bluuebunny/crossref_metadata_2025 huggingface dataset:
On the structure of Lipschitz-free spaces
Authors: Cúth Marek , Doucha Michal , Wojtaszczyk Przemysław
Published: February 2016

In this note we study the structure of Lipschitz-free Banach spaces. We show that every Lipschitz-free Banach space over an infinite metric space contains a complemented copy of

ℓ
1

\ell _1

. This result has many consequences for the structure of Lipschitz-free Banach spaces. Moreover, we give an example of a countable compact metric space

K
K

such that

F

(
K
)

\mathcal {F}(K)

is not isomorphic to a subspace of

L
1

L_1

and we show that whenever

M
M

is a subset of

R

n

\mathbb {R}^n

, then

F

(
M
)

\mathcal {F}(M)

is weakly sequentially complete; in particular,

c
0

c_0

does not embed into

F

(
M
)

\mathcal {F}(M)

.
Does Age Matter? Association Between Usual Source of Care and Hypertension Control in the US Population: Data From NHANES 2007–2012
Authors: Dinkler John M. , Sugar Catherine A. , Escarce José J. , Ong Michael K. , Mangione Carol M.
Published: February 2016

BACKGROUND

The positive role of having a usual source of care (USOC) on the receipt of preventative services is known. However, associations between USOC and hypertension control and the differential association across age groups is unknown in the US population.

METHODS

We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Multivariable logistic regression was used to evaluate the association between having a USOC and hypertension control. The differential effect of USOC on hypertension control by age was assessed using predicted marginal effects across age groups in the multivariable logistic model.

RESULTS

In adjusted analyses, those with a USOC had higher odds of hypertension control (odds ratio = 3.89, 95% confidence interval (CI): 2.15–6.98). The marginal effect of having a USOC is associated with a 30 percentage point higher probability of controlled blood pressure compared to those without a USOC (marginal probability = 0.30, 95% CI: 0.19–0.41). The marginal effect of USOC on hypertension control varied by age groups, with a statistically significantly lower marginal effect of USOC on hypertension seen among those older than 74 years of age (marginal probability = 0.27, 95% CI: 0.18–0.36) and younger than 35 years of age (marginal probability = 0.23, 95% CI: 0.14–0.33).

CONCLUSION

Having a USOC is significantly associated with improved hypertension control in the US population. The variation in the association across age groups has important implications in targeting age-specific antihypertensive strategies to reduce the burden of hypertension in the US population.
Prognostic Value of C-Reactive Protein in Resistant
Hypertension
Authors: Cortez Arthur Fernandes , Muxfeldt Elizabeth Silaid , Cardoso Claudia Regina Lopes , Salles Gil Fernando
Published: February 2016

BACKGROUND

C-reactive protein (CRP) is a biomarker of systemic low-grade inflammation and a cardiovascular risk predictor in several clinical conditions. However, its prognostic value has never been examined in patients with resistant hypertension.

METHODS

In a prospective study, 476 patients with resistant hypertension had CRP levels measured at baseline, together with other clinical laboratory variables, including ambulatory blood pressures (BPs). Primary end points were a composite of major fatal or nonfatal cardiovascular events, all-cause mortality, and cardiovascular mortality. Multiple Cox regression assessed the associations between CRP levels and end points.

RESULTS

Median CRP was 3.8mg/l (interquartile range: 2.0–7.2mg/l). After a median follow-up of 9 years, 103 major cardiovascular events occurred, and 120 patients died, 62 from cardiovascular causes. Patients with CRP levels above the median value had a doubled excess risk of major cardiovascular events (95% confidence interval: 1.29–3.06; P = 0.002) and an 86% higher risk of cardiovascular death (95% confidence interval: 1.07–3.25; P = 0.029), after adjustments for potential confounders including traditional cardiovascular risk factors and ambulatory BP and dipping pattern. A high CRP equally predicted coronary (hazard ratio: 2.04; 95% confidence interval: 1.10–3.76; P = 0.023) and cerebrovascular events (hazard ratio: 2.72; 95% confidence interval: 1.30–5.67; P = 0.007). In interaction and sensitivity analyses, CRP levels were stronger predictors of worse cardiovascular outcomes in younger and obese patients, and in those with uncontrolled ambulatory BPs and with the nondipping pattern.

CONCLUSIONS

In patients with resistant hypertension, elevated serum CRP levels is predictive of worse cardiovascular prognosis above and beyond other cardiovascular risk factors, including ambulatory BP levels and dipping patterns.
Spin properties of supermassive black holes with powerful outflows
Authors: Daly Ruth. A.
Published: February 2016

Relationships between beam power and accretion disc luminosity are studied for a sample of 55 high excitation radio galaxies (HERG), 13 low excitation radio galaxies (LERG), and 29 radio loud quasars (RLQ) with powerful outflows. The ratio of beam power to disc luminosity tends to be high for LERG, low for RLQ, and spans the full range of values for HERG. Writing general expressions for the disc luminosity and beam power and applying the empirically determined relationships allows a function that parametrizes the spins of the holes to be estimated. Interestingly, one of the solutions that is consistent with the data has a functional form that is remarkably similar to that expected in the generalized Blandford–Znajek model with a magnetic field that is similar in form to that expected in magnetically arrested disk (MAD) and advection-dominated accretion flow (ADAF) models. Values of the spin function, obtained independent of specific outflow models, suggest that spin and active galactic nucleus type are not related for these types of sources. The spin function can be used to solve for black hole spin in the context of particular outflow models, and one example is provided.
Identification of Novel Virulence-Associated Proteins Secreted to Xylem by Verticillium nonalfalfae During Colonization of Hop Plants
Authors: Flajsman Marko , Mandelc Stanislav , Radisek Sebastjan , Stajner Natasa , Jakse Jernej , Kosmelj Katarina , Javornik Branka
Published: February 2016

Plant pathogens employ various secreted proteins to suppress host immunity for their successful host colonization. Identification and characterization of pathogen-secreted proteins can contribute to an understanding of the pathogenicity mechanism and help in disease control. We used proteomics to search for proteins secreted to xylem by the vascular pathogen Verticillium nonalfalfae during colonization of hop plants. Three highly abundant fungal proteins were identified: two enzymes, α-N-arabinofuranosidase (VnaAbf4.216) and peroxidase (VnaPRX1.1277), and one small secreted hypothetical protein (VnaSSP4.2). These are the first secreted proteins so far identified in xylem sap following infection with Verticillium spp. VnaPRX1.1277, classified as a heme-containing peroxidase from Class II, similar to other Verticillium spp. lignin-degrading peroxidases, and VnaSSP4.2, a 14-kDa cysteine-containing protein with unknown function and with a close homolog in related V. alfalfae strains, were further examined. The in planta expression of VnaPRX1.1277 and VnaSSP4.2 genes increased with the progression of colonization, implicating their role in fungal virulence. Indeed, V. nonalfalfae deletion mutants of both genes exhibited attenuated virulence on hop plants, which returned to the level of the wild-type pathogenicity in the knockout complementation lines, supporting VnaPRX1.1277 and VnaSSP4.2 as virulence factors required to promote V. nonalfalfae colonization of hop plants.
Geosmithia morbida Found on Weevil Species Stenomimus pallidus in Indiana
Authors: Juzwik Jennifer , Banik Mark T. , Reed Sharon E. , English James T. , Ginzel Matthew D.
Published: February 2016

The canker pathogen Geosmithia morbida is known to be transmitted to Juglans species by the bark beetle Pityophthorus juglandis, and to lead to development of thousand cankers disease. In an Indiana-wide trap-tree survey of ambrosia and bark beetles and weevils colonizing stressed Juglans nigra, G. morbida was detected on three Stenomimus pallidus weevils emerged from two trees on one site. This is the first report of the pathogen in Indiana and the first report of the fungus from an insect species other than P. juglandis.

Accepted for publication 22 October 2014. Published 12 January 2015.
Bismerthiazol Inhibits Xanthomonas citri subsp. citri Growth and Induces Differential Expression of Citrus Defense-Related Genes
Authors: Yu Xiaoyue , Armstrong Cheryl M. , Zhou Mingguo , Duan Yongping
Published: February 2016

Citrus canker, caused by Xanthomonas citri ssp. citri, is a serious disease that causes substantial economic losses to the citrus industry worldwide. The bactericide bismerthiazol has been used to control rice bacterial blight (X. oryzae pv. oryzae). In this paper, we demonstrate that bismerthiazol can effectively control citrus canker by both inhibiting the growth of X. citri ssp. citri and triggering the plant’s host defense response through the expression of several pathogenesis-related genes (PR1, PR2, CHI, and RpRd1) and the nonexpresser of PR genes (NPR1, NPR2, and NPR3) in ‘Duncan’ grapefruit, especially at early treatment times. In addition, we found that bismerthiazol induced the expression of the marker genes CitCHS and CitCHI in the flavonoid pathway and the PAL1 (phenylalanine ammonia lyase 1) gene in the salicylic acid (SA) biosynthesis pathway at different time points. Moreover, bismerthiazol also induced the expression of the priming defense-associated gene AZI1. Taken together, these results indicate that the induction of the defense response in ‘Duncan’ grapefruit by bismerthiazol may involve the SA signaling pathway and the priming defense and that bismerthiazol may serve as an alternative to copper bactericides for the control of citrus canker.
Silent Bias: Challenges, Obstacles, and Strategies for Leadership Development in Academic Medicine—Lessons From Oral Histories of Women Professors at the University of Kansas
Authors: Pingleton Susan K. , Jones Emily V.M. , Rosolowski Tacey A. , Zimmerman Mary K.
Published: February 2016

Purpose

Despite dramatic increases in female learners and junior faculty, a significant gap remains in female leadership in academic medicine. To assess challenges and obstacles encountered, strategies for academic success, and lessons learned for leadership development, the authors conducted an in-depth study of women full professors.

Method

The authors used a qualitative oral history approach, interviewing 87% of the cohort of female full professors at one Midwestern medical school in 2013 using a pretested, open-ended, semistructured interview guide. Interviews were videotaped and the audio recordings transcribed. Content was sorted into categories and key themes identified within each category.

Results

Participants described significant challenges: being treated with “silent bias,” “being ignored,” and being seen as an “other.” Coping strategies included downplaying, keeping a distance, employing humor, and using symbols (e.g., white coat) to carefully present themselves. Explanations for success included intelligence, meritocracy, being even-tempered, and carefully constructing femininity. The participants recommended individual skills and actions to prepare for leadership development. Virtually all women could describe an individual mentor (sponsor), usually male, who provided essential assistance for their career success. At the same time, they stressed the importance of institutional support for diversity, especially with child care.

Conclusions

Attaining “full professor” status is the pinnacle of academic success. Women who successfully navigated this academic ladder describe significant external and internal challenges that require multiple strategies to overcome. Leadership development entails a combination of individual support through mentors and sponsors, self-education and reflection, and organizational structural support to promote diversity.
Tumor Growth Kinetics Before and After First-line Chemotherapy in Metastatic Castration-resistant Prostate Cancer
Authors: Colloca Giuseppe , Venturino Antonella , Guarneri Domenico
Published: February 2016

Objectives:

The role of the tumor growth fraction has been investigated poorly in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess whether some prostate-specific antigen (PSA)-related variables of tumor cell kinetics predict the overall survival in early and late mCRPC, and to explore changes in the tumor growth fraction after chemotherapy.

Methods:

A retrospective analysis of 3 tumor cell kinetic variables in patients with mCRPC receiving first-line chemotherapy has been performed. The PSA-related tumor growth rate, the log ratio, and the tumor response have been measured at 3 different times. A further analysis has been performed after stratification by the Gleason score and chemotherapy. Finally, tumor growth after progression to chemotherapy has been explored.

Results:

G at castration resistance is significantly associated with survival after chemotherapy among patients with a low Gleason score (r=−0.650, P-value=0.022). At the time of first-line chemotherapy, both G and PSA response rates report a significant relationship with survival. At the time of postchemotherapy progression, only the G after 12 weeks of chemotherapy maintains a relationship with survival in patients with a low Gleason score (r=−0.483, P-value=0.023); in particular, a tumor growth rate <−0.5%/day appears to be associated with a poor postprogression survival. Despite the lack of correlation between postprogression G and postprogression survival, the response to chemotherapy defines 2 groups with different growth characteristics.

Conclusions:

Among patients with mCRPC, tumor cell kinetics appears to be able to predict the outcome, especially in tumors with a low Gleason score.
Phase I Trial of Dose-escalated Whole Liver Irradiation With Hepatic Arterial Fluorodeoxyuridine/Leucovorin and Streptozotocin Followed by Fluorodeoxyuridine/Leucovorin and Chemoembolization for Patients With Neuroendocrine Hepatic Metastases
Authors: Shilkrut Mark , Sapir Eli , Hanasoge Sheela , Schipper Matthew J. , Normolle Daniel P. , Ben-Josef Edgar , Ensminger William , Lawrence Theodore S. , Feng Mary
Published: February 2016

Objectives:

We have previously shown that refractory neuroendocrine tumors can respond to moderate doses of chemoradiotherapy. We completed a dose-escalation phase I/II trial combining hepatic arterial (HA) chemotherapy, chemoembolization, and dose-escalated whole liver radiotherapy to determine the maximum safe dose of radiation that could be delivered and to make a preliminary assessment of response.

Materials and Methods:

From 2002 to 2009, 19 patients with symptomatic neuroendocrine liver metastases who failed somatostatin analog therapy were enrolled. HA fluorodeoxyuridine, leucovorin, and streptozotocin were delivered, as concurrent whole liver radiotherapy was dose escalated from 24 to 32 Gy in 2 Gy fractions, with a target rate of dose-limiting grade ≥3 radiation-induced liver disease of 10%. Eight weeks later, for patients without grade ≥3 liver or grade ≥4 any toxicity, a 72-hour infusion of HA fluorodeoxyuridine and leucovorin was given, followed by transarterial chemoembolization.

Results:

Eleven patients completed the entire protocol and received 24 to 32 Gy. No patients developed radiation-induced liver disease; 7 had grade 3 to 4 transiently increased liver function tests, and 4 had other grade 4 toxicities. Three patients (14%) had partial response, 16 (84%) stable disease. Median freedom from local progression and overall survival were 35.3 and 54.6 months, respectively.

Conclusions:

Thirty-two in 2 Gy daily fractions can be delivered safely when combined with HA chemotherapy and subsequent transarterial chemoembolization. However, although objective responses were observed, this combination was not significantly better than our prior approaches. Further treatment intensification strategies, including individualized dose escalation for radiation-tolerant livers, and improved radiosensitization should be investigated, along with improved systemic therapy.
Use of Risk Stratification Tools to Enhance Antimicrobial Stewardship Practices
Authors: Martin Kelly E. , Roshdy Danya , Kasbekar Rupal , Pasquale Timothy R.
Published: February 2016

Antimicrobial stewardship is an important strategic initiative to ensure patient safety and antimicrobial efficacy. National guidelines advocate the utilization of guidelines and clinical pathways as effective stewardship strategies to enhance the appropriate selection of antimicrobial treatment regimens. This article reviews 3 algorithms using risk stratification techniques implemented within our organization: treatment of acute bacterial skin and skin structure infections, febrile neutropenia, and Clostridium difficile infection. The relevant literature surrounding the utilization of risk stratification tools and applications to other disease states will also be reviewed. Further studies are warranted to evaluate the impact of risk stratification tools on patient outcomes.
Mycobacterium abscessus
Authors: Husson Jennifer , Saleeb Paul , Amoroso Anthony
Published: February 2016

Mycobacterium (M.) abscessus is an increasingly important pathogen in lung transplant recipients. Due to difficulty in accurately identifying M. abscessus from M. fortuitum–chelonae complex, appropriate treatment may be delayed. We present a case of misidentification of M. abscessus in a lung transplant recipient, which contributed to the patient's suboptimal therapy and eventual death. This case highlights the importance of accurate identification for appropriate treatment of M. abscessus in lung transplant recipients.
Use of Intra-Articular Clindamycin in the Treatment of Prosthetic Joint Infections With Bacteroides fragilis in a Patient with Sickle Cell Disease
Authors: Antony Suresh Jude
Published: February 2016

Use of intra-articular antibiotics to treat prosthetic joint infections is becoming an increasingly viable option, especially in patients with a history of multidrug-resistant bacteria and multiple comorbidities where the risk of multiple surgeries is high. At this time, there does not exist a standard antibiotic regimen and or dosing to treat various infections. The risk of prolonged intravenous antibiotics and Clostridium difficile remains high in this group of patients, especially when one has to use clindamycin as a drug of choice. We present a 17-year-old African American female with Bacteroides fragilis infection of a total hip arthroplasty, which was treated with intra-articular clindamycin with success.
Visual Dysfunctions at Different Stages after Blast and Non-blast Mild Traumatic Brain Injury
Authors: Capó-Aponte José E. , Jorgensen-Wagers Kendra L. , Sosa Josue A. , Walsh David V. , Goodrich Gregory L. , Temme Leonard A. , Riggs Daniel W.
Published: February 2016

Purpose

To assess the prevalence of visual dysfunctions and associated symptoms in war fighters at different stages after non–blast- or blast-induced mild traumatic brain injury (mTBI).

Methods

A comprehensive retrospective review of the electronic health records of 500 U.S. military personnel with a diagnosis of deployment-related mTBI who received eye care at the Landstuhl Regional Medical Center. For analysis, the data were grouped by mechanism of injury, and each group was further divided in three subgroups based on the number of days between injury and initial eye examination.

Results

The data showed a high frequency of visual symptoms and visual dysfunctions. However, the prevalence of visual symptoms and visual dysfunctions did not differ significantly between mechanism of injury and postinjury stage, except for eye pain and diplopia. Among visual symptoms, binocular dysfunctions were more common, including higher near vertical phoria, reduced negative fusional vergence break at near, receded near point of convergence, decreased stereoacuity, and reduced positive relative accommodation.

Conclusions

The lack of difference in terms of visual sequelae between subgroups (blast vs. nonblast) suggests that research addressing the assessment and management of mTBI visual sequelae resulting from civilian nonblast events is relevant to military personnel where combat injury results primarily from a blast event.
Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021
Authors: Ruan Alexandra , Tobin Nicole H. , Mulligan Kathleen , Rollie Adrienne , Li Fan , Sleasman John , Aldrovandi Grace M.
Published: February 2016

Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss.
Rates of Cancers and Opportunistic Infections in Patients With Psoriatic Arthritis Compared With Patients Without Psoriatic Arthritis
Authors: Hagberg Katrina Wilcox , Li Lin , Peng Michael , Paris Maria , Shah Kamal , Jick Susan S.
Published: February 2016

Objectives

This study aimed to estimate rates of cancer or opportunistic infection in patients with psoriatic arthritis (PsA) compared with patients without PsA.

Methods

Using the Clinical Practice Research Datalink, we conducted a cohort study of patients with a PsA diagnosis and patients without such diagnosis, matched on age, sex, general practice, and calendar time, to assess the incidence of cancers (solid, hematologic, and nonmelanoma skin cancer) and opportunistic infections. We estimated incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) for each outcome and stratified results in the PsA cohort by receipt of systemic PsA drugs.

Results

The rate of hematologic cancer was slightly higher in the PsA cohort compared with the non-PsA cohort (IRR, 1.52; 95% CI, 1.10–2.10), whereas the rates of solid cancer and of nonmelanoma skin cancer were similar between the PsA and non-PsA cohorts (IRR, 1.01; 95% CI, 0.90–1.13; and IRR, 0.97; 95% CI, 0.82–1.14, respectively). Incidence rates were higher for PsA patients who received prescriptions for PsA drugs compared with those who did not. The IRs for infection were higher in the PsA compared with the non-PsA cohort (IRR, 1.39; 95% CI, 1.31–1.47) and were significantly higher in patients who received prescriptions (IRR, 1.71; 95% CI, 1.52–1.91).

Conclusions

The rates of solid and nonmelanoma skin cancers were similar in patients with PsA compared with patients without PsA, but the rates of hematologic cancer and opportunistic infections were higher in patients with PsA. In patients with PsA, rates of all outcomes were higher among those who received prescriptions for systemic PsA therapy.
Liver Imaging Reporting and Data System v2014 With Gadoxetate Disodium–Enhanced Magnetic Resonance Imaging
Authors: Choi Sang Hyun , Byun Jae Ho , Kim So Yeon , Lee So Jung , Won Hyung Jin , Shin Yong Moon , Kim Pyo Nyun
Published: February 2016

Objectives

The aim of this study was to validate the Liver Imaging Reporting and Data System (LI-RADS) v2014 category 4 (LR-4) and 5 (LR-5) criteria on gadoxetate disodium–enhanced magnetic resonance imaging (MRI) in patients with chronic liver disease.

Materials and Methods

Between January and December 2012, 300 patients with chronic liver disease who had hepatic nodules 3.0 cm or smaller at surveillance ultrasonography and gadoxetate disodium–enhanced MRI were included. LI-RADS category was retrospectively assigned to each nodule on MRI. Final diagnosis was assessed using pathologic diagnosis only (operation or core-needle biopsy) or pathologic and clinical diagnosis (marginal recurrence after treatment or a change in lesion size on follow-up imaging). To validate the LR-4 and LR-5 criteria, the sensitivity, positive predictive value (PPV), and false referral rate for diagnosing hepatocellular carcinoma were examined.

Results

Based on major imaging features only, 137 nodules were initially assigned as LR-3, but 133 (97.1%) were upgraded into LR-4 by the presence of ancillary features. Excluding the remaining 4 LR-3 and 3 LR-M nodules, we analyzed 379 nodules in 294 patients, consisting of 211 LR-4 and 168 LR-5 nodules. Using pathologic diagnosis only, the sensitivity and PPV with 95% confidence intervals (CIs) for LR-5 were higher than those for LR-4 (57.3% [50.6–63.7] vs 42.7% [36.3–49.4]; 94.6% [89.0–97.5] vs 82.0% [73.7–88.1]), with a lower false referral rate (5.4% [2.5–11.0] vs 18.0% [11.9–26.3]). Using pathologic and clinical diagnosis, PPV and 95% CI for LR-5 were higher than that for LR-4 (95.2% [90.7–97.7] vs 79.1% [73.1–84.1]), whereas sensitivity and 95% CI for LR-5 was similar to that for LR-4 (48.9% [43.6–54.3] vs 51.1% [45.7–56.4]).

Conclusions

In patients with chronic liver disease, LR-5 criteria on gadoxetate disodium–enhanced MRI had excellent PPV for diagnosing hepatocellular carcinoma, whereas LR-4 criteria showed good PPV, but are only of limited use.
Effectiveness of performance appraisal
Authors: Ikramullah Malik , Van Prooijen Jan-Willem , Iqbal Muhammad Zahid , Ul-Hassan Faqir Sajjad
Published: February 2016

Purpose

– The purpose of this paper is to develop a conceptual framework for the effectiveness of performance appraisal (PA) systems by using a competing values approach.

Design/methodology/approach

– The review employs a three-step approach: first, the paper discusses the existing criteria to determine the effectiveness of PA systems, and presents criticisms of these criteria. Second, the paper reviews the literature on the competing values model of organizational effectiveness. Third, the paper integrates the PA system in the competing values model to develop a comprehensive framework for the effectiveness of PA systems.

Findings

– A practical model is developed, taking into account the processes and procedures involved in PA systems.

Originality/value

– The paper is designed to provide a guideline for managers to consider the effectiveness of a PA system. The paper suggests that assessing the effectiveness of a PA system on any single criterion ignores various important aspects of the system. Moreover, the effectiveness of a PA system should be based on the values and preferences of all major stakeholders of the system, i.e., appraisers, appraisees and the organization.
Thermodynamic Analysis of a Novel Space Heating System Featuring Hot Gas Water Technology
Authors: Reykers Robbe , Keersmaekers Raf , Ozalp Nesrin , Collaert Johan
Published: February 2016

Low operating cost, comfort, sustainability, and environmental footprint are the key elements of robust space heating (SH) system. In quest for higher efficiencies, it is not always possible to meet all of these demands where environmental footprint often gets secondary attention. This paper presents a novel SH system which is capable of meeting all of the aforementioned elements while simultaneously proving SH and domestic hot water (DHW). The system comprises a geothermal sourced heat pump (HP) featuring “hot gas water” (HGW) technology which delivers higher efficiency. This paper gives a thorough thermodynamic assessment of the system covering component based first and second law analysis and provides test results based on two case studies at a house (W10/W35) and a renovated building (W10/W45). The results show that a theoretical efficiency gain by 11.02% is achievable where the source temperature is 10 °C and the water temperature for floor heating is 35 °C. For the same system, with the same source temperature but with a supply temperature of 45 °C for SH, an efficiency gain of 17.91% is achievable. From experimental testing of the system using the test stand at GeoTherma, 4.73% efficiency gain with water temperature of 35 °C and 3.59% efficiency gain with water temperature of 45 °C were obtained. Economic analysis results showed that savings of up to 10% on an annual basis is possible with HGW technology installed in an average family house, whereas it gets 4.36% for a small hotel with a payback time period of about 9 yrs.
Techno-Economic Analysis of Solar Cooling Systems for Residential
Buildings in Italy
Authors: Vasta Salvatore , Palomba Valeria , Frazzica Andrea , Di Bella Guido , Freni Angelo
Published: February 2016

Solar cooling systems might represent a viable alternative for space cooling in residential buildings because the peak of cooling demand matches the availability of solar radiation. The use of adsorption chillers in this field gives another environmental benefit, since they employ natural refrigerants as water. However, the design of such systems is critical because it relates to several parameters and cannot be easily accomplished using traditional tools. In this work, a dynamic model for the simulation of a small solar cooling system employing adsorption chillers has been evaluated. The model, realized with the commercial software trnsys, has been implemented to quantify the effect of different operational and design parameters on the overall performances of solar cooling systems in three different Italian cities (Milan, Rome, and Messina). Particular focus was put on the comparison of different heat rejection systems, which was found to be a critical aspect in the design of such systems. In addition, an economic analysis has been performed for an optimized system, in order to evaluate the payback time of the systems compared to a traditional air conditioning system and provide indication on the possible outlooks by means of a sensitivity analysis.
A novel electron accelerator for MRI‐Linac radiotherapy
Authors: Whelan Brendan , Gierman Stephen , Holloway Lois , Schmerge John , Keall Paul , Fahrig Rebecca
Published: February 2016

Purpose:

MRI guided radiotherapy is a rapidly growing field; however, current electron accelerators are not designed to operate in the magnetic fringe fields of MRI scanners. As such, current MRI‐Linac systems require magnetic shielding, which can degrade MR image quality and limit system flexibility. The purpose of this work was to develop and test a novel medical electron accelerator concept which is inherently robust to operation within magnetic fields for in‐line MRI‐Linac systems.

Methods:

Computational simulations were utilized to model the accelerator, including the thermionic emission process, the electromagnetic fields within the accelerating structure, and resulting particle trajectories through these fields. The spatial and energy characteristics of the electron beam were quantified at the accelerator target and compared to published data for conventional accelerators. The model was then coupled to the fields from a simulated 1 T superconducting magnet and solved for cathode to isocenter distances between 1.0 and 2.4 m; the impact on the electron beam was quantified.

Results:

For the zero field solution, the average current at the target was 146.3 mA, with a median energy of 5.8 MeV (interquartile spread of 0.1 MeV), and a spot size diameter of 1.5 mm full‐width‐tenth‐maximum. Such an electron beam is suitable for therapy, comparing favorably to published data for conventional systems. The simulated accelerator showed increased robustness to operation in in‐line magnetic fields, with a maximum current loss of 3% compared to 85% for a conventional system in the same magnetic fields.

Conclusions:

Computational simulations suggest that replacing conventional DC electron sources with a RF based source could be used to develop medical electron accelerators which are robust to operation in in‐line magnetic fields. This would enable the development of MRI‐Linac systems with no magnetic shielding around the Linac and reduce the requirements for optimization of magnetic fringe field, simplify design of the high‐field magnet, and increase system flexibility.
Mothers and Fathers Both Matter: The Positive Influence of Parental Physical Activity Modeling on Children’s Leisure-Time Physical Activity
Authors: Schoeppe Stephanie , Röbl Markus , Liersch Sebastian , Krauth Christian , Walter Ulla
Published: February 2016

Purpose:

To investigate associations between maternal and paternal sport participation, and children’s leisure-time physical activity, and to explore differences by child gender.

Method:

The sample comprised 737 year five students (mean age: 11.0 ± 0.6 years, 52% male) recruited through the Fit for Pisa Project which was conducted in 2008 at 6 secondary schools in Goettingen, Germany. Maternal and paternal sport participation were assessed through child reports of mothers’ and fathers’ weekly participation in sport. Children’s leisure-time physical activity was measured as minutes/week that children engaged in organized and nonorganized sport. Multiple linear regression was used to assess associations between maternal and paternal sport participation, and children’s leisure-time physical activity.

Results:

Both maternal and paternal sport participation were positively associated with children’s leisure-time physical activity (maternal: b = 34.20, p < .001; paternal: b = 25.32, p < .05). When stratifying analyses by child gender, maternal sport participation remained significantly associated with leisure-time physical activity in girls (b = 60.64, p < .001). In contrast, paternal sport participation remained significantly associated with leisure-time physical activity in boys (b = 43.88, p < .01).

Conclusion:

Both maternal and paternal modeling positively influence children’s leisure-time physical activity.
Pharmacokinetics and Concentration-Dependent Efficacy of Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis
Authors: Petraitis Vidmantas , Petraitiene Ruta , Moradi Patriss W. , Strauss Gittel E. , Katragkou Aspasia , Kovanda Laura L. , Hope William W. , Walsh Thomas J.
Published: February 2016

We studied the pharmacokinetics and efficacy of the broad-spectrum triazole isavuconazole for the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Treatment started 24 h after endotracheal administration of
Aspergillus fumigatus
inoculum; study subjects included rabbits receiving orally administered prodrug isavuconazonium sulfate (BAL8557) equivalent to active moiety isavuconazole (ISA; BAL4815) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg (of body weight)/day, with an initial loading dose of 90 mg/kg (ISA90), and untreated rabbits (UC). There were significant concentration-dependent reductions of residual fungal burden (log CFU/gram) and of organism-mediated pulmonary injury, lung weights, and pulmonary infarct scores in ISA40- and ISA60-treated rabbits in comparison to those of UC (
P
< 0.001). ISA20-treated (
P
< 0.05), ISA40-treated, and ISA60-treated (
P
< 0.001) rabbits demonstrated significantly prolonged survival in comparison to that of UC. ISA40- and ISA60-treated animals demonstrated a significant decline of serum (1→3)-β-
d
-glucan levels (
P
< 0.05) and galactomannan indices (GMIs) during therapy following day 4 in comparison to progressive GMIs of UC (
P
< 0.01). There also were significantly lower concentration-dependent GMIs in bronchoalveolar lavage (BAL) fluid from ISA40- and ISA60-treated rabbits (
P
< 0.001). There was a direct correlation between isavuconazole plasma area under the concentration-time curve from 0 to 24 h (AUC
0–24
) and residual fungal burdens in lung tissues, pulmonary infarct scores, and total lung weights. In summary, rabbits treated with isavuconazole at 40 and 60 mg/kg/day demonstrated significant dose-dependent reduction of residual fungal burden, decreased pulmonary injury, prolonged survival, lower GMIs in serum and BAL fluid, and lower serum (1→3)-β-
d
-glucan levels.
Carbapenem- and Colistin-Resistant Enterobacter cloacae from Delta, Colorado, in 2015
Authors: Norgan Andrew P. , Freese Jarred M. , Tuin Patricia M. , Cunningham Scott A. , Jeraldo Patricio R. , Patel Robin
Published: February 2016

Resistance to carbapenems in
Enterobacteriaceae
is a clinical problem of growing significance. Difficulty in treating multidrug-resistant Gram-negative organisms with conventional antibiotics has led to a renewed and increasing use of polymyxin compounds, such as colistin. Here, we report the isolation of carbapenem- and colistin-resistant
Enterobacter cloacae
from a polymicrobial lower extremity wound in an ambulatory patient. Whole-genome sequencing demonstrated the presence of chromosomal
bla
IMI-1
and
bla
AmpC
, as well as numerous efflux pump genes.
Towards Rational Design of a Toxoid Vaccine against the Heat-Stable Toxin of Escherichia coli
Authors: Taxt Arne M. , Diaz Yuleima , Aasland Rein , Clements John D. , Nataro James P. , Sommerfelt Halvor , Puntervoll Pål
Published: February 2016

Enterotoxigenic
Escherichia coli
(ETEC) is an important cause of diarrheal disease and death in children <5 years old. ETEC strains that express the heat-stable toxin (ST), with or without the heat-labile toxin, are among the four most important diarrhea-causing pathogens. This makes ST an attractive target for an ETEC vaccine. An ST vaccine should be nontoxic and elicit an immune response that neutralizes native ST without cross-reacting with the human endogenous guanylate cyclase C receptor ligands. To identify variants of ST with no or low toxicity, we screened a library of all 361 possible single-amino-acid mutant forms of ST by using the T84 cell assay. Moreover, we identified mutant variants with intact epitopes by screening for the ability to bind neutralizing anti-ST antibodies. ST mutant forms with no or low toxicity and intact epitopes are termed toxoid candidates, and the top 30 candidates all had mutations of residues A14, N12, and L9. The identification of nontoxic variants of L9 strongly suggests that it is a novel receptor-interacting residue, in addition to the previously identified N12, P13, and A14 residues. The screens also allowed us to map the epitopes of three neutralizing monoclonal antibodies, one of which cross-reacts with the human ligand uroguanylin. The common dominant epitope residue for all non-cross-reacting antibodies was Y19. Our results suggest that it should be possible to rationally design ST toxoids that elicit neutralizing immune responses against ST with minimal risk of immunological cross-reactivity.
The Campylobacter jejuni Ferric Uptake Regulator Promotes Acid Survival and Cross-Protection against Oxidative Stress
Authors: Askoura Momen , Sarvan Sabina , Couture Jean-François , Stintzi Alain
Published: February 2016

Campylobacter jejuni
is a prevalent cause of bacterial gastroenteritis in humans worldwide. The mechanisms by which
C. jejuni
survives stomach acidity remain undefined. In the present study, we demonstrated that the
C. jejuni
ferric uptake regulator (Fur) plays an important role in
C. jejuni
acid survival and acid-induced cross-protection against oxidative stress. A
C. jejuni
Δ
fur
mutant was more sensitive to acid than the wild-type strain. Profiling of the acid stimulon of the
C. jejuni
Δ
fur
mutant allowed us to uncover Fur-regulated genes under acidic conditions. In particular, Fur was found to upregulate genes involved in flagellar and cell envelope biogenesis upon acid stress, and mutants with deletions of these genes were found to be defective in surviving acid stress. Interestingly, prior acid exposure of
C. jejuni
cross-protected against oxidative stress in a catalase (KatA)- and Fur-dependent manner. Western blotting and reverse transcription-quantitative PCR revealed increased expression of KatA upon acid stress. Electrophoretic mobility shift assays (EMSAs) demonstrated that the binding affinity between Fur and the
katA
promoter is reduced
in vitro
under conditions of low pH, rationalizing the higher levels of expression of
katA
under acidic conditions. Strikingly, the Δ
fur
mutant exhibited reduced virulence in both human epithelial cells and the
Galleria mellonella
infection model. Altogether, this is the first study showing that, in addition to its role in iron metabolism, Fur is an important regulator of
C. jejuni
acid responses and this function cross-protects against oxidative stress. Moreover, our results clearly demonstrate Fur's important role in
C. jejuni
pathogenesis.
Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot
Authors: Atkins Katherine , van Hoek Albert Jan , Watson Conall , Baguelin Marc , Choga Lethiwe , Patel Anika , Raj Thara , Jit Mark , Griffiths Ulla
Published: February 2016

Objective

To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies.

Design

We analysed 2013–2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011–2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme.

Setting

All London boroughs.

Participants

London-based GPs, and pharmacies that currently offer seasonal flu vaccination.

Interventions

Not applicable.

Main outcome measures

Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative.

Results

No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to £2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data.

Conclusions

Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data.
Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis
Authors: Whelan Kelly A , Merves Jamie F , Giroux Veronique , Tanaka Koji , Guo Andy , Chandramouleeswaran Prasanna M , Benitez Alain J , Dods Kara , Que Jianwen , Masterson Joanne C , Fernando Shahan D , Godwin Bridget C , Klein-Szanto Andres J , Chikwava Kudakwashe , Ruchelli Eduardo D , Hamilton Kathryn E , Muir Amanda B , Wang Mei-Lun , Furuta Glenn T , Falk Gary W , Spergel Jonathan M , Nakagawa Hiroshi
Published: February 2016

Objective

The influence of eosinophilic oesophagitis (EoE)-associated inflammation upon oesophageal epithelial biology remains poorly understood. We investigated the functional role of autophagy in oesophageal epithelial cells (keratinocytes) exposed to the inflammatory EoE milieu.

Design

Functional consequences of genetic or pharmacological autophagy inhibition were assessed in endoscopic oesophageal biopsies, human oesophageal keratinocytes, single cell-derived ex vivo murine oesophageal organoids as well as a murine model recapitulating EoE-like inflammation and basal cell hyperplasia. Gene expression, morphological and functional characterisation of autophagy and oxidative stress were performed by transmission electron microscopy, immunostaining, immunoblotting, live cell imaging and flow cytometry.

Results

EoE-relevant inflammatory conditions promoted autophagy and basal cell hyperplasia in three independent murine EoE models and oesophageal organoids. Inhibition of autophagic flux via chloroquine treatment augmented basal cell hyperplasia in these model systems. Oesophageal keratinocytes stimulated with EoE-relevant cytokines, including tumour necrosis factor-α and interleukin-13 exhibited activation of autophagic flux in a reactive oxygen species-dependent manner. Autophagy inhibition via chloroquine treatment or depletion of Beclin-1 or ATG-7, augmented oxidative stress induced by EoE-relevant stimuli in murine EoE, oesophageal organoids and human oesophageal keratinocytes. Oesophageal epithelia of paediatric EoE patients with active inflammation displayed increased autophagic vesicle content compared with normal and EoE remission subjects. Functional flow cytometric analysis revealed autophagic flux in human oesophageal biopsies.

Conclusions

Our findings reveal for the first time that autophagy may function as a cytoprotective mechanism to maintain epithelial redox balance and homeostasis under EoE inflammation-associated stress, providing mechanistic insights into the role of autophagy in EoE pathogenesis.
The influence of photoperiod on the reproductive physiology of the greater red musk shrew (Crociduraflavescens)
Authors: Hoole C. , McKechnie A.E. , Parker D.M. , Bennett N.C.
Published: February 2016

Photoperiodism involves the use of both absolute measures of day length and the direction in which day length is changing as a cue for regulating seasonal changes in physiology and behaviour so that birth and lactation coincide with optimal resource availability, increasing offspring survival. Induced ovulation and opportunistic breeding is often found in species that are predominantly solitary and territorial. In this study, the photoperiodic reproductive responses of male greater red musk shrews (Crocidura flavescens (I. Geoffroy Saint-Hilaire, 1827)) were investigated in the laboratory. The presence of spermatozoa regardless of the light cycle, suggest that although the shrews are photoresponsive, they may be capable of breeding throughout the year. Significantly greater testicular volume and seminiferous tubule diameter following exposure to a short day-light cycle suggests that these animals may have breeding peaks that correspond to short days. The presence of epidermal spines on the penis indicates that the shrew is likely also an induced ovulator. Flexible breeding patterns combined with induced ovulation affords this solitary species the greatest chance of reproductive success.
Buckling Analysis of Variable Thickness Radially Functionally Graded Annular Sector Plates Resting on Two-Parameter Elastic Foundations by the GDQ Method
Authors: Alinaghizadeh Farhad , Shariati Mahmoud
Published: February 2016

In this paper, buckling analysis of thick radially functionally graded circular/annular sector plates with variable thickness resting on two-parameter elastic foundations is studied. The material properties vary along radial direction according to either an exponential or a power-law distribution. The stability equations are derived using the adjacent equilibrium criterion and are based on a higher order shear deformation theory. The generalized differential quadrature method is employed to discretize the stability equations and convert them into a system of algebraic eigenvalue problem. The formulation and method of solution are validated by performing comparison studies with the available results in the open literature. Then, the effects of power-law index, boundary conditions, thickness variation and coefficients of foundation on the critical buckling load of the circular/annular sector plates subjected to different types of in-plane compressions or in-plane shear are investigated in detail.