bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Rehabilitation
Authors: Fehlings Michael G. , Tetreault Lindsay A. , Aarabi Bizhan , Anderson Paul , Arnold Paul M. , Brodke Darrel S. , Chiba Kazuhiro , Dettori Joseph R. , Furlan Julio C. , Harrop James S. , Hawryluk Gregory , Holly Langston T. , Howley Susan , Jeji Tara , Kalsi-Ryan Sukhvinder , Kotter Mark , Kurpad Shekar , Kwon Brian K. , Marino Ralph J. , Martin Allan R. , Massicotte Eric , Merli Geno , Middleton James W. , Nakashima Hiroaki , Nagoshi Narihito , Palmieri Katherine , Singh Anoushka , Skelly Andrea C. , Tsai Eve C. , Vaccaro Alexander , Wilson Jefferson R. , Yee Albert , Burns Anthony S.
Published: September 2017

Introduction:

The objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI).

Methods:

A systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.

Results:

Based on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight–supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence).

Conclusions:

These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions.
A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Anticoagulant Thromboprophylaxis
Authors: Fehlings Michael G. , Tetreault Lindsay A. , Aarabi Bizhan , Anderson Paul , Arnold Paul M. , Brodke Darrel S. , Burns Anthony S. , Chiba Kazuhiro , Dettori Joseph R. , Furlan Julio C. , Hawryluk Gregory , Holly Langston T. , Howley Susan , Jeji Tara , Kalsi-Ryan Sukhvinder , Kotter Mark , Kurpad Shekar , Kwon Brian K. , Marino Ralph J. , Martin Allan R. , Massicotte Eric , Merli Geno , Middleton James W. , Nakashima Hiroaki , Nagoshi Narihito , Palmieri Katherine , Singh Anoushka , Skelly Andrea C. , Tsai Eve C. , Vaccaro Alexander , Wilson Jefferson R. , Yee Albert , Harrop James S.
Published: September 2017

Introduction:

The objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI).

Methods:

A systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.”

Results:

Based on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) “We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the risk of thromboembolic events in the acute period after SCI;” (2) “We suggest that anticoagulant thromboprophylaxis, consisting of either subcutaneous low-molecular-weight heparin or fixed, low-dose unfractionated heparin (UFH) be offered to reduce the risk of thromboembolic events in the acute period after SCI. Given the potential for increased bleeding events with the use of adjusted-dose UFH, we suggest against this option;” (3) “We suggest commencing anticoagulant thromboprophylaxis within the first 72 hours after injury, if possible, in order to minimize the risk of venous thromboembolic complications during the period of acute hospitalization.”

Conclusions:

These guidelines should be implemented into clinical practice in patients with SCI to promote standardization of care, decrease heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.
Type and Timing of Rehabilitation Following Acute and Subacute Spinal Cord Injury: A Systematic Review
Authors: Burns Anthony S. , Marino Ralph J. , Kalsi-Ryan Sukhvinder , Middleton James W. , Tetreault Lindsay A. , Dettori Joseph R. , Mihalovich Kathryn E. , Fehlings Michael G.
Published: September 2017

Objectives:

The objective of this study was to conduct a systematic review of the literature to address the following clinical questions: In adult patients with acute and subacute complete or incomplete traumatic SCI, (1) does the time interval between injury and commencing rehabilitation affect outcome?; (2) what is the comparative effectiveness of different rehabilitation strategies, including different intensities and durations of treatment?; (3) are there patient or injury characteristics that affect the efficacy of rehabilitation?; and (4) what is the cost-effectiveness of various rehabilitation strategies?

Methods:

A systematic search was conducted for literature published through March 31, 2015 that evaluated rehabilitation strategies in adults with acute or subacute traumatic SCI at any level. Studies were critically appraised individually and the overall strength of evidence was evaluated using methods proposed by the GRADE (Grades of Recommendation Assessment, Development and Evaluation) working group.

Results:

The search strategy yielded 384 articles, 19 of which met our inclusion criteria. Based on our results, there was no difference between body weight–supported treadmill training and conventional rehabilitation with respect to improvements in Functional Independence Measure (FIM) Locomotor score, Lower Extremity Motor Scores, the distance walked in 6 minutes or gait velocity over 15.2 m. Functional electrical therapy resulted in slightly better FIM Motor, FIM Self-Care, and Spinal Cord Independence Measure Self-Care subscores compared with conventional occupational therapy. Comparisons using the Toronto Rehabilitation Institute Hand Function Test demonstrated no differences between groups in 7 of 9 domains. There were no clinically important differences in Maximal Lean Test, Maximal Sidewards Reach Test, T-shirt Test, or the Canadian Occupational Performance Measure between unsupported sitting training and standard in-patient rehabilitation.

Conclusion:

The current evidence base for rehabilitation following acute and subacute spinal cord injury is limited. Methodological challenges have contributed to this and further research is still needed.
A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate
Authors: Fehlings Michael G. , Wilson Jefferson R. , Tetreault Lindsay A. , Aarabi Bizhan , Anderson Paul , Arnold Paul M. , Brodke Darrel S. , Burns Anthony S. , Chiba Kazuhiro , Dettori Joseph R. , Furlan Julio C. , Hawryluk Gregory , Holly Langston T. , Howley Susan , Jeji Tara , Kalsi-Ryan Sukhvinder , Kotter Mark , Kurpad Shekar , Kwon Brian K. , Marino Ralph J. , Martin Allan R. , Massicotte Eric , Merli Geno , Middleton James W. , Nakashima Hiroaki , Nagoshi Narihito , Palmieri Katherine , Skelly Andrea C. , Singh Anoushka , Tsai Eve C. , Vaccaro Alexander , Yee Albert , Harrop James S.
Published: September 2017

Introduction:

The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI).

Methods:

A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.”

Results:

The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) “We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI”; (2) “We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option”; and (3) “We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI.”

Conclusions:

These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients.
A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role of Baseline Magnetic Resonance Imaging in Clinical Decision Making and Outcome Prediction
Authors: Fehlings Michael G. , Martin Allan R. , Tetreault Lindsay A. , Aarabi Bizhan , Anderson Paul , Arnold Paul M. , Brodke Darrel , Burns Anthony S. , Chiba Kazuhiro , Dettori Joseph R. , Furlan Julio C. , Hawryluk Gregory , Holly Langston T. , Howley Susan , Jeji Tara , Kalsi-Ryan Sukhvinder , Kotter Mark , Kurpad Shekar , Kwon Brian K. , Marino Ralph J. , Massicotte Eric , Merli Geno , Middleton James W. , Nakashima Hiroaki , Nagoshi Narihito , Palmieri Katherine , Singh Anoushka , Skelly Andrea C. , Tsai Eve C. , Vaccaro Alexander , Wilson Jefferson R. , Yee Albert , Harrop James S.
Published: September 2017

Introduction:

The objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI).

Methods:

A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.”

Results:

Based on the limited available evidence and the clinical expertise of the GDG, our recommendations were: (1) “We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention, when feasible, to facilitate improved clinical decision-making” (quality of evidence, very low) and (2) “We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome” (quality of evidence, low).

Conclusions:

These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI.
A Clinical Practice Guideline for the Management of Acute Spinal Cord Injury: Introduction, Rationale, and Scope
Authors: Fehlings Michael G. , Tetreault Lindsay A. , Wilson Jefferson R. , Kwon Brian K. , Burns Anthony S. , Martin Allan R. , Hawryluk Gregory , Harrop James S.
Published: September 2017

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient’s physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of magnetic resonance imaging, and the type and timing of rehabilitation. This lack of consensus has prevented the standardization of care across treatment centers and among the various disciplines that encounter patients with SCI. The objective of this guideline is to form evidence-based recommendations for these areas of controversy and outline how to best manage patients with SCI. The ultimate goal of these guidelines is to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care and encouraging clinicians to make evidence-informed decisions.
Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review
Authors: Fehlings Michael G. , Wilson Jefferson R. , Harrop James S. , Kwon Brian K. , Tetreault Lindsay A. , Arnold Paul M. , Singh Jeffrey M. , Hawryluk Gregory , Dettori Joseph R.
Published: September 2017

Study Design:

Systematic review and meta-analysis.

Objective:

The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI).

Methods:

A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated and evaluated using the Assessment of Multiple Systematic Reviews scoring system.

Results:

The search yielded 723 citations, 13 of which satisfied inclusion criteria. Among these, 6 were primary research articles and 7 were previous systematic reviews. Based on the included research articles, there was moderate evidence that the 24-hour NASCIS II (National Acute Spinal Cord Injury Studies) MPSS regimen has no impact on long-term neurological recovery when all postinjury time points are considered. However, there is also moderate evidence that subjects receiving the same MPSS regimen within 8 hours of injury achieve an additional 3.2 points (95% confidence interval = 0.10 to 6.33; P = .04) of motor recovery compared with patients receiving placebo or no treatment.

Conclusion:

Although safe to administer, a 24-hour NASCIS II MPSS regimen, when all postinjury time points are considered, has no impact on indices of long-term neurological recovery. When commenced within 8 hours of injury, however, a high-dose 24-hour regimen of MPSS confers a small positive benefit on long-term motor recovery and should be considered a treatment option for patients with SCI.
A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury and Central Cord Syndrome: Recommendations on the Timing (≤24 Hours Versus >24 Hours) of Decompressive Surgery
Authors: Fehlings Michael G. , Tetreault Lindsay A. , Wilson Jefferson R. , Aarabi Bizhan , Anderson Paul , Arnold Paul M. , Brodke Darrel S. , Burns Anthony S. , Chiba Kazuhiro , Dettori Joseph R. , Furlan Julio C. , Hawryluk Gregory , Holly Langston T. , Howley Susan , Jeji Tara , Kalsi-Ryan Sukhvinder , Kotter Mark , Kurpad Shekar , Marino Ralph J. , Martin Allan R. , Massicotte Eric , Merli Geno , Middleton James W. , Nakashima Hiroaki , Nagoshi Narihito , Palmieri Katherine , Singh Anoushka , Skelly Andrea C. , Tsai Eve C. , Vaccaro Alexander , Yee Albert , Harrop James S.
Published: September 2017

Objective:

To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome.

Methods:

A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as “we recommend,” whereas a weak recommendation is presented as “we suggest.”

Results:

Conclusions from the systematic review included (1) isolated studies reported statistically significant and clinically important improvements following early decompression at 6 months and following discharge from inpatient rehabilitation; (2) in one study on acute central cord syndrome without instability, a marginally significant improvement in total motor scores was reported at 6 and 12 months in patients managed with early versus late surgery; and (3) there were no significant differences in length of acute care/rehabilitation stay or in rates of complications between treatment groups. Our recommendations were: “We suggest that early surgery be considered as a treatment option in adult patients with traumatic central cord syndrome” and “We suggest that early surgery be offered as an option for adult acute SCI patients regardless of level.” Quality of evidence for both recommendations was considered low.

Conclusions:

These guidelines should be implemented into clinical practice to improve outcomes in patients with acute SCI and central cord syndrome by promoting standardization of care, decreasing the heterogeneity of management strategies, and encouraging clinicians to make evidence-informed decisions.
Operationalizing Relative Customer Value
Authors: Keiningham Timothy , Aksoy Lerzan , Cadet Fabienne
Published: September 2017

The construct of “value” has been central to explaining economic exchange since the time of Adam Smith. Despite its central importance, debate still exists as to what value entails. Absent a comprehensive understanding of value, researchers and managers have grappled with how to measure and manage value. Not surprisingly, absent a definition, no comprehensive, robust approach has emerged.

We argue that value first must be viewed as a dual construct, i.e. value to the customer and value to the firm, that must be balanced to be sustainable. Given that value to the customer is clearly assessed as relative to competitive alternatives, we also argue that any robust measurement of value must account for competitive alternatives.

We propose applying recent research on the use of relative metrics in linking to share of category spending as the foundation of assessing value to the customer (particularly since customers in most categories divide their spending across competing firms). This allows firms to assess the monetary value customers’ assign to their offerings, and to estimate changes in this value from different market actions. As value to the firm is ultimately about the net present value of customers’ economic contributions to the firm, this allows firms to balance value to the customer with value to the firm.
The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke
Authors: Makin Stephen DJ , Doubal Fergus N , Quinn Terence J , Bath Philip MW , Dennis Martin S , Wardlaw Joanna M
Published: September 2017

Background

Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints.

Methods

We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS ≤ 7) and assessed recurrent vascular events (stroke, transient ischaemic attack (TIA), ischemic heart disease (IHD)), modified Rankin Score (mRS) and cognitive testing with the Addenbrooke’s Cognitive Examination (ACE-R) one year post-stroke. For a potential secondary prevention randomised controlled trial (RCT), we estimated sample sizes using individual or combined outcomes, at power 80% (and 90%), alpha 5%, required to detect a relative 10% risk reduction.

Results

Amongst 264 patients (118 lacunar, 146 non-lacunar), at one year, 30/264 (11%) patients had a recurrent vascular event, 5 (2%) had died, 3 (1%) had clinically-diagnosed dementia, 53/264 (20%) had mRS ≥ 3 and 29/158 (19%) had ACE-R ≤ 82 (57 could not attend for cognitive testing). For a potential trial, at 80% power, using mRS ≥ 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R ≤ 82, dementia or mRS ≥ 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke.

Conclusions

Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies.
Contraception and fertility transition in AMHARA National Regional State of ETHIOPIA: an application of BONGAARTS’ model
Authors: Alazbih Nega Mihret , Tewabe Getachew Nibret , Demissie Tariku Dejene
Published: September 2017

Background

The overall decline of fertility in Amhara National Regional State between 2000 and 2011 was the highest in Ethiopia. The aim of the present study was to determine the most significant proximate determinant of fertility change during the last decade in the region using Bongaarts’ model.

Methods

The sources of data were the 2000, 2005, and 2011 Ethiopia Demographic and Health Surveys. The model indices were calculated for each survey. Decomposition of fertility change into components of proximal determinants was also carried out. An index value close to 1 is a negligible inhibiting effect while a large inhibiting effect when the value very closes to 0.

Results

The fertility-constraining effect of contraception increased from 0.93 in 2000 to 0.65 in 2011; however, it was lower than the effect of postpartum insusceptibility at all given times. The index of marriage remained unchanged in constraining fertility over the period (0.71 in 2000 and 0.70 in 2011) while the influence of postpartum insusceptibility slightly declined from 0.49 in 2000 to 0.54 in 2011 but was stronger than contraception and marriage. The contribution of contraception was most important in urban areas (0.46 in 2011 from 0.52 in 2005 and 0.64 in 2000); however, in rural areas, it became an important determinant over the period (0.95 in 2000 and 0.69 in 2011). The effect of postpartum insusceptibility in rural areas showed a decreasing trend (0.48 in 2000 and 0.53 in 2011). The index of marriage in rural areas was stable overtime (0.75 in 2000 and 0.73 in 2011) while in urban areas the effect declined from 0.42 in 2000 to 0.65 in 2011. Marriage was the most important proximate determinant of fertility among women with secondary and above education but the impact declined during the period (0.41 in 2000 and 0.61 in 2011). The importance of postpartum insusceptibility in limiting fertility among women with secondary and above education declined overtime (0.77 in 2000 and 0.87 in 2011) whereas the contribution of contraception became more important (0.44 in 2000 and 0.35 in 2011).

Conclusions

An increase in the level of contraceptive use and effectiveness overtime was the single most important contributing factor for the recent fertility decline in the region.
Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study
Authors: Reiss Kim A. , Yu Shun , Mamtani Ronac , Mehta Rajni , D’Addeo Kathryn , Wileyto E. Paul , Taddei Tamar H. , Kaplan David E.
Published: September 2017

Purpose

Sorafenib is currently the only Food and Drug Administration–approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs.

Patients and Methods

We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os).

Results

There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047).

Conclusion

The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.
Klf5 maintains the balance of primitive endoderm versus epiblast specification during mouse embryonic development by suppression of Fgf4
Authors: Azami Takuya , Waku Tsuyoshi , Matsumoto Ken , Jeon Hyojung , Muratani Masafumi , Kawashima Akihiro , Yanagisawa Jun , Manabe Ichiro , Nagai Ryozo , Kunath Tilo , Nakamura Tomonori , Kurimoto Kazuki , Saitou Mitinori , Takahashi Satoru , Ema Masatsugu
Published: September 2017

The inner cell mass of the mouse blastocyst gives rise to the pluripotent epiblast (EPI), which forms the embryo proper, and the primitive endoderm (PrE), which forms extra-embryonic yolk sac tissues. All inner cells coexpress lineage markers such as Nanog and Gata6 at embryonic day (E) 3.25, and the EPI and PrE precursor cells eventually segregate to exclusively express Nanog and Gata6, respectively. Fibroblast growth factor (FGF)–extracellular signal-regulated kinase (ERK) signalling is involved in segregation of the EPI and PrE lineages; however, the mechanism involved in Fgf4 regulation is poorly understood. Here, we identified Klf5 as an upstream repressor of Fgf4. Fgf4 was markedly upregulated in Klf5 knockout (KO) embryos at E3.0, and was downregulated in embryos overexpressing Klf5. Furthermore, Klf5 KO and overexpressing blastocysts showed skewed lineage specification phenotypes, similar to FGF4-treated preimplantation embryos and Fgf4 KO embryos, respectively. Inhibitors of the FGF receptor (Fgfr) and ERK pathways reversed the skewed lineage specification of Klf5 KO blastocysts. These data demonstrate that Klf5 suppresses Fgf4-Fgfr-ERK signalling, thus preventing precocious activation of the PrE specification programme.
Loss of OCRL increases ciliary PI(4,5)P2 in Lowe oculocerebrorenal syndrome
Authors: Prosseda Philipp P. , Luo Na , Wang Biao , Alvarado Jorge A. , Hu Yang , Sun Yang
Published: September 2017

Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood. Here, we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P. In particular, subcellular distribution of PI(4,5)P2 build-up was observed at the transition zone. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from Lowe syndrome mouse model as well as in Ocrl-null MEFs, which was reversed by reintroduction of OCRL. Similarly, expression of wild-type OCRL reversed the elevated PI(4,5)P2 in Lowe patient cells. Accumulation of sonic hedgehog protein in response to hedgehog agonist was decreased in MEFs derived from a Lowe syndrome mouse model. Together, our findings show for the first time an abnormality in ciliary phosphoinositides of both human and mouse cell models of Lowe syndrome.
Numerical simulation of heat exchange at cooling of high-temperature metal blank made of steel ChGSN2A
Authors: Макаров Сергей , Makarov Sergey , Дементьев Вячеслав , Dementiev V.
Published: September 2017

The results of the numerical simulation of heat exchange at the cooling metal blank made of steel 30ChGSN2A are shown. The velocities of blank cooling with the flow of gas-liquid medium are defined. Cooling intensity changes depending on the blank motion speed opposite the flow of cooling medium are analyzed.
Forming mandrel use for slot hole calibration in heat-treated parts
Authors: Берберов Сергей , Berberov Sergey , Лебедев Валерий , Lebedev Valeriy
Published: September 2017

A design of the hard-alloy complex tool ensuring calibration of slot holes in heat-treated parts with high accuracy, minor roughness of the surface and a strengthened surface layer is presented.
Negative Dependence, Scrambled Nets, and Variance Bounds
Authors: Lemieux Christiane
Published: September 2017

In this paper, we provide a framework to study the dependence structure of sampling schemes such as those produced by randomized quasi-Monte Carlo methods. The main goal of this new framework is to determine conditions under which the negative dependence structure of a sampling scheme enables the construction of estimators with reduced variance compared to Monte Carlo estimators. To do this, we establish a generalization of the well-known Hoeffding’s lemma—expressing the covariance of two random variables as an integral of the difference between their joint distribution function and the product of their marginal distribution functions—that is particularly well suited to study such sampling schemes. We also provide explicit formulas for the joint distribution of pairs of points randomly chosen from a scrambled (0, m, s)-net. In addition, we provide variance bounds establishing the superiority of dependent sampling schemes over Monte Carlo in a few different setups. In particular, we show that a scrambled (0, m, 2)-net yields an estimator with variance no larger than a Monte Carlo estimator for functions monotone in each variable.
An Equilibrium Analysis of a Multiclass Queue with Endogenous Abandonments in Heavy Traffic
Authors: Ata Baris , Peng Xiaoshan
Published: September 2017

This paper studies a multiclass queueing system with endogenous abandonments where congestion affects customers’ abandonment behavior, and vice versa. Our model captures this interaction by developing two closely related models: an abandonment model and a queueing model. In the abandonment model, customers take the virtual waiting time distribution as given. Class k customers receive a reward rk from service and incur a cost ck per period of waiting. Customers are forward looking and make wait or abandon decisions dynamically to maximize their expected discounted utilities. The queueing model takes the customers’ abandonment time distribution as an input and studies the resulting virtual waiting time distribution. Because the multiclass queueing system is not amenable to exact analysis, we resort to an approximate analysis in the conventional heavy traffic limit (under the hazard rate scaling). Leveraging the so-called state-space collapse property, we provide a characterization of the system performance. Combining the results for the two models, we show that there exists a unique equilibrium in which the customers’ abandonment time and the virtual waiting time for the various classes are consistent in the two models. Finally, we provide a computational scheme to calculate the equilibrium numerically and apply that using data from an Israeli bank call center.

The online appendix is available at https://doi.org/10.1287/opre.2017.1638 .
v3NLP Framework: Tools to Build Applications for Extracting Concepts from Clinical
Text
Authors: Divita Guy , Carter Marjorie , Tran Le-Thuy , Redd Doug , Zeng Qing T. , Duvall Scott , Samore Matthew H. , Gundlapalli Adi V.
Published: September 2017

Introduction: Substantial amounts of clinically significant information are
contained only within the narrative of the clinical notes in electronic medical records.
v3NLP Framework is a set of best of breed functionalities developed to transform this
information into structured data for use in quality improvement, research, population
health surveillance, and decision support.Background: MetaMap, cTAKES and similar well
known NLP tools do not have sufficient scalability out of the box. v3NLP Framework
evolved out of the necessity to scale these tools up and provide a framework to
customize and tune techniques to fit a variety of tasks, including document
classification, tuned concept extraction for specific conditions, patient
classification, and information retrieval.Innovation: Beyond scalability, several v3NLP
Framework developed projects have been efficacy tested and benchmarked. While v3NLP
Framework includes annotators, pipelines and applications, the functionalities enable
developers to create novel annotators, put annotators into pipelines and scaled
applications.Discussion: v3NLP Framework has been successfully utilized in many projects
including general concept extraction, risk factors for homelessness among veterans, and
identification of mentions of the presence of an indwelling urinary catheter. Projects
as diverse as predicting colonization with methicillin resistant Staphylococcus aureus
and extracting references to military sexual trauma are being built using v3NLP
Framework components.Conclusion: v3NLP Framework is a set of functionalities and
components that provide Java developers the ability to create novel annotators, place
annotators into pipelines, and applications to extract concepts from clinical text.
There are scale-up and scale-out functionalities to process large numbers of
records.
eGEMs: An Opportunity for Better Science
Authors: Wallace Paul
Published: September 2017

eGEMs faces two early challenges in its effort to effort to disseminate knowledge
and new ideas about the use of electronic clinical data for research: attracting readers
and producing better science. The health services grey literature and the microchip
industry are two areas of knowledge generation that provide important insight for how
eGEMs can achieve these goals. In order to achieve its goals, eGEMs should aim to
promote rapid sharing of ideas, engage sponsors and potential users of research findings
early in the process, develop metrics for success to guide research efforts, and recruit
diverse contributors. Success would allow for not just the generation of new research,
but also new science, which has the potential to significantly improve patient
outcomes.
Zwischen Green Growth und De-Growth
Authors: Beckenbach Frank , Wagner Bernd , Welsch Heinz
Published: September 2017

Der Zusammenhang von Wachstum und Nachhaltiger Entwicklung steht im Kern einerNachhaltigkeitsökonomik. Um eine Rückführung umweltbelastender Mengenströme zu erreichen, müssen zunächst die Wachstumstreiber für Konsumenten und Produzenten identifiziert werden.
Wirtschaftswissenschaftliche Ansätze zur Gestaltung von Wandlungsprozessen
Authors: Antes Ralf , Eisenack Klaus , Fichter Klaus
Published: September 2017

Nachhaltige Entwicklung kann nur durch einen gesellschaftlichen Wandel umgesetzt werden. Im Zentrum dieses Wandels steht eine grundlegende Transformation der aktuellen Wirtschaftsweise. Der folgende Beitrag zeigt auf, welche Forschungsthemen, sowohl für die gesamt- als auch die einzelwirtschaftliche Ebene, von fundamentaler Bedeutung sind.
Die Krise als Katalysator der Theoriebildung?
Authors: Sturn Richard
Published: September 2017

Die gegenwärtige Krise könnte auch zur Weiterentwicklung der Ökonomik dienen. Doch welche Leitideen lassen sich für die Entwicklung von Institutionen und Mechanismen formulieren? Überlegungen zur Institutionenökonomik in Zeiten krisenhafter Übergänge.
Bewertung von Unternehmen im Lebensmittelsektor
Authors: Schader Christian , Jawtusch Julia , Stolze Matthias
Published: September 2017

Die Welternährungsorganisation FAO hat nun erstmals eine umfassende Definition von Nachhaltigkeit für den Lebensmittelsektor  vorgelegt. Auf dieser Basis wurde mit SMART eine Methode entwickelt, anhand derer Unternehmen aus dem Lebensmittelbereich ihre Nachhaltigkeitsleistungen darstellen können.
Wie die Bundesregierung den Klimaschutz und sparsame Neuwagen ausbremst
Authors: Müller-Görnert Michael
Published: September 2017

Die Bundesregierung hat erneut die Verschärfung von Abgasnormen verzögert, obwohl diese von der EU bereits vereinbart wurden. Damit macht sich die Bundesregierung zum Handlanger der Autolobby.
Wissenstransfer in der sozioökonomischen Wasserforschung
Authors: Maschke Philip , Petschow Ulrich , Hirschfeld Jesko
Published: September 2017

Nicht nur vor dem Hintergrund des Klimawandels wird die Ressource Wasser immer wichtiger. Um den Herausforderungen zu begegnen, ist eine sozioökonomische Wasserforschung notwendig. Doch wie können die dabei generierten sozioökonomischen Erkenntnisse in die Praxis einfließen?
Nationale Strategien für nachhaltige Biomassenutzung in Afrika
Authors: Janssen Rainer , Rutz Dominik , Khawaja Cosette
Published: September 2017

Nachhaltige Biomassenutzung ist auch in Afrika auf dem Vormarsch. Nationale Strategien sowie rechtliche und ordnungspolitische Rahmenbedingungen spielen dabei eine wichtige Rolle. Welche Bedeutung hat die Anpassung solcher Strategien auf die jeweiligen nationalen, regionalen und lokalen Begebenheiten?
Equivalent Circuit Parametrization Utilizing FE Model Order Reduction and its Application to Piezoelectric Generators and Actuators
Authors: Wurpts Wiebold , Twiefel Jens , Brouet Francois
Published: September 2017

Equivalent circuits are often the first choice for the modeling of piezoelectric systems, as they allow for the consideration of the complete electro-mechanical system with one or even more modes. The parameters of the equivalent circuit model are identified by a measured or simulated frequency response. In this contribution a method for a direct modal condensation of the equivalent parameters for arbitrary FE structures and loads is described and discussed. First the proposed method is demonstrated for a continuous piezoelectric rod and then applied to discrete finite element models. The derived equivalent circuit has an identical appearance to the classical solution, but additionally allows arbitrarily load conditions. Furthermore, the structure of the derived equivalent circuit depends on whether short- or open-circuited modes are used for the modal expansion. The influence of truncated modes is discussed utilizing residual terms, leading to a better understanding of the circuit parameters. Additionally the model based approaches in the third part an experimental parameter identification procedure for many modes is presented as well. The influence of the load and the quality of the model order reduction are discussed for piezoelectric rods. The methods are demonstrated for a base excited energy harvesting system an ultrasonic grubber.
Sulfates of Sorghum vinegar residue waste as potential catalysts
Authors: Qiao Yuanbiao , Qin Wenhao , Li Qingshan
Published: September 2017

A sealed wet curing design on sulfatingSorghumvinegar residue waste is drilled with sulfo/sulfoalkyl chemicals. Sulfation degrees in the case of reactions with sulfuric acid, sodium sulfite, sulfamic acid, benzenesulfonic acid,p-toluenesulfonic acid and sodium laurilsulfate range from 14.7 to 36.9 mg sulfo per gram waste. The C–O–S formation gives rise to accessional noncrystallinity and mesoporosity of morphology, a character for potential alternatives in catalysis. Waste sulfates are employed as candidates in catalyzing the condensation of α-glycolic acid and urea substitutes for yielding imidazolidine-2,4-dione derivatives. Catalytic and specific activities in terms of derivative productions are 2.6–34.3 (×103U) and 0.8–5.4 U/mg sulfo, together with the maximal yields of 49.4%–97.6%. Chemical linkage of sulfo/sulfoalkyl groups manifests synergism with intrinsic acidity of waste with respect to catalysis. A rational design of green chemistry is guaranteed by no excess of chemicals and easy recyclability of catalysts.
Influence of Thermal Ageing on Microstructure and Tensile Properties of P92 Steel
Authors: Sakthivel T. , Selvi S. Panneer , Parameswaran P. , Laha K.
Published: September 2017

Microstructure and tensile properties of P92 steel in the normalized and tempered, and thermal aged at 923 K for 5000 h and 10,000 h conditions have been investigated. Laves phase precipitate was observed in the thermal-aged steels. The size of Laves phase precipitate increased with increase in thermal exposure. This was also confirmed from the observation that the area fraction of Laves phase precipitate was higher in the 5000 h aged condition which decreased with further increase in thermal exposure. On the other hand, the size and area fraction of M23C6 precipitate were found increased in the 5000 h aged steel, further continued to enhanced precipitation of fine M23C6 in the 10,000 h aged steel. This resulted in significant increase in area fraction and comparable size with the steel aged for 5000 h. Hardness of the steel was decreased with increase in the duration of ageing. Thermal-aged steels exhibited lower yield stress, ultimate tensile strength and relatively higher ductility in comparison with steel in the normalized and tempered condition. The increase in lath width and recovery of dislocation structure under thermal-aged condition resulted in lower tensile strength and hardness. An extensive Laves phase formation and coarsening by loss of tungsten in the matrix led to decrease in the tensile strength predominantly in the 5000 h aged steel. The tensile strength of 10,000 h aged steel was comparable with that of 5000 h aged steel due to enhanced precipitation of fine M23C6 in the steel due to enhanced mobility of carbon in the absence of tungsten in the matrix.
The organization of flint processing in the Bronze Age and Early Iron Age: the example of the workshops at Nieborowa in central-eastern Poland
Authors: Boroń Tomasz
Published: September 2017

Die Fundstelle Nieborowa – im zentral-östlichen Polen an der Grenze zu der Łęczyńsko-Włodawskie Seenplatte und den Chełm Hügeln gelegen – wurde von Halina Mackiewicz (Institut für die Geschichte der Materiellen Kultur [seit 1992 Institut für Archäologie und Ethnologie der Polnischen Akademie der Wissenschaften]) in den Jahren 1964–1977 untersucht. Auf einem Gebiet von über 3500 m

Der Lagerplatz bestand aus vier Werkstätten – zwei planigraphisch abgegrenzte (A, B) und zwei auf Basis der zusammengefügten Elemente rekonstruierte Werkstätten (C, D). Alle Werkstätten wiesen einen Durchmesser von etwa 1 m auf, die Entfernung zwischen ihnen betrug zwischen 1 und 3 m. Übereinstimmende Beobachtungen wie die Verwendung gleicher Feuersteinmaterialien und die Anwendung identischer Techniken zur Kernbearbeitung erlauben die Annahme gleichzeitig arbeitender Werkstätten. Die Distribution der Artefakte, die Struktur der Zusammenlegungen, die Homogenität des Feuersteininventars und die Separierung der Werkplätze zur Kernbearbeitung innerhalb jeder Werkstatt sprechen für eine singulär erfolgte Ansiedlung.

Im Fall der besprochenen Werkstätten konnte erkannt werden, dass die Organisation der Bearbeitung des lokalen Feuersteinrohstoffes nach einem wiederkehrenden Schema erfolgte.
Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior
Authors: Pérez-Domínguez Martha , Tovar-y-Romo Luis B. , Zepeda Angélica
Published: September 2017

The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.