohammadi Vahidreza , Amirani Elaheh , Taghizadeh Mohsen , Hajijafari Mohammad , Shafabakhash Rana , Asemi Zatollah
Published: July 2019

This study was performed to evaluate the effects of vitamin D and n-3 fatty acids’ co-supplementation on markers of cardiometabolic risk in diabetic patients with CHD. This randomised, double-blinded, placebo-controlled trial was conducted among sixty-one vitamin D-deficient diabetic patients with CHD. At baseline, the range of serum 25-hydroxyvitamin D levels in study participants was 6·3–19·9 ng/ml. Subjects were randomly assigned into two groups either taking 50 000 IU vitamin D supplements every 2 weeks plus 2× 1000 mg/d n-3 fatty acids from flaxseed oil (n 30) or placebo (n 31) for 6 months. Vitamin D and n-3 fatty acids’ co-supplementation significantly reduced mean (P = 0·01) and maximum levels of left carotid intima–media thickness (CIMT) (P = 0·004), and mean (P = 0·02) and maximum levels of right CIMT (P = 0·003) compared with the placebo. In addition, co-supplementation led to a significant reduction in fasting plasma glucose (β −0·40 mmol/l; 95 % CI −0·77, −0·03; P = 0·03), insulin (β −1·66 μIU/ml; 95 % CI −2·43, −0·89; P < 0·001), insulin resistance (β −0·49; 95 % CI −0·72, −0·25; P < 0·001) and LDL-cholesterol (β −0·21 mmol/l; 95 % CI −0·41, −0·01; P = 0·04), and a significant increase in insulin sensitivity (β +0·008; 95 % CI 0·004, 0·01; P = 0·001) and HDL-cholesterol (β +0·09 mmol/l; 95 % CI 0·01, 0·17; P = 0·02) compared with the placebo. Additionally, high-sensitivity C-reactive protein (β −1·56 mg/l; 95 % CI −2·65, −0·48; P = 0·005) was reduced in the supplemented group compared with the placebo group. Overall, vitamin D and n-3 fatty acids’ co-supplementation had beneficial effects on markers of cardiometabolic risk.
Associations between sweet taste function, oral complex carbohydrate sensitivity, liking and consumption of ad libitum sweet and non-sweet carbohydrate milkshakes among female adults
Authors: Low Julia Y. Q. , Lacy Kathleen E. , McBride Robert L. , Keast Russell S. J.
Published: July 2019

Excess energy intake is recognised as a strong contributing factor to the global rise of being overweight and obese. The aim of this paper was to investigate if oral sensitivity to complex carbohydrate relates to ad libitum consumption of complex carbohydrate foods in a sample group of female adults. Participants’ ((n 51 females): age 23·0 (sd 0·6) years (range 20·0–41·0 years); excluding restrained eaters) sensitivity towards maltodextrin (oral complex carbohydrate) and glucose (sweet taste) was assessed by measuring detection threshold (DT) and suprathreshold intensity perception (ST). A crossover design was used to assess consumption of two different iso-energetic preload milkshakes and ad libitum milkshakes – (1) glucose-based milkshake, (2) maltodextrin-based milkshake. Ad libitum intake (primary outcome) and eating rate, liking, hunger, fullness and prospective consumption ratings were measured. Participants who were more sensitive towards complex carbohydrate (maltodextrin DT) consumed significantly more maltodextrin-based milkshake in comparison with less-sensitive participants (P = 0·01) and this was independent of liking. Participants who had higher liking for glucose-based milkshake consumed significantly more glucose-based milkshake in comparison with participants with lower hedonic ratings (P = 0·049). The results provide support regarding the role of the oral system sensitivity (potentially taste) to complex carbohydrate and the prospective to overconsume complex carbohydrate-based milkshake in a single sitting.
A Race to the Top? The Aid Transparency Index and the Social Power of Global Performance Indicators
Authors: Honig Dan , Weaver Catherine
Published: July 2019

Recent studies on global performance indicators (GPIs) reveal the distinct power that nonstate actors can accrue and exercise in world politics. How and when does this happen? Using a mixed-methods approach, we examine the impact of the Aid Transparency Index (ATI), an annual rating and rankings index produced by the small UK-based NGO Publish What You Fund. The ATI seeks to shape development aid donors' behavior with respect to their transparency—the quality and kind of information they publicly disclose. To investigate the ATI's effect, we construct an original panel data set of donor transparency performance before and after ATI inclusion (2006–2013) to test whether (and which) donors alter their behavior in response to inclusion in the ATI. To further probe the causal mechanisms that explain variations in donor behavior we use qualitative research, including over 150 key informant interviews conducted between 2010 and 2017. Our analysis uncovers the conditions under which the ATI influences powerful aid donors. Our mixed-methods evidence reveals how this happens. Consistent with Kelley and Simmons's central argument that GPIs exercise influence via social pressure, we find that the ATI shapes donor behavior primarily via direct effects on elites: the diffusion of professional norms, organizational learning, and peer pressure.
The blowfish effect: children and adults use atypical exemplars to infer more narrow categories during word learning
Authors: EMBERSON Lauren L. , LONCAR Nicole , MAZZEI Carolyn , TREVES Isaac , GOLDBERG Adele E.
Published: July 2019

Learners preferentially interpret novel nouns at the basic level (‘dog’) rather than at a more narrow level (‘Labrador’). This ‘basic-level bias’ is mitigated by statistics: children and adults are more likely to interpret a novel noun at a more narrow label if they witness ‘a suspicious coincidence’ – the word applied to three exemplars of the same narrow category. Independent work has found that exemplar typicality influences learners’ inferences and category learning. We bring these lines of work together to investigate whether the content (typicality) of a single exemplar affects the level of interpretation of words and whether an atypicality effect interacts with input statistics. Results demonstrate that both four- to five-year-olds and adults tend to assign a narrower interpretation to a word if it is exemplified by an atypical category member. This atypicality effect is roughly as strong as, and independent of, the suspicious coincidence effect, which is replicated.
OPTIMAL R&D SUBSIDIES WITH HETEROGENEOUS FIRMS IN A DYNAMIC SETTING
Authors: Hall Joshua D. , Laincz Christopher A.
Published: July 2019

When observably heterogeneous firms engage in R&D and policy can be conditioned on the heterogeneity, what is the optimal policy? This paper starts with a static duopoly model of R&D competition with uncertainty and finds it welfare enhancing to subsidize the larger firms with no subsidies for the smaller firm, extending existing results. This result follows because the policymaker’s goal is to minimize the average cost of production. Our paper demonstrates that these results are not robust to a dynamic setting. The optimal policy depends on the equilibrium type of competition that emerges without intervention—an insight that cannot be found in a static setting. In a dynamic setting, the degree of competition becomes an endogenous variable. Interestingly, although the optimal policy in some cases provides a slightly larger subsidy for the larger firm, it is the smaller firm that benefits most in terms of firm value.
The effectiveness of hypertension management in China: a community-based intervention study
Authors: Zheng Xiaoguo , Xiao Feng , Li Ruili , Yin Delu , Xin Qianqian , Yang Huimin , Yin Tao , Wang Lihong , Chen Bowen
Published: July 2019

Aim:

This study aimed to evaluate the effectiveness of hypertension management and analyse the factors associated with blood pressure reduction within China’s primary healthcare system.

Background:

Hypertension is one of the leading risk factors for global disease burden and is strongly associated with cardiovascular diseases. In China, hypertension is a serious public health problem, but few studies have evaluated the effectiveness of hypertension management in China’s primary healthcare system.

Methods:

The study sites were 24 primary healthcare institutions, selected using multistage stratified random sampling method. In each institution, hypertension patients aged at least 35 years who agreed to participate and had no disabilities or mental health problems were enrolled for hypertension management. Participants received comprehensive interventions in the primary healthcare system via a team. After a one-year intervention, data from 6575 hypertension patients were analysed to check the effectiveness of hypertension management and examined factors associated with hypertension control.

Findings:

There was an overall mean reduction of 4.5 mmHg in systolic blood pressure (SBP) and 1.9 mmHg in diastolic blood pressure (DBP). The blood pressure reduction after one year was greater in rural patients than in urban patients, 6.6 mmHg versus 3.4 mmHg for SBP and 2.6 mmHg versus 1.6 mmHg for DBP, respectively. The hypertension control rate also increased more in rural areas (22.1%) than in urban areas (10.6%) after the one-year intervention. Age, body mass index, region and being in an urban area had a significant negative association with the reduction of SBP (P< 0.05). Education level and baseline SBP showed a significant positive association (P< 0.05).

Conclusions:

Community-based hypertension management by general practitioners was feasible and effective. The effectiveness of hypertension management in rural areas was greater than in urban areas. Intervention strategies should pay more attention to patients in rural areas and western China.
Role of laboratory services in primary health center (PHC) outpatient department performance: an Indian case study
Authors: Jain Rahi , Rao Bakul
Published: July 2019

Background:

In resource-constrained settings, primary health centers (PHCs) are critical for universal health coverage. Laboratory service is one of its important components. While PHC and its performance are focused, its laboratory service has been neglected in developing countries like India.

Aim:

To determine the role of different level of PHC laboratory services on the overall PHC performance.

Methods:

Cross-sectional study based on 42 PHCs of Osmanabad District, Maharashtra, India was performed. The study used levels of laboratory services in PHC as independent parameter and PHC outpatient department (OPD) visits per day (≤ 80 versus > 80) as dependent parameter. The control parameters used in the study were number of medical doctors, availability of laboratory technicians (LTs) and population coverage by PHC. Field visit was done to collect data on levels of laboratory services, but secondary source was used for other parameters. The logistic regression analysis was performed in study.

Findings:

The study found variation in PHC population coverage (10 788–74 702) and OPD visits per day (40–182) across PHC. Strong positive association was observed between levels of laboratory services and number of OPD visits per day in PHC. PHC offering both malaria and tuberculosis in-house testing had higher odds (4.81) of getting more OPDs (≥ 80 OPD visits per day) as compared to PHC not offering in-house testing facility for malaria and tuberculosis. This association was stronger in PHCs with lower population coverage (0–75 quartile) as compared to PHCs with higher population coverage (75–100 quartile).

Conclusion:

Focus on laboratory services is needed to enhance the existing PHCs performance. Skill-up gradation of existing LT could help in improving the contribution of the existing laboratories in PHC functioning.
Nowcasting and Predicting the Kp Index Using Historical Values and Real‐Time Observations
Authors: Shprits Yuri Y. , Vasile Ruggero , Zhelavskaya Irina S.
Published: July 2019

Current algorithms for the real‐time prediction of the Kp index use a combination of models empirically driven by solar wind measurements at the L1 Lagrange point and historical values of the index. In this study, we explore the limitations of this approach, examining the forecast for short and long lead times using measurements at L1 and Kp time series as input to artificial neural networks. We explore the relative efficiency of the solar wind‐based predictions, predictions based on recurrence, and predictions based on persistence. Our modeling results show that for short‐term forecasts of approximately half a day, the addition of the historical values of Kp to the measured solar wind values provides a barely noticeable improvement. For a longer‐term forecast of more than 2 days, predictions can be made using recurrence only, while solar wind measurements provide very little improvement for a forecast with long horizon times. We also examine predictions for disturbed and quiet geomagnetic activity conditions. Our results show that the paucity of historical measurements of the solar wind for high Kp results in a lower accuracy of predictions during disturbed conditions. Rebalancing of input data can help tailor the predictions for more disturbed conditions.
Progressive Growth of the Cerro Bayo Cryptodome, Chachahuén Volcano, Argentina—Implications for Viscous Magma Emplacement
Authors: Burchardt Steffi , Mattsson Tobias , Palma J. Octavio , Galland Olivier , Almqvist Bjarne , Mair Karen , Jerram Dougal A. , Hammer Øyvind , Sun Yang
Published: July 2019

Cryptodome and dome collapse is associated with volcanic hazards, such as explosive eruptions, pyroclastic density currents, and volcanic edifice collapse. The study of the growth and evolution of volcanic domes provides vital information on the link between dome growth and the development of weakness zones that may cause collapse. The Cerro Bayo cryptodome is superbly exposed in the eroded Miocene Chachahuén volcano in the Neuquén basin, Argentina. Cerro Bayo is a >0.3‐km3 trachyandesitic cryptodome that intruded within the uppermost kilometer of the Chachahuén volcano. Here we investigate the emplacement of the Cerro Bayo cryptodome using structural mapping, photogrammetry and measurement of magma flow indicators, brittle deformation features, and magnetic fabrics with anisotropy of magnetic susceptibility. Magma flow fabrics near the margin are concentric and indicate contact‐parallel flow and internal inflation of the body. Magmatic and magnetic fabrics and fracture patterns in the interior of the cryptodome are more complex and outline several structural domains. These domains are separated by magmatic shear zones that accommodated intrusion growth. The shear zones locally overprint the earlier formed concentric fabric. The nature of the structural domains shows that the emplacement of Cerro Bayo occurred in three stages that resemble the endogenous to exogenous growth of volcanic domes. The formation of magmatic shear zones during cryptodome formation may have a profound effect on cryptodome stability by creating weakness zones that increase the risk of collapse.
Revisiting Snow Cover Variability and Canopy Structure Within Forest Stands: Insights From Airborne Lidar Data
Authors: Mazzotti Giulia , Currier William Ryan , Deems Jeffrey S. , Pflug Justin M. , Lundquist Jessica D. , Jonas Tobias
Published: July 2019

The retrieval of detailed, co‐located snow depth and canopy cover information from airborne lidar has advanced our understanding of links between forest snow distribution and canopy structure. In this study, we present two recent high‐resolution (1 m) lidar data sets acquired in (i) a 2017 mission in the Eastern Swiss Alps and (ii) NASA's 2017 SnowEx field campaign at Grand Mesa, Colorado. Validation of derived snow depth maps against extensive manual measurements revealed a RMSE of 6 and 3 cm for plot‐level mean and standard deviation of snow depth, respectively, demonstrating that within‐stand snow distribution patterns were captured reliably. Lidar data were further processed to obtain canopy structure metrics. To this end, we developed a novel approach involving a continuous measure of local distance to canopy edge (DCE), which enabled creating spatially aggregated nondirectional and directional descriptors of the canopy structure. DCE‐based canopy metrics were correlated to mean and standard deviation of snow depth over areas representing grid‐cell sizes typical of watershed and regional model applications (20–200 m). Snow depth increased along the DCE gradient from dense canopy to the center of canopy gaps for all sites and acquisition times, while directional effects particularly evolved during the ablation season. These findings highlight the control of canopy gap distribution on snow distribution in discontinuous forests, with higher snow depths where the open fraction is concentrated in few large gaps rather than many fragmented small gaps. In these environments, dedicated canopy structure metrics such as DCE should advance spatially distributed snow modeling.
On the Effect of Nonlinear Recessions on Low Flow Variability: Diagnostic of an Analytical Model for Annual Flow Duration Curves
Authors: Karst Nathaniel , Dralle David , Müller Marc F.
Published: July 2019

Predicting the proportion of the water year a given stream will remain at or above various flow thresholds is critically important for making sound water management decisions. Flow duration curves (FDCs) succinctly capture this information using all data available over some historical period, while annual flow duration curves (AFDCs) instead use data from each individual water year. Analyzing the population of AFDCs, and in particular the tails of this distribution, can allow water managers to better prepare for years with extreme streamflow conditions. However, long time series of observations are necessary to capture interannual streamflow variations and are problematic to obtain in rapidly changing and poorly gauged catchments. By incorporating a process‐based model to construct AFDCs based on daily rainfall statistics and flow recession characteristics, the proposed approach is a first step toward addressing this challenge. Results indicate that prediction performance varies substantially across flow quantiles and that the current model fails to properly capture the interannual variability of low flows. Numerical analyses attributed these errors to nonlinearity in storage‐discharge relation, rather than cross‐scale streamflow correlations and non‐Poissonian rainfall, explaining the origin of commonly observed heavy‐tailed behavior in low flow quantiles. We present a case study on hydroelectric power generation, showing that faithfully capturing both interannual streamflow variability and recession nonlinearity has important implications for installation profitability.
High‐Resolution Snowline Delineation From Landsat Imagery to Infer Snow Cover Controls in a Himalayan Catchment
Authors: Girona‐Mata Marc , Miles Evan S. , Ragettli Silvan , Pellicciotti Francesca
Published: July 2019

The snow cover dynamics of High Mountain Asia are usually assessed at spatial resolutions of 250 m or greater, but this scale is too coarse to clearly represent the rugged topography common to the region. Higher‐resolution measurement of snow‐covered area often results in biased sampling due to cloud cover and deep shadows. We therefore develop a Normalized Difference Snow Index‐based workflow to delineate snow lines from Landsat Thematic Mapper/Enhanced Thematic Mapper+ imagery and apply it to the upper Langtang Valley in Nepal, processing 194 scenes spanning 1999 to 2013. For each scene, we determine the spatial distribution of snow line altitudes (SLAs) with respect to aspect and across six subcatchments. Our results show that the mean SLA exhibits distinct seasonal behavior based on aspect and subcatchment position. We find that SLA dynamics respond to spatial and seasonal trade‐offs in precipitation, temperature, and solar radiation, which act as primary controls. We identify two SLA spatial gradients, which we attribute to the effect of spatially variable precipitation. Our results also reveal that aspect‐related SLA differences vary seasonally and are influenced by solar radiation. In terms of seasonal dominant controls, we demonstrate that the snow line is controlled by snow precipitation in winter, melt in premonsoon, a combination of both in postmonsoon, and temperature in monsoon, explaining to a large extent the spatial and seasonal variability of the SLA in the upper Langtang Valley. We conclude that while SLA and snow‐covered area are complementary metrics, the SLA has a strong potential for understanding local‐scale snow cover dynamics and their controlling mechanisms.
Using Biotic Interaction Networks for Prediction in Biodiversity and Emerging Diseases
Authors: Stephens Christopher , Giménez Heau Joaquin , González-Rosas Camila , Ibarra-Cerdeña Carlos , Sánchez-Cordero Victor
Published: July 2019

Networks offer a powerful tool for understanding and visualizing inter-species interactions within an ecology. Previously considered examples, such as trophic networks, are just representations of experimentally observed direct interactions. However, species interactions are so rich and complex it is not feasible to directly observe more than a small fraction. In this paper, using data mining techniques, we show how potential interactions can be inferred from geographic data, rather than by direct observation. An important application area for such a methodology is that of emerging diseases, where, often, little is known about inter-species interactions, such as between vectors and reservoirs. Here, we show how using geographic data, biotic interaction networks that model statistical dependencies between species distributions can be used to infer and understand inter-species interactions. Furthermore, we show how such networks can be used to build prediction models. For example, for predicting the most important reservoirs of a disease, or the degree of disease risk associated with a geographical area. We illustrate the general methodology by considering an important emerging disease - Leishmaniasis. This data mining approach allows for the use of geographic data to construct inferential biotic interaction networks which can then be used to build prediction models with a wide range of applications in ecology, biodiversity and emerging diseases.
Young children do not integrate visual and haptic information
Authors: Gori Monica , Del Viva Michela , Sandini Giulio , Burr David
Published: July 2019

Several studies have shown that adults integrate visual and haptic information (and information from other modalities) in a statistically optimal fashion, weighting each sense according to its reliability. To date no studies have investigated when this capacity for cross-modal integration develops. Here we show that prior to eight years of age, integration of visual and haptic spatial information is far from optimal, with either vision or touch dominating totally, even in conditions where the dominant sense is far less precise than the other (assessed by discrimination thresholds). For size discrimination, haptic information dominates in determining both perceived size and discrimination thresholds, while for orientation discrimination vision dominates. By eight-ten years, the integration becomes statistically optimal, like adults. We suggest that during development, perceptual systems require constant recalibration, for which cross-sensory comparison is important. Using one sense to calibrate the other precludes useful combination of the two sources.
M. tuberculosis interactome analysis unravels potential pathways to drug resistance
Authors: Raman Karthik , Chandra Nagasuma
Published: July 2019

Drug resistance is a major problem for combating tuberculosis. Lack of understanding of how resistance emerges in bacteria upon drug treatment limits our ability to counter resistance. By analysis of the Mycobacterium tuberculosis interactome network, along with drug-induced expression data from literature, we show possible pathways for the emergence of drug resistance. To a curated set of resistance related proteins, we have identified sets of high propensity paths from different drug targets. Many top paths were upregulated upon exposure to anti-tubercular drugs. Different targets appear to have different propensities for the four resistance mechanisms. Knowledge of important proteins in such pathways enables identification of appropriate 'co-targets', which when simultaneously inhibited with the intended target, is likely to help in combating drug resistance. RecA, Rv0823c, Rv0892 and DnaE1 were the best examples of co-targets for combating tuberculosis. This approach is also inherently generic, likely to significantly impact drug discovery.
Circadian rhythmic kinase CK2α phosphorylates BMAL1 to regulate the mammalian clock
Authors: Tamaru Teruya , Hirayama Jun , Isojima Yasushi , Nagai Katsuya , Norioka Shigemi , Takamatsu Ken , Sassone-Corsi Paolo
Published: July 2019

Clock proteins govern circadian physiology and their function is regulated by a variety of signaling pathways. Here, we show that p45^PFK^, a previously reported circadian rhythmic kinase, corresponds to CK2[alpha]. Rhythmic phosphorylation of the core clock protein BMAL1 by CK2[alpha] occurs in the suprachiasmatic nuclei (SCN), the mammalian central pacemaker. Circadian BMAL1 phosphorylation controls its nucleocytoplasmic localization. Gene silencing for CK2[alpha] and BMAL1 mutagenesis of a highly conserved CK2 phosphorylation site (Ser 90) result in impaired BMAL1 accumulation in the nucleus and subsequent disruption of clock function. These findings reveal that circadian rhythmic kinase CK2 is an essential regulator of the mammalian circadian system.