bluuebunny/crossref_metadata_2025 huggingface dataset:
The Fiscal Savings Behavior of Pennsylvania School Districts Through the Great Recession
Authors: Arapis Theodore , Reitano Vincent , Bruck Earl
Published: April 2017

While researchers have examined fiscal stabilization for state and local governments, less attention has been dedicated to special purpose governments, such as school districts. This paper fills the gap by examining the general unassigned fund balance of Pennsylvania school districts before and after the Great Recession using a Two‐Step Generalized Method of Moments estimator. Although Pennsylvania imposes limitations on the unassigned fund balance, half of school districts are non‐compliant, choosing instead to accumulate savings above the limits to improve their budget flexibility. Since the Great Recession, however, state revenue constraints have challenged savings accumulation. Additionally, while districts use savings for covering expenditures, less unassigned fund balance was drained during downturn years due to cutback management. Collectively, these findings signal a “new normal” for Pennsylvania districts.
The Value of Weather Information for E‐Commerce Operations
Authors: Steinker Sebastian , Hoberg Kai , Thonemann Ulrich W.
Published: April 2017

To be efficient, logistics operations in e‐commerce require warehousing and transportation resources to be aligned with sales. Customer orders must be fulfilled with short lead times to ensure high customer satisfaction, and the costly under‐utilization of workers must be avoided. To approach this ideal, forecasting order quantities with high accuracy is essential. Many drivers of online sales, including seasonality, special promotions and public holidays, are well known, and they have been frequently incorporated into forecasting approaches. However, the impact of weather on e‐commerce operations has not been rigorously analyzed. In this study, we integrate weather data into the sales forecasting of the largest European online fashion retailer. We find that sunshine, temperature, and rain have a significant impact on daily sales, particularly in the summer, on weekends, and on days with extreme weather. Using weather forecasts, we have significantly improved sales forecast accuracy. We find that including weather data in the sales forecast model can lead to fewer sales forecast errors, reducing them by, on average, 8.6% to 12.2% and up to 50.6% on summer weekends. In turn, the improvement in sales forecast accuracy has a measurable impact on logistics and warehousing operations. We quantify the value of incorporating weather forecasts in the planning process for the order fulfillment center workforce and show how their incorporation can be leveraged to reduce costs and increase performance. With a perfect information planning scenario, excess costs can be reduced by 11.6% compared with the cost reduction attainable with a baseline model that ignores weather information in workforce planning.
Lower limb muscle function and exercise performance in lung cancer
Authors: Maddocks Matthew , Granger Catherine
Published: April 2017

See DOI: 10.1111/resp.13041
Workplace culture in psychiatric nursing described by nurses
Authors: Kurjenluoma K. , Rantanen A. , McCormack B. , Slater P. , Hahtela N. , Suominen T.
Published: April 2017

Aim

This study looks to describe the workplace culture from the viewpoints of stress, job satisfaction and practice environment.

Methods

Data were collected from nurses (n = 109) using a web‐based survey, The Person‐Centred Nursing Index, from two purposefully selected hospital districts in Finland. Data were statistically analysed.

Results

Nurses described their workplace culture in slightly positive terms. Nurses only occasionally experienced stress (mean = 2.56, SD = 0.55) and were fairly satisfied with their job (mean = 4.75, SD = 0.66) and their practice environment (mean = 4.42, SD = 0.81). Demographic variables such as the nurses’ age, length of time in nursing, time at their present hospital, working shifts and their use of patient restriction were more frequently associated with their perceived workplace culture.

Conclusion

Older nurses and those with a longer work history in the nursing profession tended to be more satisfied with their workplace culture in psychiatric nursing. Young and/or newly graduated nurses felt more negatively on their workplace culture; this issue should be recognised and addressed with appropriate support and mentoring. Nurses who used restrictive measures were more often less satisfied with their workplace culture. Continuous efforts are needed to reduce the use of coercive measures, which challenge also the managers to support nursing practice to be more person‐centred.
Flashbulb memories of the Paris attacks
Authors: Gandolphe Marie‐Charlotte , El Haj Mohamad
Published: April 2017

Flashbulb memories are vivid autobiographical memories of the circumstances where an individual first learns about emotionally significant public events. Our paper assesses whether these memories were triggered by the attacks of Friday 13 November 2015 in Paris. Two hundred and ninety‐one participants answered a web‐based questionnaire that assessed their memory of the circumstances in which they first learned of the attacks. The questionnaire also assessed vividness, rehearsal, emotion, surprise and novelty. The results showed substantial and vivid recall of the context in which the participants first learned of the event. This recall was associated with fair rehearsal, negative emotional valence, surprise, and novelty. Regression analysis showed that the flashbulb recall was predicted by negative emotion. Negative emotion seems to play a key role in the formation of flashbulb memories, at least those associated with the Paris attacks.
Regulation of the turnover of ACC synthases by phytohormones and heterodimerization in Arabidopsis
Authors: Lee Han Yong , Chen Yi‐Chun , Kieber Joseph J. , Yoon Gyeong Mee
Published: April 2017

Ethylene influences many aspects of plant growth and development. The biosynthesis of ethylene is highly regulated by a variety of internal and external cues. A key target of this regulation is 1‐aminocyclopropane‐1‐carboxylic acid (ACC) synthases (ACS), generally the rate‐limiting step in ethylene biosynthesis, which is regulated both transcriptionally and post‐transcriptionally. Prior studies have demonstrated that cytokinin and brassinosteroid (BR) act as regulatory inputs to elevate ethylene biosynthesis by increasing the stability of ACS proteins. Here, we demonstrate that several additional phytohormones also regulate ACS protein turnover. Abscisic acid, auxin, gibberellic acid, methyl jasmonic acid, and salicylic acid differentially regulate the stability of ACS proteins, with distinct effects on various isoforms. In addition, we demonstrate that heterodimerization influences the stability of ACS proteins. Heterodimerization between ACS isoforms from distinct subclades results in increased stability of the shorter‐lived partner. Together, our study provides a comprehensive understanding of the roles of various phytohormones on ACS protein stability, which brings new insights into crosstalk between ethylene and other phytohormones, and a novel regulatory mechanism that controls ACS protein stability through a heterodimerization of ACS isoforms.
Antithrombotic therapy and platelet transfusions in hematologic malignancy patients presenting chemotherapy‐induced thrombocytopenia: a French survey
Authors: Chalayer Emilie , Cavalieri Doriane , Martignoles Jean Alain , Genthon Alexis , Tavernier Emmanuelle , Tardy Bernard
Published: April 2017

BACKGROUND

Patients with hematologic malignancies are at high risk for both thrombosis and bleeding. During the prolonged periods of thrombocytopenia experienced by patients who are receiving intensive chemotherapy, clinicians often hesitate to prescribe any protection against thrombosis. In case of anticoagulant prescription, it is the prescribers' responsibility to weigh risks and benefits for each patient. Current guidelines exist but do not take into account types of thrombosis, patients' comorbidities, or previous bleeding events.

STUDY DESIGN AND METHODS

We proposed to gain insight into hematologists' beliefs about antithrombotic prescription in hematologic malignancy patients, to design future clinical trials. Therefore, we conducted a survey in France to evaluate the practices among a panel of hematologists.

RESULTS

We found that more than 92% of the respondents prescribed therapeutic anticoagulation in case of pulmonary embolism or deep venous thrombosis. In the case of therapeutic anticoagulation, only 64% of the physicians reconsidered treatment under a platelet threshold of 50 × 109/L. None of the respondents decided to renounce treatment, nor to discontinue it because of thrombocytopenia, except in distal venous thrombosis or superficial vein thrombosis. One‐fifth of clinicians proposed the insertion of a vena cava filter.

CONCLUSION

As observed in the United States and Canada, we noticed discrepancies between recommendations and current practices in France. This highlights the urgent need to conduct studies to evaluate both efficacy and safety of antithrombotics in patients with hematologic cancer and thrombocytopenia.
Concentrated lyophilized plasma used for reconstitution of whole blood leads to higher coagulation factor activity but unchanged thrombin potential compared with fresh‐frozen plasma
Authors: Iapichino Giacomo E. , Ponschab Martin , Cadamuro Janne , Süssner Susanne , Gabriel Christian , Dieplinger Benjamin , Egger Margot , Schlimp Christoph J. , Bahrami Soheyl , Schöchl Herbert
Published: April 2017

BACKGROUND

During massive hemorrhage, it is recommended to transfuse red blood cells, platelet concentrate, and fresh‐frozen plasma in a ratio close to 1:1:1. To avoid the thawing process of fresh frozen plasma, lyophilized plasma (LP) is increasingly used. Evidence is limited on the activity of coagulation factors in reconstituted blood using LP and concentrated LP versions.

STUDY DESIGN AND METHODS

Whole blood from ten healthy volunteers was separated into red blood cell, fresh frozen plasma, and platelet concentrate units. Aliquots of red blood cells and plasma concentrate were mixed with either fresh frozen plasma (200 mL) or LP at reconstitution ratios of 2:1:1, 1:1:1, and 1:1:2. LP was used either at the recommended standard volume of 200 mL (LP200) or was more concentrated at volumes of 100 and 50 mL (LP100 and LP50, respectively). The hemostatic capacity of each reconstituted whole blood sample was tested with blood cell counts, standard coagulation tests, factor activity, thrombin generation, and viscoelastic assays.

RESULTS

Hematocrit, platelet counts, and fibrinogen levels of the three ratios were similar between FFP200 and LP200 units but were lower compared with the corresponding ratios in LP100 and LP50 units. The activity of procoagulant and anticoagulant factors increased linearly with the increasing plasmatic fraction and, at 1:1:2 ratio, was significantly higher in LP50 units compared with FFP200 and LP200 units. Thrombin generation was similar throughout the four plasma groups at any ratio.

CONCLUSIONS

Decreasing the dilution volume of LP facilitates reaching higher hematocrit and coagulation protein levels without a relevant increase in thrombin generation. This is due to preserved balance between procoagulant and anticoagulant factors in the concentrated LP preparations.
Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors
Authors: Sumner Scarlett M. , Naskou Maria C. , Thoresen Merrilee , Copland Ian , Peroni John F.
Published: April 2017

BACKGROUND

Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses.

STUDY DESIGN AND METHODS

Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours after the procedure. To produce platelet lysate, the platelet concentrate underwent two freeze‐thaw cycles followed by centrifugation and filtration processing. The platelet lysate was then analyzed for cellular debris, fibrinogen, and growth factors.

RESULTS

The collected platelet concentration contained a mean platelet yield of 390 × 103/μL. Donor platelet count decreased from a mean of 193 × 103/μL to 138 × 103/μL after plateletpheresis, but no individual was at risk for hemorrhage. Pooled platelet lysate had minimal cellular residue and contained growth factor concentrations at 6.1 ng/mL for transforming growth factor‐β1, at 3.5 ng/mL for platelet‐derived growth factor‐BB, and at 13.8 ng/mL for vascular endothelial growth factor‐A.

CONCLUSION

Plateletpheresis using commercially available apheresis equipment is a feasible option for collecting platelet concentrate from equine donors. The lysate generated from the apheresis product contains growth factors and has potential to be used as a fetal bovine serum substitute for cell culture.
Habit, prisoner's dilemma and Americans’ welfare cost of working much more than Europeans
Authors: Schiff Maurice
Published: April 2017

Europeans work much less than Americans. Some studies claim this is due to Europe's high taxes and that Europeans would gain by adopting US tax rates and work time. I argue that Americans would gain by reducing work time to Europe's level. Due to historical experience, Europe is able to internalise work‐time‐related negative externalities by enacting restrictive work‐time policies, while the United States is not, resulting in a prisoner's dilemma equilibrium and “overworking trap.” A simple model and work‐time data are used to derive theUSwelfare gain from reducing work time to Europe's level. Findings are as follows: (i) parameter values are consistent with experimental results on own vs. other people's income value; (ii) the welfare gain's present value is between 80 and 120% of annual welfare; and (iii) a European policy that reduces work time excessively remains beneficial if the reduction is less than twice the optimal one.
Therapeutic effectiveness of calcineurin inhibitors in canine vesicular cutaneous lupus erythematosus
Authors: Banovic Frane , Robson David , Linek Monika , Olivry Thierry
Published: April 2017

Background

Oral and topical calcineurin inhibitors (CIs) have been reported to lead to complete lesion remission in several dogs with vesicular cutaneous lupus erythematosus (VCLE).

Objectives

To report retrospectively on the effectiveness and adverse effects of systemic (ciclosporin) and/or topical (tacrolimus/pimecrolimus) CIs in 11 dogs with VCLE.

Methods

Inclusion criteria were: (i) presence of characteristic annular, polycyclic or serpiginous ulcerations distributed over the groin, axillae and/or ventral abdomen; (ii) a histopathological diagnosis of VCLE (i.e. a lymphocyte‐rich interface dermatitis with vesiculation); (iii) treatment that included CIs for at least eight weeks; and (iv) follow‐up until death/euthanasia or for a minimum of 12 months post‐diagnosis.

Results

Initial therapy included the avoidance of excessive sun exposure, oral glucocorticoids [six of 11 dogs (55%); progressively tapered over a month] and once daily ciclosporin [11 dogs (100%); median 5.8 mg/kg]. A complete remission (CR) of signs occurred between days 35 and 70 after starting CIs in eight dogs (73%); increasing ciclosporin dosage and adding topical tacrolimus induced a CR in two additional dogs (18%). Relapses were common when doses were tapered or discontinued. With the exception of three dogs that were euthanized, clinical signs were maintained in CR with oral ciclosporin (eight of eight dogs treated, 100%) or topical tacrolimus/pimecrolimus (four of eight dogs; 50%) with a median follow‐up of 2.9 years.

Conclusions and clinical importance

These observations support CIs as the preferable therapeutic alternatives to long‐term immunosuppression with oral glucocorticoids in dogs with VCLE.
Documenting decline in U.S. economic mobility
Authors: Katz Lawrence F. , Krueger Alan B.
Published: April 2017

Median incomes stagnate as inequality increases
Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections
Authors: Wang Wenshi , Yin Yuebang , Xu Lei , Su Junhong , Huang Fen , Wang Yijin , Boor Patrick P. C. , Chen Kan , Wang Wenhui , Cao Wanlu , Zhou Xinying , Liu Pengyu , van der Laan Luc J. W. , Kwekkeboom Jaap , Peppelenbosch Maikel P. , Pan Qiuwei
Published: April 2017

A tripartite transcription factor complex mediates an interferon-independent antiviral response.
Papers of note in
Nature
544
(7650)
Authors: VanHook Annalisa M.
Published: April 2017

This week’s articles show that vesicle fusion proteins are involved in long-term potentiation and highlight the structural properties that contribute to functional differences between angiotensin II receptors.
Active life, active antitumor defense
Authors: Ferrarelli Leslie K.
Published: April 2017

An active lifestyle in mice stimulates adrenergic signaling in the nervous system that enhances the function of antitumor natural killer cells.
Papers of note in
Science Translational Medicine
9
(386)
Authors: Ferrarelli Leslie K.
Published: April 2017

This week’s articles describe a new hydrogel that promotes chronic wound healing and a way to limit intestinal tissue damage from radiation, chemo, or hematopoietic cell transplant therapies.
Blocking a signal to host cell histones
Authors: Mushegian Alexandra A.
Published: April 2017

A plant pathogen suppresses the host immune response by preventing histone acetylation.
In Vitro
Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae
Authors: Huang Dennis , Yu Brenda , Diep John K. , Sharma Rajnikant , Dudley Michael , Monteiro Jussimara , Kaye Keith S. , Pogue Jason M. , Abboud Cely Saad , Rao Gauri G.
Published: April 2017

The multidrug resistance profiles of
Klebsiella pneumoniae
carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the
in vitro
activity of polymyxin B and minocycline combination therapy against six KPC-2-producing
K. pneumoniae
isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing
K. pneumoniae
is dependent on polymyxin B susceptibility. Further
in vitro
and animal studies must be performed to fully evaluate the efficacy of this drug combination.
Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both
bla
KPC
and
bla
CTX-M
Integrated in the Chromosome
Authors: Huang Weihua , Wang Guiqing , Sebra Robert , Zhuge Jian , Yin Changhong , Aguero-Rosenfeld Maria E. , Schuetz Audrey N. , Dimitrova Nevenka , Fallon John T.
Published: April 2017

The extended-spectrum-β-lactamase (ESBL)- and
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Enterobacteriaceae
represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant
K. pneumoniae
, we identified three clinical isolates, CN1, CR14, and NY9, carrying both
bla
CTX-M
and
bla
KPC
genes. The complete genomes of these three
K. pneumoniae
isolates were
de novo
assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9,
bla
CTX-M
and
bla
KPC
were carried on two different plasmids. In contrast, CN1 had one copy of
bla
KPC-2
and three copies of
bla
CTX-M-15
integrated in the chromosome, for which the
bla
CTX-M-15
genes were linked to an insertion sequence, IS
Ecp1
, whereas the
bla
KPC-2
gene was in the context of a Tn
4401a
transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn
4401a-bla
KPC-2
-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-
cas
array with four spacers targeting a variety of
K. pneumoniae
plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-
cas
in
K. pneumoniae
strains and suggested that the evolving CRISPR-
cas
, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of
bla
CTX-M
and
bla
KPC
from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant
K. pneumoniae
. Additionally, the implications from this study also raise concerns for the application of a CRISPR-
cas
strategy against antimicrobial resistance.
Demonstrating the Protective Efficacy of the Novel Fluoroquinolone Finafloxacin against an Inhalational Exposure to Burkholderia pseudomallei
Authors: Barnes Kay B. , Hamblin Karleigh A. , Richards Mark I. , Laws Thomas R. , Vente Andreas , Atkins Helen S. , Harding Sarah V.
Published: April 2017

Burkholderia pseudomallei
is the causative agent of melioidosis, a serious disease endemic in Southeast Asia and Northern Australia. Antibiotic treatment is lengthy and relapse often occurs. Finafloxacin is a novel fluoroquinolone with increased antibacterial activity in acidic conditions in contrast to other fluoroquinolones which demonstrate reduced activity at a lower pH. Therefore, finafloxacin may have improved efficacy against
B. pseudomallei
, which can survive within host cells where the local pH is acidic.
In vitro
analysis was performed using MICs, minimal bactericidal concentrations (MBCs), time-kill assays, persister cell assays, and macrophage assays. Finafloxacin showed increased bactericidal activity at pH 5 in comparison to pH 7 and ciprofloxacin at pH 5.
In vivo
studies in BALB/c mice included pharmacokinetic studies to inform an appropriate dosing regimen. Finafloxacin efficacy was evaluated in an inhalational murine model of melioidosis where antibiotic treatment was initiated at 6 or 24 h postchallenge and continued for 14 days, and mice were observed for 63 days. The survival of infected mice following 14 days of treatment was 80%, 60% or 0% for treatments initiated at 6 h and 60%, 30% or 0% for treatments initiated at 24 h for finafloxacin, co-trimoxazole, or ciprofloxacin, respectively. In summary, finafloxacin has increased bactericidal activity for
B. pseudomallei
under acidic conditions
in vitro
and improves survival in a murine model of melioidosis compared with those for ciprofloxacin. Furthermore, finafloxacin improves bacteriological clearance compared with that of co-trimoxazole, suggesting it may offer an effective postexposure prophylaxis against
B. pseudomallei
.
Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but Low Mortality in 22 Cases of Candidemia
Authors: Marcos-Zambrano Laura Judith , Puig-Asensio Mireia , Pérez-García Felipe , Escribano Pilar , Sánchez-Carrillo Carlos , Zaragoza Oscar , Padilla Belén , Cuenca-Estrella Manuel , Almirante Benito , Martín-Gómez M. Teresa , Muñoz Patricia , Bouza Emilio , Guinea Jesús
Published: April 2017

The objectives of our study were to describe the characteristics of patients with
Candida guilliermondii
candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with
C. albicans
candidemia. We described the risk factors and outcomes of 22 patients with candidemia caused by the
C. guilliermondii
complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin, and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the
Galleria mellonella
model. Biofilm formation was compared with that observed for
C. albicans
. The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by the
C. guilliermondii
complex than in patients infected by
C. albicans
, and 30-day mortality was lower in
C. guilliermondii
patients (13.6% versus 33.9%, respectively;
P
= 0.049). Isolates were identified as
C. guilliermondii
sensu stricto
(
n
= 17) and
Candida fermentati
(
n
= 5). The isolates produced biofilms with low metabolic activity and moderate biomass. The
G. mellonella
model showed that
C. guilliermondii
was less virulent than
C. albicans
(mean of 6 days versus 1 day of survival, respectively;
P
< 0.001). Patients with candidemia caused by the
C. guilliermondii
complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with a favorable outcome.
Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis
Authors: Olliaro Piero L. , Merle Corinne , Mthiyane Thuli , Bah Boubacar , Kassa Ferdinand , Amukoye Evans , N′Diaye Alimatou , Perronne Christian , Lienhardt Christian , McIlleron Helen , Fielding Katherine
Published: April 2017

The effects on ventricular repolarization—recorded on the electrocardiogram (ECG) as lengthening of the QT interval—of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; “control”) or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (
C
max
) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of −0.9% (95% confidence interval [CI], −2.0% to 2.3%;
P
= 0.12) and 0.1% (95% CI, −0.6% to 0.9%;
P
= 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, −1.4% to 3.1%;
P
= 0.47). No evidence was found of an association between
C
max
of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.)
Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073
Authors: Zhang Yinfeng , Clarke William , Marzinke Mark A. , Piwowar-Manning Estelle , Beauchamp Geetha , Breaud Autumn , Hendrix Craig W. , Cloherty Gavin A. , Emel Lynda , Rose Scott , Hightow-Weidman Lisa , Siegel Marc , Shoptaw Steven , Fields Sheldon D. , Wheeler Darrell , Eshleman Susan H.
Published: April 2017

Daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) is a safe and effective intervention for HIV preexposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs (multidrug assay) in assessing recent PrEP exposure (detection limit, 2 to 20 ng/ml). Samples were obtained from 216 Black men who have sex with men (208 HIV-uninfected men and 8 seroconverters) who were enrolled in a study in the United States evaluating the acceptability of TDF-FTC PrEP (165 of the uninfected men and 5 of the seroconverters accepted PrEP). Samples from 163 of the 165 HIV-uninfected men who accepted PrEP and samples from all 8 seroconverters were also tested for tenofovir (TFV) and FTC using a quantitative assay (detection limit for both drugs, 0.31 ng/ml). HIV drug resistance was assessed in seroconverter samples. The multidrug assay detected TFV and/or FTC in 3 (1.4%) of the 208 uninfected men at enrollment, 84 (40.4%) of the 208 uninfected men at the last study visit, and 1 (12.5%) of the 8 seroconverters. No other ARV drugs were detected. The quantitative assay confirmed all positive results from the multidrug assay and detected TFV and/or FTC in 9 additional samples (TFV range, 0.65 to 16.5 ng/ml; FTC range, 0.33 to 14.6 ng/ml). Resistance mutations were detected in 4 of the 8 seroconverter samples. The multidrug assay had 100% sensitivity and specificity for detecting TFV and FTC at drug concentrations consistent with daily PrEP use. The quantitative assay detected TFV and FTC at lower levels, which also might have provided protection against HIV infection.
Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureus
Authors: Elmwall Jonas , Kwiecinski Jakub , Na Manli , Ali Abukar Ahmed , Osla Veronica , Shaw Lindsey N. , Wang Wanzhong , Sävman Karin , Josefsson Elisabet , Bylund Johan , Jin Tao , Welin Amanda , Karlsson Anna
Published: April 2017

Staphylococcus aureusis a major cause of skin and soft tissue infection. The bacterium expresses four major proteases that are emerging as virulence factors: aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a β-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates ofS. aureuscaused galectin-3 degradation. Similar proteolytic capacities were found inStaphylococcus epidermidisisolates but not inStaphylococcus saprophyticus. Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by bacterium-derived proteolysis of galectin-3, and SspB was identified as the major protease responsible. The impact of galectin-3 and protease expression onS. aureusvirulence was studied in a murine skin infection model. In galectin-3+/+mice, SspB-expressingS. aureuscaused larger lesions and resulted in higher bacterial loads than protease-lacking bacteria. No such difference in bacterial load or lesion size was detected in galectin-3−/−mice, which overall showed smaller lesion sizes than the galectin-3+/+animals. In conclusion, the staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation of oxygen radical production in human neutrophils and increasing tissue damage during skin infection.
Cues from the Membrane: Bacterial Glycerophospholipids
Authors: Dalebroux Zachary D.
Published: April 2017

In this issue of the
Journal of Bacteriology
, V. W. Rowlett et al. unveil new
Escherichia coli
circuitry linking membrane glycerophospholipid (GPL) homeostasis to bacterial stress response and adaptation mechanisms (J Bacteriol 199:e00849-16, 2017,
https://doi.org/10.1128/JB.00849-16
). Glycerophospholipids comprise critical components of the dual-membrane envelope of Gram-negative bacteria and participate in many processes. The new evidence suggests that, in some instances, distinct
E. coli
GPL molecules function for distinct biochemistry and bacteria sense perturbations in membrane GPL concentrations to coordinate survival strategies. Understanding GPL sensing and remodeling mechanisms will be important moving forward, given the breadth of function for these molecules in bacteriology.
Pseudomonas aeruginosa-Derived Rhamnolipids and Other Detergents Modulate Colony Morphotype and Motility in the Burkholderia cepacia Complex
Authors: Bernier Steve P. , Hum Courtney , Li Xiang , O'Toole George A. , Magarvey Nathan A. , Surette Michael G.
Published: April 2017

Competitive interactions mediated by released chemicals (e.g., toxins) are prominent in multispecies communities, but the effects of these chemicals at subinhibitory concentrations on susceptible bacteria are poorly understood. Although
Pseudomonas aeruginosa
and species of the
Burkholderia cepacia
complex (Bcc) can exist together as a coinfection in cystic fibrosis airways,
P. aeruginosa
toxins can kill Bcc species
in vitro
. Consequently, these bacteria become an ideal
in vitro
model system to study the impact of sublethal levels of toxins on the biology of typical susceptible bacteria, such as the Bcc, when exposed to
P. aeruginosa
toxins. Using
P. aeruginosa
spent medium as a source of toxins, we showed that a small window of subinhibitory concentrations modulated the colony morphotype and swarming motility of some but not all tested Bcc strains, for which rhamnolipids were identified as the active molecule. Using a random transposon mutagenesis approach, we identified several genes required by the Bcc to respond to low concentrations of rhamnolipids and consequently affect the ability of this microbe to change its morphotype and swarm over surfaces. Among those genes identified were those coding for type IVb-Tad pili, which are often required for virulence in various bacterial pathogens. Our study demonstrates that manipulating chemical gradients
in vitro
can lead to the identification of bacterial behaviors relevant to polymicrobial infections.

IMPORTANCE
Interspecies interactions can have profound effects on the development and outcomes of polymicrobial infections. Consequently, improving the molecular understanding of these interactions could provide us with new insights on the possible long-term consequences of these chronic infections. In this study, we show that
P. aeruginosa
-derived rhamnolipids, which participate in Bcc killing at high concentrations, can also trigger biological responses in
Burkholderia
spp. at low concentrations. The modulation of potential virulence phenotypes in the Bcc by
P. aeruginosa
suggests that these interactions contribute to pathogenesis and disease severity in the context of polymicrobial infections.
Sports injuries and illnesses in first-year physical education teacher education students
Authors: van Beijsterveldt Anne-Marie , Richardson Angelo , Clarsen Benjamin , Stubbe Janine
Published: April 2017

Background/aim

We aimed to investigate the magnitude and characteristics of injuries and illnesses in Dutch physical education teacher education (PETE) students.

Methods

During the first 21 weeks of the academic year, 245 first-year students registered their health problems online using the Oslo Sports Trauma Research Centre (OSTRC) Questionnaire on Health Problems.

Results

A total of 276 injuries, 140 illnesses and 69 unclassified health problems were reported. We found an injury incidence rate of 11.7 injuries per 1000 hours (95% CI 10.4 to 13.2). Injury characteristics were: 42% overuse injuries, 62% causing absence from sports (median injury time loss=2 days) and 64% reinjuries. Most injuries were located at the knee, lower leg (anterior) and ankle. The duration of the illnesses was short (<1 week).

Summary and conclusions

We implemented a new registration method in the PETE academic programme. The results show that the risk for health problems is high for PETE students. Prevention is necessary, and to decrease injuries prevention programmes should focus on the lower extremities.
A novel treadmill protocol for exercise testing in children: the British Columbia Children’s Hospital protocol
Authors: Duff D Kathryn , De Souza Astrid M , Human Derek G , Potts James E , Harris Kevin C
Published: April 2017

Background

Exercise testing in children is widely recommended for a number of clinical and prescriptive reasons. Many institutions continue to use the Bruce protocol for treadmill testing; however, with its incremental changes in speed and grade, it has challenges for practical application in children. We have developed a novel institutional protocol (British Columbia Children’s Hospital (BCCH)), which may have better utility in paediatric populations.

Aim

To determine if our institutional protocol yields similar peak responses in minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), metabolic equivalents (METS) and heart rate (HR) when compared with the traditional Bruce protocol.

Methods

On two different occasions, 70 children (boys=33; girls=37) aged 10–18 years completed an exercise test on a treadmill using each of the protocols. During each test, metabolic gas exchange parameters were measured. HR was monitored continuously during exercise using an HR monitor.

Results

Physiological variables were similar between the two protocols (median (IQR); rs): VE (L/min) (BCCH=96.7 (72.0–110.2); Bruce=99.2 (75.6–120.0); rs=0.95), peak VO2(mL/min) (BCCH=2897 (2342–3807); Bruce=2901 (2427–3654); rs=0.94) and METS (BCCH=16.2 (14.8–17.7); Bruce=16.4 (14.7–17.9); rs=0.89). RERs were similar (BCCH=1.00 (0.96–1.02); Bruce=1.03 (0.99–1.07); rs=0.48). Total exercise time (in seconds) was longer for the BCCH protocol: BCCH=915 (829–1005); Bruce=810 (750-919); rs=0.67.

Conclusion

The BCCH protocol produces similar peak exercise responses to the Bruce protocol and provides an alternative for clinical exercise testing in children.
Flow diverter treatment of intracranial vertebral artery dissecting pseudoaneurysms
Authors: Cerejo Russell , Bain Mark , Moore Nina , Hardman Julian , Bauer Andrew , Hussain M Shazam , Masaryk Thomas , Rasmussen Peter , Toth Gabor
Published: April 2017

Introduction

Intracranial vertebral dissecting pseudoaneurysms are a rare, but increasingly recognized, cause of subarachnoid hemorrhage and ischemic stroke. The risks of aneurysm re-rupture and associated morbidity are high. The use of flow diverter stents for the treatment of these aneurysms has not been well studied.

Objective

To report our data and provide a summarized review of literature using flow diverter stents for the treatment of intracranial vertebral artery dissecting pseudoaneurysms.

Methods

We performed a retrospective analysis of flow diverter stents used for the treatment of intracranial vertebral artery dissecting pseudoaneurysms. Clinical, imaging, procedural, and follow-up data were collected.

Results

We identified eight vertebral dissecting pseudoaneurysms in seven patients (5 (71.4%) female; median age 47 years (IQR 46–52)) who had undergone treatment with flow diverter stents. In 4/7 patients (57.1%) the aneurysm had ruptured; however, only one was treated in the acute phase. Median size of the largest diameter of the aneurysm was 6.3 mm (IQR 4.2–8.8), and 7/8 aneurysms (87.5%) were treated with a single flow diverter device. Three aneurysms were concurrently coiled. Angiographic complete occlusion was seen in 6/8 (75%) aneurysms at a median follow-up of 14 months (IQR 7.7–20.2). Two patients had periprocedural strokes with transient neurologic deficits. All patients had a good clinical outcome (modified Rankin Scale score ≤2). There were no re-treatments or aneurysm ruptures during the follow-up period.

Conclusions

Our experience suggests that flow diverter stent treatment of intracranial vertebral artery dissecting pseudoaneurysms is safe, and associated with good occlusion rates and favorable clinical outcomes.
Superstructure–foundation interaction in multi-objective pile group optimization considering settlement response
Authors: Leung Y.F. , Klar A. , Soga K. , Hoult N.A.
Published: April 2017

The full potential of pile optimization has not been realized as the interactions between superstructures and foundations, and the relationships between material usage and foundation performance are rarely investigated. This paper introduces an analysis and optimization approach for pile group and piled raft foundations, which allows coupling of superstructure stiffness with the foundation model, through a condensed matrix representing the flexural characteristics of the superstructure. This coupled approach is implemented within a multi-objective optimization algorithm, capable of providing a series of optimized pile configurations at various amounts of material. The approach is illustrated through two case studies. The first case involves evaluation of the coupled superstructure–foundation analyses against field measurements of a piled raft–supported building in London, UK. The potential benefits of pile optimization are also demonstrated through re-analyses of the foundation by the proposed optimization approach. In the second case, the effects of a soft storey on the superstructure–foundation interactions are investigated. These cases demonstrate the importance of properly considering the superstructure effects, especially when the building consists of stiff components such as concrete shear walls. The proposed approach also allows engineers to make informed decisions on the foundation design, depending on the specific project finances and performance requirements.
Obtaining nonvanishing 𝜃13 with constrained neutrino Yukawa matrix and implications for flavor model buildings
Authors: Zhao Ya
Published: April 2017

Assuming a diagonal Majorana neutrino mass matrix, we investigate the neutrino Yukawa textures which lead to a nonzero reactor mixing angle [Formula: see text]. The neutrino effective coupling matrix [Formula: see text] is pre-diagonalized by a constant mixing pattern [Formula: see text] with a vanishing [Formula: see text]. The resulting pre-diagonal symmetrical matrix [Formula: see text] is set to be four texture zeros with two types of off-diagonal elements nonzero, which are [Formula: see text] and [Formula: see text], respectively. With the expectation of simple textures, we thoroughly classify the linear combinations, [Formula: see text], [Formula: see text] and [Formula: see text] of Yukawa elements [Formula: see text] in the same row, according to the values, vanishing or not. Each set of the classifications can lead to a Yukawa texture which may have implications for the discrete flavor model buildings. We also present a model based on [Formula: see text] according to one set of the constraints on the three combinations with a specific choice of a coefficient in Yukawa texture.
Inflation of universe due to nonlinear electrodynamics
Authors: Kruglov S. I.
Published: April 2017

A model of nonlinear electrodynamics with a dimensional parameter [Formula: see text] is considered. Electromagnetic fields are the source of the gravitation field and inflation of the universe. We imply that the universe is filled by stochastic magnetic fields. It is demonstrated that after the universe inflation the universe decelerates approaching the Minkowski space–time. We evaluate the spectral index, the tensor-to-scalar ratio, and the running of the spectral index which approximately agree with the Planck and WMAP data.
Fe–6.5% Si/SiO2 powder cores prepared by spark plasma sintering: Magnetic properties and sintering mechanism
Authors: Xu Lili , Yan Biao
Published: April 2017

The Fe–6.5% Si/SiO2 powder cores were prepared by dry-type stirring ball milling and subsequent spark plasma sintering (SPS). Microstructure, magnetic properties and sintering mechanism of Fe–6.5% Si/SiO2 powder core were investigated. The experimental result indicated that Fe–6.5% Si particles were perfectly surrounded by SiO2 insulating layer with cristobalite structure. Compared with Fe–6.5% Si powder core, Fe–6.5% Si/SiO2 powder core has 20 times higher electrical resistivity ([Formula: see text]) and maintained excellent soft magnetic properties ([Formula: see text] emu/g, [Formula: see text] Oe). Core losses decreased to nearly 1/10 of those of Fe–6.5% Si powder core due to the insulation effect of SiO2 particles. Sintering mechanisms of Fe–6.5% Si/SiO2 core-shell powders during spark plasma sintering are proposed on the basis of high electrical resistivity (easy to heat) and pin effects (easy to discharge) of SiO2 particles.
The effect of strain rates on tensile deformation of ultrafine-grained copper
Authors: Li M. , Jiang Q. W.
Published: April 2017

Tensile deformation behavior of ultrafine-grained (UFG) copper processed by accumulative roll-bonding (ARB) was studied under different strain rates at room temperature. It was found that the UFG copper under the strain rate of 10[Formula: see text] s[Formula: see text] led to a higher strength (higher flow stress level), flow stability (higher stress hardening rate) and fracture elongation. In the fracture surface of the sample appeared a large number of cleavage steps under the strain rate of 10[Formula: see text] s[Formula: see text], indicating a typical brittle fracture mode. When the strain rate is 10[Formula: see text] or 10[Formula: see text] s[Formula: see text], a great amount of dimples with few cleavage steps were observed, showing a transition from brittle to plastic deformation with increasing strain rate.
Process optimization of rolling for zincked sheet technology using response surface methodology and genetic algorithm
Authors: Ji Liang-Bo , Chen Fang
Published: April 2017

Numerical simulation and intelligent optimization technology were adopted for rolling and extrusion of zincked sheet. By response surface methodology (RSM), genetic algorithm (GA) and data processing technology, an efficient optimization of process parameters for rolling of zincked sheet was investigated. The influence trend of roller gap, rolling speed and friction factor effects on reduction rate and plate shortening rate were analyzed firstly. Then a predictive response surface model for comprehensive quality index of part was created using RSM. Simulated and predicted values were compared. Through genetic algorithm method, the optimal process parameters for the forming of rolling were solved. They were verified and the optimum process parameters of rolling were obtained. It is feasible and effective.