bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study*
Authors: Compher Charlene , Chittams Jesse , Sammarco Therese , Nicolo Michele , Heyland Daren K.
Published: January 2017

Objectives:

Controversy exists about the value of greater nutritional intake in critically ill patients, possibly due to varied patient nutritional risk. The objective of this study was to investigate whether clinical outcomes vary by protein or energy intake in patients with risk evaluated by the NUTrition Risk in the Critically Ill score.

Design:

Prospective observational cohort.

Setting:

A total of 202 ICUs.

Patients:

A total of 2,853 mechanically ventilated patients in ICU greater than or equal to 4 days and a subset of 1,605 patients in ICU greater than or equal to 12 days.

Interventions:

None.

Measurements and Main Results:

In low-risk (NUTrition Risk in the Critically Ill, < 5) and high-risk (NUTrition Risk in the Critically Ill, ≥ 5) patients, mortality and time to discharge alive up to day 60 were assessed relative to nutritional intake over the first 12 days using logistic regression and Cox proportional hazard regression, respectively. In high-risk but not low-risk patients, mortality was lower with greater protein (4-d sample: odds ratio, 0.93; 95% CI, 0.89–0.98; p = 0.003 and 12-d sample: odds ratio, 0.90; 95% CI, 0.84–0.96; p = 0.003) and energy (4-d sample: odds ratio, 0.93; 95% CI, 0.89–0.97; p < 0.001 and 12-d sample: odds ratio, 0.88; 95% CI, 0.83–0.94; p < 0.001) intake. In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, mortality, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant. In high-risk but not low-risk patients, time to discharge alive was shorter with greater protein (4-d sample: hazard ratio, 1.05; 95% CI, 1.01–1.09; p = 0.01 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03–1.16; p = 0.002) and energy intake (4-d sample: hazard ratio, 1.05; 95% CI, 1.01–1.09; p = 0.02 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03–1.16; p = 0.002). In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, time to discharge alive, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant.

Conclusions:

Greater nutritional intake is associated with lower mortality and faster time to discharge alive in high-risk, longer stay patients but not significantly so in nutritionally low-risk patients.
Vision-Related Quality of Life Before and After Deep Anterior Lamellar Keratoplasty
Authors: Yildiz Elvin , Toklu Meltem , Turan Vural Ece
Published: January 2017

Objectives:

To determine changes in the vision-related quality of life in patients undergoing deep anterior lamellar keratoplasty (DALK) by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

Methods:

Thirty-five patients who were scheduled for DALK between March 1, 2013, and March 1, 2014 were asked to complete the NEI VFQ-25. NEI VFQ-25 was administered again at 6 months and at 1 year postoperatively. Data on patients' age, sex, preoperative diagnosis, preoperative and postoperative best-corrected visual acuity, and postoperative astigmatism were recorded.

Results:

Successful DALK with the Anwar big bubble technique was achieved in 23 of 35 (65.7%) patients. The indications for surgery were keratoconus in 15 patients (62.2%), stromal corneal dystrophies in 4 (17%), and corneal scar in 4 (17%). The mean preoperative NEI VFQ-25 composite score (55.2±19.7) improved significantly (76.9±11.6) at 6 months after DALK and continued to improve (84.3±6.6) at 1 year postoperatively (Friedman test, P=0.001). All NEI VFQ-25 subscale item scores increased significantly after surgery. The patients' age was significantly correlated with the NEI VFQ-25 subscale score of mental health at 6 month and at 1 year postoperatively (r=0.92, P=0.008 and r=0.94, P=0.005, respectively). There was a negative relationship between postoperative astigmatism at 1 year and NEI VFQ-25 ocular pain, social functioning, peripheral vision, and mental health subscale scores (r=−0.76, P=−0.07; r=−0.53, P=0.2; r=−0.53, P=0.27; r=−0.80, P=0.05).

Conclusion:

Vision-related quality of life improved significantly after DALK and continued to improve after suture removal.
The Characteristics of Excimer Laser Refractive Surgery Candidates
Authors: Hashemi Hassan , Khabazkhoob Mehdi , Pakzad Reza , Yekta Abbasali , Nojomi Marzieh , Nabovati Payam
Published: January 2017

Purpose:

To determine the demographic and refractive characteristics of excimer laser refractive surgery candidates in Iran.

Methods:

This was a cross-sectional study between 2010 and 2014. All information was collected from 28 centers randomly selected from 12 provinces. Then, for each season of the year, one week was chosen through simple random selection, and within each week, 3 days were again chosen randomly. All excimer laser surgical procedures performed during these 3 days were identified by training staff, and data were extracted from patient charts.

Results:

A total of 14,569 charts were reviewed; 67.5% of the subjects were female and the rest were male. Of the total surgeries, 18.6% had been done in 2010 which reached to 19.1% in 2014. The mean age of people receiving refractive surgery showed an upward trend (P<0.001) and female patients were significantly younger than male patients (P<0.001). The 25 to 39 years age group received the highest number of surgeries (31.9% of the total) and there was a significant association with gender (P<0.001). The most common refractive error was compound myopic astigmatism with a prevalence of 79.3%. In 2010, 33.3% of the performed surgeries were covered by insurance policies, and this decreased to 30.2% in 2014 (P<0.001).

Conclusion:

Women with compound myopic astigmatism in the age range of 25 and 35 years are the most frequent users of excimer laser refractive surgery. Less than one-third of laser refractive surgeries are covered by insurance policies. Therefore, proper planning for improving services to this group must be given priority.
A Novel Treatment using an Intraventricular Stent Graft for Postinfarction Ventricular Septal Rupture in a Porcine Model
Authors: Nishida Yuji , Tomita Shigeyuki , Kiuchi Ryuta , Ohtake Hiroshi , Watanabe Go
Published: January 2017

Objective

Ventricular septal rupture (VSR) is a severe complication of acute myocardial infarction, and the conventional technique for repair is associated with high operative mortality. A novel intraventricular stent graft (IVSG) device was tested as a less invasive treatment for VSR; it does not require cardiopulmonary bypass, cardiac arrest, or left ventricular incision. Its effectiveness was assessed using animal experiments.

Methods

Six pigs were placed on cardiopulmonary bypass. The VSR model was created by making a hole in the interventricular septum via the right ventricle. Animals were weaned off the bypass. The sheath encasing the device was advanced over the guidewire, and the IVSG was placed in the left ventricle. Before and after rupture creation and after device deployment, left ventriculography was performed, hemodynamic data were collected, and Qp/Qs values were measured.

Results

All procedures were completed safely. The left-to-right shunt seen after rupture creation disappeared after device deployment. The pulmonary-to-systemic blood flow ratio after rupture was 3.35 ± 1.00, decreasing significantly to 1.09 ± 0.10 after device deployment (P = 0.007). Hemodynamic instability after rupture creation improved dramatically after deployment.

Conclusions

The use of our new IVSG in this VSR animal experiment model significantly decreased the left-to-right shunt. The new device was able to control the acute heart failure associated with VSR with a minimally invasive procedure during the hyperacute phase of heart failure. Potential improvements in VSR treatment outcomes are expected with its clinical application.
Noninvasive Quantification of Blood Flow in Epicardial Coronary Arteries, Coronary Artery Bypass Grafts, and Anastomoses
Authors: Ferguson T. Bruce , Chen Cheng , Kim Sunghan , Jacobs Kenneth , Peng Zhiyong , Zhu Zhen , Buch Ashesh N. , Basham Jeffery C.
Published: January 2017

Objective

Direct flow measurement in native epicardial coronary arteries, bypass conduits, and anastomoses is severely limited by the invasiveness and inaccuracy of existing technologies. As a result, less than 25% of patients undergoing coronary artery bypass grafting (CABG) worldwide have any intraoperative evaluation performed. A simple, accurate, and noninvasive technology to directly quantify blood flow and rheology surrounding anastomotic sites is a critical unmet need in CABG.

Methods

Existing technology limitations drove development of a different technology solution. With an optical physics approach, flow in conduits and tissue can be quantified in real time with nonionizing broad-spectrum imaging as well as temporal and spatial analyses. Cardiac motion, calibration, and combining anatomy + physiology in imaging were challenges requiring solutions.

Results

This patented imaging technology was developed and tested in an established porcine cardiac experimental model and in clinical proof-of-concept studies. Flow velocities and flows in epicardial coronary arteries vary physiologically with the cardiac cycle and with acute ischemia, as predicted by previous studies using traditional technologies. Imaging data are captured from a 30-cm viewing distance, analyzed and displayed in real time as a video. The field of view enables capture of flow in the proximal and distal epicardial coronary, the conduit, at the anastomosis and in the distal myocardium simultaneously.

Conclusions

Rheologic flow interaction between conduit and native coronary at the anastomosis remains the most poorly understood technical aspect of CABG. A noninvasive, noncontact, no-risk imaging technology as simple as a snapshot can provide this critical physiologic information, validate and document intraoperative quality, and improve even further CABG outcomes.
Poststroke depression: risk factors and potential effects on functional recovery
Authors: Karaahmet Ozgur Z. , Gurcay Eda , Avluk Ozlem C. , Umay Ebru K. , Gundogdu Ibrahim , Ecerkale Oznur , Cakci Aytul
Published: January 2017

The factors that may cause poststroke depression were investigated in the literature focusing on lesion localization, age, stroke severity, and impairments in physical and cognitive function. The aim of this study was to examine the risk factors influencing the development of poststroke depression and to determine the effect of depression on the patients’ functional improvement after rehabilitation. Patients in the first 6-month period after stroke who were hospitalized in the Physical Medicine and Rehabilitation Clinic were included in this study. Patients who were admitted to the hospital within 0–30 and 30–120 days from the date of stroke were considered early and late rehabilitation entrants, respectively. The sample of this study included 93 patients. Patients’ demographic and clinical characteristics, complications, and medical history were recorded. Upper extremity motor function, ambulation, and mood were evaluated according to the Frenchay Arm Test, the Functional Ambulation Scale, and the Beck Depression Inventory, respectively. The Functional Independence Measure (FIM) was applied to patients at admission to the hospital, at discharge, and 1 month after discharge (follow-up). The mean age of the patients was 58 years and the mean disease duration was 53 days. Depression was diagnosed in 49 (53%) patients. Except for age and disease duration, none of the factors of sex, hemiplegic side, stroke severity, stroke etiology, neglect, spasticity, sedentary lifestyle, poststroke immobility, and early-onset or late-onset to rehabilitation was found to induce statistically significant differences in the development of depression. Statistically significant changes occurred in total FIM levels between the groups with and without depression between admission and discharge, admission and follow-up, and discharge and follow-up. The levels were significantly higher in patients without depression than in patients with depression. Depression was found in a high frequency in stroke patients. Younger age and long disease duration were found to be factors affecting the development of depression. FIM scores were observed to be lower in stroke patients with depression.
Validating a Clinical Prediction Rule for Ventricular Shunt Malfunction
Authors: Boyle Tehnaz P. , Kimia Amir A. , Nigrovic Lise E.
Published: January 2017

Objective

This study aims to validate a published ventricular shunt clinical prediction rule for the identification of children at low risk for ventricular shunt malfunction based on the absence of 3 high-risk clinical predictors (irritability, nausea or vomiting, and headache).

Methods

We identified children aged 21 years and younger with a ventricular shunt who presented between 2010 and 2013 to a single pediatric emergency department (ED) for evaluation of potential shunt malfunction. We defined a ventricular shunt malfunction as obstruction to cerebrospinal fluid flow requiring operative neurosurgical intervention within 72 hours of initial ED evaluation. We applied this ventricular shunt clinical prediction rule to the study population and report the test characteristics.

Results

We identified 755 ED visits for 294 children with potential ventricular shunt malfunction. Of these encounters, 146 (19%; 95% confidence interval [CI], 17%–22%) had a ventricular shunt malfunction. The ventricular shunt clinical prediction rule had a sensitivity of 99% (95% CI, 94%–100%), specificity of 7% (95% CI, 5%–9%), and negative predictive value of 95% (95% CI, 82%–99%). Two children with a ventricular shunt malfunction were misclassified as low risk by this clinical prediction rule.

Conclusions

Ventricular shunt malfunctions were common. Although children classified as low risk by the ventricular shunt clinical prediction rule were less likely to have a shunt malfunction, routine neuroimaging may still be required because exclusion of ventricular shunt malfunction may be difficult on clinical grounds alone.
Comparing the Outcomes of Reporting and Trigger Tool Methods to Capture Adverse Events in the Emergency Department
Authors: Lee Wen-Huei , Zhang Ewai , Chiang Charng-Yen , Yen Yung-Lin , Chen Ling-Ling , Liu Mei-Hsiu , Kung Chia-Te , Hung Shih-Chiang
Published: January 2017

Background

Little is known about which methods are best for detecting adverse events in the emergency department (ED).

Objectives

This study compared the ability of trigger tool and reporting methods to capture adverse events in the ED and investigated the characteristics of the adverse events identified by each.

Methods

This 1-year prospective observational cohort study evaluated a monitoring system that combined 2 reporting methods and 5 trigger tool methods to capture adverse events in the ED of an academic medical center. Measurement outcomes included the number, type, and physical impact of the captured adverse events.

Results

Among 69,327 adult nontrauma ED visits, 285 adverse events were identified. Of these adverse events, 77.2% were identified using reporting methods, 26% using trigger tool methods, and 3.2% using both methods. Most patients (81.7%) incurred temporary, minor physical impacts. Of the adverse events that occurred, 86.7% were related to clinical performance. Compared with reporting methods, trigger tool methods had a lower positive predictive rate to identify adverse events (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.09–0.16), a greater proportion of adverse events occurring during the preinterventation and postintervention phases (OR, 17.0; 95% CI, 8.48–34.16), and more cases of severe physical impact or death (OR, 5.4; 95% CI, 2.62–11.10).

Conclusions

The reporting methods more effectively captured greater numbers of adverse events, whereas the adverse events captured by the trigger tool methods were more likely to be severe physical impacts. The combined use of the different methods had synergistic benefits for monitoring adverse events in the ED.
Testing for departure from uniformity and estimating mean direction for circular data
Authors: Ruxton Graeme D.
Published: January 2017

Although circular data are common in biological studies, the analysis of such data is often more rudimentary than it need be. One of the most common hypotheses tested is whether the data suggest that samples are clustered around a certain specified direction, rather than being uniformly spread across all possible directions. Here, I use data from a recent publication on the compass directions of epiphytes and mistletoes on tree trunks. This is used to demonstrate how with relatively little extra work researchers can improve the rigour of testing such hypotheses, and this improved rigour can lead to biological insights missed by simpler analyses. Specifically, I highlight that a much broader range of null hypotheses can be tested than current practice, and that a range of methods are available for estimating a confidence interval for mean direction. I offer advice on appropriate selection for both tests and parameter estimation methods, and highlight the need to correct for the fact that sample estimates are biased estimates of population parameters for circular data.
Biomechanical properties of wheat grains: the implications on milling
Authors: Hourston James E. , Ignatz Michael , Reith Martin , Leubner-Metzger Gerhard , Steinbrecher Tina
Published: January 2017

Millennia of continuous innovation have driven ever increasing efficiency in the milling process. Mechanically characterizing wheat grains and discerning the structure and function of the wheat bran layers can contribute to continuing innovation. We present novel shear force and puncture force testing regimes to characterize different wheat grain cultivars. The forces endured by wheat grains during the milling process can be quantified, enabling us to measure the impact of commonly applied grain pretreatments, such as microwave heating, extended tempering, enzyme and hormone treatments on grains of different ‘hardness’. Using these methods, we demonstrate the importance of short tempering phases prior to milling and identify ways in which our methods can detect differences in the maximum force, energy and breaking behaviours of hard and soft grain types. We also demonstrate for the first time, endosperm weakening in wheat, through hormone stratification on single bran layers. The modern milling process is highly refined, meaning that small, cultivar specific, adjustments can result in large increases in downstream profits. We believe that methods such as these, which enable rapid testing of milling pretreatments and material properties can help to drive an innovation process that has been core to our industrial efforts since prehistory.
Reporting correct p-values in VEGAS analyses
Authors: Hecker Julian , Maaser Anna , Prokopenko Dmitry , Fier Heide Loehlein , Lange Christoph
Published: January 2017

VEGAS (versatile gene-based association study) is a popular methodological framework to perform gene-based tests based on summary statistics from single-variant analyses. The approach incorporates linkage disequilibrium information from reference panels to account for the correlation of test statistics. The gene-based test can utilize three different types of tests. In 2015, the improved framework VEGAS2, using more detailed reference panels, was published. Both versions provide user-friendly web- and offline-based tools for the analysis. However, the implementation of the popular top-percentage test is erroneous in both versions. The p-values provided by VEGAS2 are deflated/anti-conservative. Based on real data examples, we demonstrate that this can increase substantially the rate of false positive findings and can lead to inconsistencies between different test options. We also provide code that allows the user of VEGAS to compute correct p-values.
HeterozygousRFX6protein truncating variants are associated with Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance
Authors: Patel Kashyap A , Kettunen Jarno , Laakso Markku , Stančáková Alena , Laver Thomas W , Colclough Kevin , Johnson Matthew B. , Abramowicz Marc , Groop Leif , Miettinen Päivi J. , Shepherd Maggie H , Flanagan Sarah E , Ellard Sian , Inagaki Nobuya , Hattersley Andrew T , Tuomi Tiinamaija , Cnop Miriam , Weedon Michael N
Published: January 2017

Finding new genetic causes of monogenic diabetes can help to understand development and function of the human pancreas. We aimed to find novel protein–truncating variants causing Maturity–Onset Diabetes of the Young (MODY), a subtype of monogenic diabetes. We used a combination of next–generation sequencing of MODY cases with unknown aetiology along with comparisons to the ExAC database to identify new MODY genes. In the discovery cohort of 36 European patients, we identified two probands with novelRFX6heterozygous nonsense variants.RFX6protein truncating variants were enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio, OR=131, P=l×l0‐4). We found similar results in non–Finnish European (n=348, OR=43, P=5×l0‐5) and Finnish (n=80, OR=22, P=1×l0‐6) replication cohorts. The overall meta–analysis OR was 34 (P=l×l0‐16).RFX6heterozygotes had reduced penetrance of diabetes compared to commonHNF1AandHNF4A–MODY mutations (27%, 70% and 55% at 25 years of age, respectively). The hyperglycaemia resulted from beta–cell dysfunction and was associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygousRFX6protein truncating variants are associated with MODY with reduced penetrance.
Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting
Authors: Fraize Nicolas , Hamieh Al Mahdy , Joseph Mickaël Antoine , Touret Monique , Parmentier Régis , Salin Paul Antoine , Malleret Gaël
Published: January 2017

Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference. To determine the role of CaMKII and GluA1 in adaptive forgetting, we adopted a comparative approach to assess the relative quantity and phosphorylation state of these proteins in the brain of rats trained in one of three radial maze paradigms: a RM task, a WM task involving a high level of adaptive forgetting, or a WM involving a low level of adaptive forgetting. Surprisingly, Western blot analyses revealed that training in a WM task involving a high level of adaptive forgetting specifically increased the expression of AMPA receptor GluA1 subunit and the activity of CaMKII in the dentate gyrus. These results highlight that WM with proactive interference involves mechanisms of synaptic plasticity selectively in the dentate gyrus.
Kaizen within Kaizen Teams: Continuous and Process Improvements in a Spanish municipality
Authors: Suárez‐Barraza1 Manuel F. , Lingham Tony
Published: January 2017

Purpose

As organizations become more team oriented, research on teams continues to increase especially involving how teams contribute to organizational performance and effectiveness. Although there has been existing research on Kaizen teams in the private sector, very little research has included Kaizen teams in the public sector. In this paper, we present a method to study Kaizen teams in a local Spanish government that have been using Kaizen teams for more than ten years.

Design/methodology/approach

Quantitative research was adopted for this study. Twenty teams participated in the study by filling out the Team Learning and Development Inventory (TLI) proposed by Lingham (2004). In addition, we interviewed members of the teams in
order to clarify and assure our quantitative results.

Findings

Based on the findings, we propose that Kaizen teams should practice both Continuous (CI) and Process Improvements (PI) in their projects. We also propose that Kaizen teams should not be teams skilled only at developing better improvement processes (both CI and PI) for the organization but that such teams should also be skilled at engaging in team development using both CI and PI processes internally – a Kaizen within Kaizen teams approach.

Research limitations

Its based in one case study. However, it is working paper and the research project still is developing.

Practical Implications

Serve as a guide to practitioners (Public managers) who desire to understand how their Kaizen teams involves both internal (conversational spaces) and external (methodology) perspectives that would contribute to both team and organizational effectiveness. In this paper, we focus on the Internal Processes (both CI and PI) using the TLI as an effective method for Kaizen teams to engage in the Kaizen process.

Originality/value

This study is one of the first to look at team’s performance using Team Learning and Development Inventory in Spain’s public sector. It is also the first to mention about the relationship of the team’s performance and the implementation of process improvement methodologies in Spain local government environment.
Gastronomy management
Authors: Bernardo Merce , Escalante Raúl , Roca Joan , Arbussà Anna
Published: January 2017

Purpose

The purpose of this paper is to analyze and compare the existing management system standards in the gastronomy sector.

Design/methodology/approach

On the basis of secondary data, the most implemented management system standards within this sector are analyzed, namely, the ISO 9001 focusing on the sector of “hotels and restaurants,” the ISO 22000, the “Q” Spanish tourism-specific standard, and the Michelin stars system.

Findings

The results, although descriptive, show the differences among them. Regarding the content, the main difference between the documented management system standards and the Michelin stars system is in the evaluation and certification process, as it is known and planned in the former group but not in the latter. The scope is also different, as the former group refers mainly to the process and the latter to results. The diffusion results confirm the increase in sectoral management system standards.

Originality/value

Although studies analyzing the importance of sectoral standards have been published, this study is one of the first focusing on four different management system standards in the gastronomy sector. Implications for both practitioners and academia are also discussed.
Enhancement of ester formation in Camembert cheese by addition of ethanol
Authors: Hong Qing , Wang Gang , Zhang Qiuxiang , Tian Fengwei , Xiao‐Ming Liu , Zhao Jianxin , Chen Yong‐Quan , Zhang Hao , Chen Wei
Published: January 2017

Ethyl esters are often detected at trace levels in Camembert cheese. This study investigated how the addition of ethanol prior to cheesemaking influenced the composition, texture and flavour profile of Camembert compared to a control cheese manufactured under identical conditions without ethanol. No statistical differences were observed in the composition, microbes or textures of the experimental and control cheeses. However, more ethyl esters and a significantly enhanced fruity flavour perception were reported for the experimental cheeses compared to the control. The addition of 400–1200 μg/g of ethanol may be applied in the production of Camembert cheese to enhance fruity flavour.
Hospital Variation in Utilization of Life‐Sustaining Treatments among Patients with Do Not Resuscitate Orders
Authors: Walkey Allan J. , Weinberg Janice , Wiener Renda Soylemez , Cooke Colin R. , Lindenauer Peter K.
Published: January 2017

Objective

To determine between‐hospital variation in interventions provided to patients with do not resuscitate (DNR) orders.

Data Sources/Setting

United States Agency of Healthcare Research and Quality, Healthcare Cost and Utilization Project, California State Inpatient Database.

Study Design

Retrospective cohort study including hospitalized patients aged 40 and older with potential indications for invasive treatments: in‐hospital cardiac arrest (indication for CPR), acute respiratory failure (mechanical ventilation), acute renal failure (hemodialysis), septic shock (central venous catheterization), and palliative care. Hierarchical logistic regression to determine associations of hospital “early” DNR rates (DNR order placed within 24 hours of admission) with utilization of invasive interventions.

Data Collection/Extraction Methods

California State Inpatient Database, year 2011.

Principal Findings

Patients with DNR orders at high‐DNR‐rate hospitals were less likely to receive invasive mechanical ventilation for acute respiratory failure or hemodialysis for acute renal failure, but more likely to receive palliative care than DNR patients at low‐DNR‐rate hospitals. Patients without DNR orders experienced similar rates of invasive interventions regardless of hospital DNR rates.

Conclusions

Hospitals vary widely in the scope of invasive or organ‐supporting treatments provided to patients with DNR orders.
A systematic review and meta‐analysis of prospective transition from major depression to bipolar disorder
Authors: Ratheesh A. , Davey C. , Hetrick S. , Alvarez‐Jimenez M. , Voutier C. , Bechdolf A. , McGorry P. D. , Scott J. , Berk M. , Cotton S. M.
Published: January 2017

Objective

Some people with major depressive disorder (MDD) may be at a pre‐onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow‐up studies of people with MDD.

Methods

Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow‐up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors.

Results

From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12–18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta‐analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01–4.14, N = 7), earlier age of onset of depression (g = −0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79–12.66, N = 5).

Conclusions

Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.
Deletion of 2.7 kb near HOXD3 in an Arabian horse with occipitoatlantoaxial malformation
Authors: Bordbari M. H. , Penedo M. C. T. , Aleman M. , Valberg S. J. , Mickelson J. , Finno C. J.
Published: January 2017

In the horse, the term occipitoatlantoaxial malformation (OAAM) is used to describe a developmental defect in which the first cervical vertebra (atlas) resembles the base of the skull (occiput) and the second cervical vertebra (axis) resembles the atlas. Affected individuals demonstrate an abnormal posture and varying degrees of ataxia. The homeobox (HOX) gene cluster is involved in the development of both the axial and appendicular skeleton. Hoxd3‐null mice demonstrate a strikingly similar phenotype to Arabian foals with OAAM. Whole‐genome sequencing was performed in an OAAM‐affected horse (OAAM1) and seven unaffected Arabian horses. Visual inspection of the raw reads within the region of HOXD3 identified a 2.7‐kb deletion located 4.4 kb downstream of the end of HOXD4 and 8.2 kb upstream of the start of HOXD3. A genotyping assay revealed that both parents of OAAM1 were heterozygous for the deletion. Additional genotyping identified two of 162 heterozygote Arabians, and the deletion was not present in 371 horses of other breeds. Comparative genomics studies have revealed that this region is highly conserved across species and that the entire genomic region between Hoxd4 and Hoxd3 is transcribed in mice. Two additional Arabian foals diagnosed with OAAM (OAAM 2 and 3) were genotyped and did not have the 2.7‐kb deletion. Closer examination of the phenotype in these cases revealed notable variation. OAAM3 also had facial malformations and a patent ductus arteriosus, and the actual malformation at the craniocervical junction differed. Genetic heterogeneity may exist across the HOXD locus in Arabian foals with OAAM.
Individual Creativity during the Ideation Phase of Product Innovation: An Interactional Perspective
Authors: Guo Jing , Su Qin , Zhang Qian
Published: January 2017

Although there is increasing acknowledgement that employees' creative ideas are fundamental for product innovation, and many companies use cross‐functional teams to increase employee creativity, there has been little empirical testing of how individual personality and group context interactively affect individual creativity. The purpose of this study is threefold: to examine the relationship between personality and individual creativity; to assess how this relationship interacts with group diversity; and to determine whether the interaction effects between personality traits and gender diversity are mediated by individual knowledge sharing. The results of an experiment based on a sample of 142 working adults show that openness to experience and extraversion are positively related to individual creativity, whereas neuroticism and conscientiousness are negatively related to individual creativity. Furthermore, the impacts of openness to experience and extraversion on individual creativity, respectively, are moderated by both functional diversity and gender diversity. In addition, these interaction effects are mediated by individual knowledge sharing. Interestingly, this study also finds that the direction of functional diversity's moderating effects depends on the level of group diversity.
Methodological quality, completeness of reporting and use of systematic reviews as evidence in clinical practice guidelines for paediatric overweight and obesity
Authors: Nissen T. , Wayant C. , Wahlstrom A. , Sinnett P. , Fugate C. , Herrington J. , Vassar M.
Published: January 2017

Paediatric obesity rates remain high despite extensive efforts to prevent and treat obesity in children. We investigated the quality of the methodology and reporting within systematic reviews (SRs) underpinning paediatric content in US clinical practice guidelines (CPGs). In June 2016 we searched guideline clearinghouses and professional organization websites for guidelines published by national or professional organizations in the United States from January 2007 onwards. In our primary, a priori analysis, we used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) instruments to score SRs and meta‐analyses that included paediatric populations and were cited by included CPGs. In a secondary, post hoc analysis, we determined the extent to which US CPGs use available, relevant SRs and meta‐analyses compared with non‐US CPGs. Eight US‐based CPGs with 27 references to 22 unique SRs were found. AMSTAR and PRISMA scores were low overall, with only three SRs having ‘high’ methodological quality. Items dealing with bias assessments and search strategies had especially low scores. US CPGs were also older on average and cited fewer SRs than their international counterparts. Low quality scores and dated guidelines should be a cause for concern among practicing clinicians and a call to action for future guideline developers, publishers and research institutions.
HIV encephalopathy with bilateral lower limb spasticity: gross motor function and antiretroviral therapy
Authors: Mann Theresa N , Laughton Barbara , Donald Kirsten A , Langerak Nelleke G
Published: January 2017

Aim

To describe gross motor function in children with bilateral lower limb (BLL) spasticity due to human immunodeficiency virus encephalopathy (HIVE), and to investigate the association between age, CD4 percentage, and viral load at initiation of antiretroviral therapy (ART) and current gross motor function.

Method

Thirty ambulant children with HIVE and BLL spasticity were recruited. Clinical parameters, including ART, were obtained from medical records. Gross motor function was assessed using the 88‐item Gross Motor Function Measure (GMFM‐88).

Results

The participant group was comprised of 14 males and 16 females (median age 8y; interquartile range [IQR] 7–11y). ART was initiated at a median age of 7 months (IQR 5–11mo) with a median CD4 percentage of 4.7% (IQR 2.3–8.0) and viral load of log10 6.0 (IQR 5.6–6.4). The median total GMFM‐88 score was 89% (IQR 78–94%), with a wide range of scores in the ‘Standing’ domain (26–97%) and ‘Walking, Running, and Jumping’ domain (8–99%). No associations were detected between age at initiation of ART, CD4 percentage, or viral load and total GMFM‐88 score.

Interpretation

Limitations in gross motor function in children with HIVE and BLL spasticity range from mild to severe. ART initiation factors were not able to predict functional status in this sample.
Dapagliflozin in patients with type 1 diabetes: Apost hoc analysis of the effect of insulin dose adjustments on 24‐hour continuously monitored mean glucose and fasting β‐hydroxybutyrate levels in a phase IIa pilot study
Authors: Henry Robert R. , Dandona Paresh , Pettus Jeremy , Mudaliar Sunder , Xu John , Hansen Lars
Published: January 2017

Aims

To investigate the effects of total daily insulin dose (TDD) reductions on 24‐hour continuously monitored mean glucose and fasting β‐hydroxybutyrate (a marker for diabetic ketosis/ketoacidosis [DKA]) levels, using patient‐level data from a 14‐day, pilot study of dapagliflozin in type 1 diabetes (T1DM).

Methods

A post hoc exploratory correlation analysis was performed to determine the relationship between change in TDD and (1) 24‐hour mean glucose, assessed by continuous glucose monitoring, and (2) fasting β‐hydroxybutyrate, in 70 patients with T1DM receiving insulin and dapagliflozin (1, 2.5, 5 or 10 mg) or placebo. The pharmacodynamic effect of dapagliflozin was estimated as a virtual “insulin dose” using 24‐hour urinary glucose excretion values and a recognized insulin‐to‐carbohydrate counting technique.

Results

Trends for correlations were observed between change in TDD and 24‐hour glucose (day 7: r = −0.264, P = .056) and β‐hydroxybutyrate (day 7: r = −0.187, P = .133; day 14: r = −0.274, P = .047). The pharmacodynamic effect of dapagliflozin 5 or 10 mg was estimated as equivalent to ~20% of baseline TDD. Higher mean and maximum β‐hydroxybutyrate levels were observed on days 7 and 14 in patients with a TDD reduction >20% vs ≤20%.

Conclusions

Over 14 days, decreasing the insulin dose diminished the glucose‐lowering effect of dapagliflozin–insulin combination therapy and increased levels of β‐hydroxybutyrate. While insulin dose adjustments should always be individualized, these analyses suggest that, as a general rule, TDD reduction in dapagliflozin‐treated patients with T1DM should not exceed 20%, to ensure glycaemic control does not deteriorate and to mitigate the potential for an increased risk of DKA.
Attentional modulation and domain‐specificity underlying the neural organization of auditory categorical perception
Authors: Bidelman Gavin M. , Walker Breya S.
Published: January 2017

Categorical perception (CP) is highly evident in audition when listeners’ perception of speech sounds abruptly shifts identity despite equidistant changes in stimulus acoustics. While CP is an inherent property of speech perception, how (if) it is expressed in other auditory modalities (e.g., music) is less clear. Moreover, prior neuroimaging studies have been equivocal on whether attentional engagement is necessary for the brain to categorically organize sound. To address these questions, we recorded neuroelectric brain responses [event‐related potentials (ERPs)] from listeners as they rapidly categorized sounds along a speech and music continuum (active task) or during passive listening. Behaviorally, listeners’ achieved sharper psychometric functions and faster identification for speech than musical stimuli, which was perceived in a continuous mode. Behavioral results coincided with stronger ERP differentiation between prototypical and ambiguous tokens (i.e., categorical processing) for speech but not for music. Neural correlates of CP were only observed when listeners actively attended to the auditory signal. These findings were corroborated by brain‐behavior associations; changes in neural activity predicted more successful CP (psychometric slopes) for active but not passively evoked ERPs. Our results demonstrate auditory categorization is influenced by attention (active > passive) and is stronger for more familiar/overlearned stimulus domains (speech > music). In contrast to previous studies examining highly trained listeners (i.e., musicians), we infer that (i) CP skills are largely domain‐specific and do not generalize to stimuli for which a listener has no immediate experience and (ii) categorical neural processing requires active engagement with the auditory stimulus.
Posterior cortex epilepsy surgery in childhood and adolescence: Predictors of long‐term seizure outcome
Authors: Ramantani Georgia , Stathi Angeliki , Brandt Armin , Strobl Karl , Schubert‐Bast Susanne , Wiegand Gert , Korinthenberg Rudolf , van Velthoven Vera , Zentner Josef , Schulze‐Bonhage Andreas , Bast Thomas
Published: January 2017

Objective

We aimed to investigate the long‐term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors.

Methods

We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)–visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri‐ or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases.

Results

At last follow‐up (mean 8 years, range 1.5–18 years), 60% patients remained seizure‐free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left‐sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence.

Significance

Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy.
Sodium selenate treatment improves symptoms and seizure susceptibility in a malin‐deficient mouse model of Lafora disease
Authors: Sánchez‐Elexpuru Gentzane , Serratosa José M. , Sánchez Marina P.
Published: January 2017

Objective

To search for new therapies aimed at ameliorating the neurologic symptoms and epilepsy developing in patients with Lafora disease.

Methods

Lafora disease is caused by loss‐of‐function mutations in either the EPM2A or EPM2B genes. Epm2a−/− and Epm2b−/− mice display neurologic and behavioral abnormalities similar to those found in patients. Selenium is a potent antioxidant and its deficiency has been related to the development of certain diseases, including epilepsy. In this study, we investigated whether sodium selenate treatment improved the neurologic alterations and the hyperexcitability present in the Epm2b−/− mouse model.

Results

Sodium selenate ameliorates some of the motor and memory deficits and the sensitivity observed with pentylenetetrazol (PTZ) treatments in Epm2b−/− mice. Neuronal degeneration and gliosis were also diminished after sodium selenate treatment.

Significance

Sodium selenate could be beneficial for ameliorating some symptoms that present in patients with Lafora disease.
A disturbance innovation hypothesis: perspectives from human and physical geography
Authors: Baird Timothy D , Chaffin Brian C , Wrathall David J
Published: January 2017

As attention to resilience grows, debates in geography have focused on the relationship between resilience and vulnerability. This discussion raises further questions that geographers may be well positioned to address: what can be done in contexts where vulnerability is desirable, or where resilience is undesirable and where innovation may be called for? Many undesirable systems are resilient, yet strategies to break resilience down and promote innovation are not often discussed. Building on perspectives from human and physical geography, we present a new hypothesis about the relationship between disturbance and innovation. This disturbance innovation hypothesis states that low and high levels of disturbance are associated with the highest levels of innovation while intermediate levels of disturbance are associated with the lowest levels of innovation. By integrating broad perspectives from geography and its related fields, we hope to spur discussion surrounding unwanted resilience, barriers to reform, and strategies for transformation.
Immature Core protein of hepatitis C virus induces an unfolded protein response through inhibition of ERAD‐L in a yeast model system
Authors: Takahashi Shota , Sato Naoko , Kikuchi Junichi , Kakinuma Hideaki , Okawa Jun , Masuyama Yukiko , Iwasa Singo , Irokawa Hayato , Hwang Gi‐Wook , Naganuma Akira , Kohara Michinori , Kuge Shusuke
Published: January 2017

The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core‐induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1–191, Core191) but not by the mature Core (aa 1–177, Core177). Interestingly, Core191 inhibits both ERAD‐L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD‐M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane. In contrast, Core177 inhibits ERAD‐M but not ERAD‐L. In addition, requirement of an unfolded protein sensor in the ER lumen suggested that inhibition of ERAD‐L is probably responsible for Core191‐dependent UPR activation. These results implicate inadequate maturation of Core as a trigger for induction of ER stress and UPR.
Malham Cove: splendour and enigma
Authors: Waltham Tony
Published: January 2017

A dry waterfall that recently came to life, a landform that is not karstic in the middle of a great karst terrain, underground drainage that is not as simple as it seems, and on‐going debate about how it was formed: Malham Cove is more than just a spectacular sight.