bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapy with proton‐pump inhibitors for gastroesophageal reflux disease does not reduce the risk for severe exacerbations in COPD
Authors: Baumeler Luzia , Papakonstantinou Eleni , Milenkovic Branislava , Lacoma Alicia , Louis Renaud , Aerts Joachim G. , Welte Tobias , Kostikas Konstantinos , Blasi Francesco , Boersma Wim , Torres Antoni , Rohde Gernot G.U. , Boeck Lucas , Rakic Janko , Scherr Andreas , Tamm Michael , Stolz Daiana
Published: March 2016

Background and objective

Gastroesophageal reflux disease (GERD) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (COPD) exacerbation. We hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable COPD.

Methods

A total of 638 patients with stable COPD for ≥6 weeks, ≥10 pack‐years of smoking and Global Initiative for Chronic Obstructive Lung Disease II–IV seeking care in tertiary hospitals in eight European countries in the Predicting Outcome using Systemic Markers in Severe Exacerbations‐COPD cohort was prospectively evaluated by us. Comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. Median observation time was 24 months. The primary study outcomes were exacerbation and/or death.

Results

A total of 85 (13.3%) of COPD patients were on anti‐GERD therapy. These patients had higher annual and higher severe exacerbation rates (P = 0.009 and P = 0.002), decreased quality of life (SF‐36: activity score P = 0.004, St. George's Respiratory Questionnaire: physical functioning P = 0.013 and social functioning P = 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (P = 0.033) and Modified Medical Research Council scores (P = 0.002), shorter 6‐min walking distance (P = 0.0004) and a higher adjusted Charlson score (P < 0.0001). Anti‐GERD therapy was associated with a shorter time to severe exacerbation (HR 2.05 95% CI 1.37–3.08). Using three multivariable Cox‐regression models, this association was independent of the following: (i) adjusted Charlson score and FEV1% predicted (HR 1.91 95% CI 1.26–2.90); (ii) adjusted Charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and Modified Medical Research Council (HR 1.62 95% CI 1.04–2.54); and (iii) adjusted Charlson score, FEV1% predicted and nine classes of medication for comorbidities (HR 1.63 95% CI 1.04–2.53).

Conclusion

These findings suggest that patients with stable COPD receiving acid‐suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations.
Quantitative Risk Analysis on the Transport of Dangerous Goods Through a Bi‐Directional Road Tunnel
Authors: Caliendo Ciro , De Guglielmo Maria Luisa
Published: March 2016

A quantitative risk analysis (QRA) regarding dangerous goods vehicles (DGVs) running through road tunnels was set up. Peak hourly traffic volumes (VHP), percentage of heavy goods vehicles (HGVs), and failure of the emergency ventilation system were investigated in order to assess their impact on the risk level. The risk associated with an alternative route running completely in the open air and passing through a highly populated urban area was also evaluated. The results in terms of social risk, as F/N curves, show an increased risk level with an increase the VHP, the percentage of HGVs, and a failure of the emergency ventilation system. The risk curves of the tunnel investigated were found to lie both above and below those of the alternative route running in the open air depending on the type of dangerous goods transported. In particular, risk was found to be greater in the tunnel for two fire scenarios (no explosion). In contrast, the risk level for the exposed population was found to be greater for the alternative route in three possible accident scenarios associated with explosions and toxic releases. Therefore, one should be wary before stating that for the transport of dangerous products an itinerary running completely in the open air might be used if the latter passes through a populated area. The QRA may help decisionmakers both to implement additional safety measures and to understand whether to allow, forbid, or limit circulation of DGVs.
Outsourcing Oversight and ARRA 2009: What Factors Explain State Agencies’ Decision to Pursue Collaborative Monitoring?
Authors: Anguelov Lachezar G.
Published: March 2016

The research question raised is this study is: what factors affect state agencies' decisions to outsource oversight? The outsourcing of oversight here is conceptualized as a distinct occurrence of collaborative monitoring that expands the traditional principal–agent dyad common in the contracting literature to a small network of three agents. The adoption of the Recovery Act (ARRA) of 2009 presents a workload surge for state agencies that need to implement novel monitoring requirements in addition to their traditional practices regarding the management of grants and contracts. As an external factor creating a dynamic contracting environment the Act is hypothesized to increase the probability that state agencies outsource oversight. Additionally professional capacity is also a factor that might affect state agencies’ decision to contract out monitoring functions. Results from logistic regressions suggest that on average the factors measuring workload surge due to ARRA increase the probability a sampled agency outsources oversight by roughly 5 to 10%. Professional capacity on the other hand was not found to be a significant factor in the estimated models.
Florence Nightingale, William Farr and Competing Risks
Authors: Beyersmann Jan , Schrade Christine
Published: March 2016

Competing risks consider time to first event and type of first event. This subdiscipline of survival analysis is challenging in that multiple hazards determine the outcome probabilities. The paper demonstrates that Nightingale and Farr were aware of these connections in their co-operative work in hospital epidemiology. At the fourth International Statistical Congress (in London, 1860), they suggested forms for reporting hospital mortality that were conceptually more complete than many reported competing risks analyses today.
Institutional Amnesia: Sustainability and Peacebuilding in Croatia
Authors: Heideman Laura J.
Published: March 2016

This article studies the relationship between sustainability and institutional memory in postwar Croatia. Is institutional memory preserved after interventions end? Is so, how and by whom? What are the causes of loss of institutional memory? What are the consequences for sustainability and accountability? When international organizations pulled out of peacebuilding operations in Croatia in the mid to late 2000s, they quickly lost their institutional memory of their projects. Donors, international nongovernmental organizations, and intergovernmental organizations all lost their ability to recall the work they had done in the past. Using interview, ethnographic data, and archival documents gathered over five years (2008–2013), I define three types of memory—archival, human, and electronic—and show how each of these forms of memory eroded as international projects in Croatia ended. The loss of international memory has implications for international organizations' own stated goals of sustainability and their ability to achieve and assess sustainability, and for the downward accountability of donors to their beneficiaries and the countries they worked in.
Detection of HLA‐DRB1*04:207, a novel HLA‐DRB1*04 variant, in a Taiwanese hematopoietic stem cell donor
Authors: Yang K. L. , Hung J. H. , Chen C. P. , Lin P. Y.
Published: March 2016

Recombination may result in the formation of HLA‐DRB1*04:207.
How Officers Create Guardianship: An Agent‐based Model of Policing
Authors: Wise Sarah C. , Cheng Tao
Published: March 2016

Crime is a complex phenomenon, emerging from the interactions of offenders, victims, and their environment, and in particular from the presence or absence of capable guardians. Researchers have historically struggled to understand how police officers create guardianship. This presents a challenge because, in order to understand how to advise the police, researchers must have an understanding of how the current system works. The work presents an agent‐based model that simulates the movement of police vehicles, using a record of real calls for service and real levels of police staffing in spatially explicit environments to emulate the demands on the police force. The GPS traces of the simulated officers are compared with real officer movement GPS data in order to assess the quality of the generated movement patterns. The model represents an improvement on existing standards of police simulation, and points the way toward more nuanced understandings of how police officers influence the criminological environment.
A Spatial Conditioned Latin Hypercube Sampling Method for Mapping Using Ancillary Data
Authors: Gao Bingbo , Pan Yuchun , Chen Ziyue , Wu Fang , Ren Xuhong , Hu Maogui
Published: March 2016

For obtaining maps of good precision by the spatial inference method, the distribution of sampling sites in geographical and feature space is very important. For a regional variable with trends, the predicting error comes from trend estimation, variogram estimation and spatial interpolation. Based on the cLHS (conditioned Latin hypercube Sampling) method, a sampling method called scLHS (spatial cLHS) considering all these three aspects with the help of ancillary data is proposed in this article. Its advantage lies in simultaneously improving trend estimation, variogram estimation and spatial interpolation. MODIS data and simulated data were used as sampling fields to draw sample sets using scLHS, cLHS, cLHS with x and y coordinates as covariates, simple random and spatial even sampling methods, and the distribution and prediction errors of sample sets from different methods were evaluated. The results showed that scLHS performed well in balancing spreading in geographic and feature space, and can generate points pairs with small distances, and the sample sets drawn by scLHS produced smaller mapping error, especially when there were trends in the target variable.
Transfusion in children: epidemiology and 10‐year survival of transfusion recipients
Authors: Morley S. L. , Hudson C. L. , Llewelyn C. A. , Wells A. W. , Johnson A. L. , Williamson L. M. ,   for the EASTR study group
Published: March 2016

Objective

To describe the epidemiology of blood transfusion in children: including the incidence of transfusion, the diagnoses leading to transfusion, donor exposure (DE) and post‐transfusion survival.

Study design and methods

The Epidemiology and Survival of Transfusion Recipients (EASTR) Study was a multi‐centre epidemiological study with prospective survival monitoring. Cross‐sectional sampling of adult and paediatric transfusion recipients in 29 hospitals was used to select three separate cohorts of red cell (RBC), platelet (PLT) and fresh frozen plasma (FFP) recipients between October 2001 and September 2002. This paper presents the analysis of results for children <16 years.

Results

Children <16 years comprised 449 (5%) of the RBC, 362 (9%) of the FFP and 452 (13%) of the PLT recipients. In children 54% of RBC, 63% FFP and 45% PLT recipients were under 1 year of age and 57% RBC, 60% FFP and 52% PLT were male. Median (IQR) DEduring the study year was 3(2–8); 5(2–13) and 11(6–21) in the RBC, FFP and PLT cohorts, respectively. A total of 20% of RBC, 31% of FFP and 54% of PLT recipients had been exposed to >10 donors.

Perinatal conditions were the commonest indication for transfusion in the RBC (36%) and FFP (44%) cohorts and comprised 31% of the PLT cohort. Medical conditions (48%), predominantly malignancy (33%), were the most frequent indication in the PLT cohort. The 10 year (95% CI) survival rates were 81% (77–85%), 72% (67–76%) and 71% (66–75%)for RBC, FFP and PLT cohorts, respectively.

Conclusions

Around half of paediatric transfusion recipients are under 1 year of age. Exposure to components from multiple donors is common. At least 70% of paediatric recipients are long survivors and are at risk for late complications of transfusion.
Characterisation of clinical Staphylococcus aureus isolates harbouring mecA or Panton–Valentine leukocidin genes from four tertiary care hospitals in Indonesia
Authors: Santosaningsih Dewi , Santoso Sanarto , Budayanti Nyoman S. , Suata Ketut , Lestari Endang S. , Wahjono Hendro , Djamal Aziz , Kuntaman Kuntaman , van Belkum Alex , Laurens Mitchell , Snijders Susan V. , Willemse‐Erix Diana , Goessens Wil H. , Verbrugh Henri A. , Severin Juliëtte A.
Published: March 2016

Objectives

To determine the prevalence, antimicrobial susceptibility profiles and clonal distribution of either methicillin‐resistant Staphylococcus aureus (MRSA) or Panton–Valentine leukocidin (PVL)‐positive S. aureus obtained from clinical cultures in Indonesian hospitals.

Methods

S. aureus isolates from clinical cultures of patients in four tertiary care hospitals in Denpasar, Malang, Padang and Semarang were included. We assessed the antimicrobial susceptibility profiles using the Vitek2® system, determined the presence of the mecA gene and genes encoding PVL using PCR and analysed the clonal relatedness with Raman spectroscopy. SCCmec typing was performed for all MRSA isolates. Multilocus sequence typing (MLST) was performed for a subset of isolates.

Results

In total, 259 S. aureus strains were collected. Of these, 17/259 (6.6%) and 48/259 (18.5%) were MRSA and PVL‐positive methicillin‐susceptible S. aureus (MSSA), respectively. The prevalence of MRSA and PVL‐positive MSSA ranged between 2.5–8.9% and 9.5–29.1%, respectively and depended on geographic origin. PVL‐positive MRSA were not detected. Raman spectroscopy of the strains revealed multiple Raman types with two predominant clusters. We also showed possible transmission of a ST239‐MRSA‐SCCmec type III strain and a ST121 PVL‐positive MSSA in one of the hospitals.

Conclusions

We showed that MRSA and PVL‐positive MSSA are of clinical importance in Indonesian hospitals. A national surveillance system should be set‐up to further monitor this. To reduce the prevalence of MRSA in Indonesian hospitals, a bundle of intervention measures is highly recommended.
AABB Committee Report: reducing transfusion‐transmitted cytomegalovirus infections
Authors:   AABB, Clinical Transfusion Medicine Committee, Heddle Nancy M. , Boeckh Michael , Grossman Brenda , Jacobson Jessica , Kleinman Steven , Tobian Aaron A.R. , Webert Kathryn , Wong Edward C.C. , Roback John D.
Published: March 2016

Transfusion‐transmitted cytomegalovirus (TT‐CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life‐threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT‐CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV‐serology and leukoreduction to prevent TT‐CMV for at‐risk patients. Other approaches may also be feasible to prevent TT‐CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large‐scale clinical trials will be performed to determine whether leukoreduction, CMV‐serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV‐safe blood components.
Hypoglycemia associated with refeeding syndrome in a cat
Authors: DeAvilla Marisa D. , Leech Elizabeth B.
Published: March 2016

Objective

To describe the clinical presentation and biochemical abnormalities occurring during the successful treatment of refeeding syndrome in a cat.

Case Summary

A 2‐year‐old neutered male domestic shorthair cat presented after having been missing for 12 weeks. The cat had clinical signs of severe starvation. Common complications developed during refeeding (eg, hypophosphatemia, hypokalemia, and hemolytic anemia). The cat also developed hypoglycemia, a complication common in people but not previously reported in a cat. Hypoglycemia and electrolyte deficiencies were managed with intravenous supplementation. The cat was successfully treated and was discharged alive 7 days after presentation.

New or Unique Information Provided

Hypoglycemia has not been reported previously as a complication of refeeding in a cat. Frequent monitoring of electrolyte, mineral, and blood glucose concentrations is essential to successful management of refeeding syndrome. The ideal refeeding strategy is unknown at this time. Evidence suggests that a diet low in carbohydrate decreases the likelihood of metabolic derangements commonly associated with refeeding.
Frequency of Penetration of the Digital Flexor Tendon Sheath and Distal Interphalangeal Joint Using a Direct Endoscopic Approach to the Navicular Bursa in Horses
Authors: Kane‐Smyth Justine , Taylor Sarah Elizabeth , García Eugenio Cillán , Reardon Richard J.M.
Published: March 2016

Objective

To evaluate the frequency of inadvertent penetration of the digital flexor tendon sheath (DFTS) and/or distal interphalangeal joint (DIPJ) when using a direct endoscopic approach to the navicular bursa, and to evaluate an alternate direct approach to the navicular bursa.

Study Design

Cadaveric study.

Sample Population

Equine cadaver limbs (n = 40 for direct; n = 12 for alternate approach).

Methods

Four surgeons performed the direct endoscopic approach to the navicular bursa on 10 limbs each. Frequencies of inadvertent synovial penetration and iatrogenic damage were compared between surgeons. Use of an alternate direct approach, adopting a straight parasagittal trajectory, was evaluated by 2 surgeons.

Results

Inadvertent synovial penetration occurred in 45% of limbs (DFTS 37.5%; DIPJ 17.5%; and both structures 10%). Successful bursa entry was achieved on the first attempt in 45% of limbs. Significant variation in frequency of inadvertent synovial penetration was observed between surgeons (range 10–80%). Inadvertent synovial penetration did not occur when using the alternate direct technique. Iatrogenic damage to navicular bone fibrocartilage and/or deep digital flexor tendon occurred in 55% of limbs using the direct endoscopic approach and in 0% of limbs using the alternate direct approach.

Conclusion

Because of the considerable risk of inadvertent penetration of the DFTS and/or the DIPJ when making a direct endoscopic approach to the navicular bursa, it is advisable to investigate for inadvertent penetration when treating navicular bursa sepsis using a direct approach. The alternate direct technique may reduce the risk of inadvertent penetration; however, the view within the bursa may be restricted.
Metalloproteinase production from macrophages – a perfect storm leading to atherosclerotic plaque rupture and myocardial infarction
Authors: Newby Andrew C.
Published: March 2016

New Findings

What is the topic of this review?

The review discusses how in atherosclerotic plaques, a combination of inflammatory mediators together with loss of anti inflammatory factors is most likely to be responsible for the excess of MMP over TIMP expression that causes plaque rupture and myocardial infarction.

What advances does it highlight?

Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) is divergent between human and mouse macrophages. There is prostaglandin E2‐dependent and ‐independent regulation. Inflammatory cytokines act through distinct (albeit overlapping) signalling pathways to elicit different patterns of MMP and TIMP expression. Transcriptional and epigenetic regulation occurs.

Matrix metalloproteinases (MMPs) produced from macrophages contribute to plaque rupture, atherothrombosis and myocardial infarction. New treatments could emerge from defining the mediators and underlying mechanisms. In human monocytes, prostaglandin E2 (PGE2) stimulates MMP production, and inflammatory mediators such as tumour necrosis factor α, interleukin‐1 and Toll‐like receptor ligands can act either through or independently of PGE2. Differentiation of human monocytes to non‐foamy macrophages increases constitutive expression of MMP‐7, ‐8, ‐9, ‐14 and ‐19 and tissue inhibitor of MMP (TIMP)‐1 to ‐3 through unknown, PGE2‐independent mechanisms. Human macrophages express more MMP‐1, ‐7 and ‐9 and TIMP‐3 and less MMP‐12 and ‐13 than mouse macrophages. Inflammatory mediators working through activator protein‐1 and nuclear factor‐κB transcription factor pathways upregulate MMP‐1, ‐3, ‐10, ‐12 and ‐14 in human macrophages (MMP‐9, ‐12 and ‐13 in mice), and studies with plaque tissue sections and isolated foam cells confirm this conclusion in vivo. Classical activation with granulocyte–macrophage colony‐stimulating factor upregulates MMP‐12, whereas interferon‐γ upregulates MMP‐12, ‐14 and ‐25 and downregulates TIMP‐3 in human but not mouse macrophages. Alternative activation with interleukin‐4 markedly stimulates the expression of only MMP‐12 in humans and MMP‐19 in mice. The anti‐inflammatory cytokines interleukin‐10 and transforming growth factor‐β decrease production of several MMPs. Epigenetic upregulation of MMP‐14 during foam cell formation or by granulocyte–macrophage colony‐stimulating factor occurs by decreasing miRNA‐24. A ‘perfect storm’ caused by a combination of these mechanisms is most likely to promote MMP‐mediated macrophage invasion, tissue destruction and atherosclerotic plaque rupture.
Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?
Authors: Stephens G. J.
Published: March 2016

Cerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and typically associated with deficiency in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent. The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid receptors, predominantly the cannabinoid CB1 receptor (CB1R) in the cerebellum; activation of this system in the cerebellar cortex is associated with deficits in motor coordination characteristic of ataxia, effects which can be prevented by CB1R antagonists. Of further interest are various findings that CB1R deficits may also induce a progressive ataxic phenotype. Together these studies suggest that motor coordination is reliant on maintaining the correct balance in eCB system signalling. Recent work also demonstrates deficient cannabinoid signalling in the mouse ‘ducky2J’ model of ataxia. In light of these points, the potential mechanisms whereby cannabinoids may modulate the eCB system to ameliorate dysfunction associated with cerebellar ataxias are considered.

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Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations
Authors: Cheong Jean N. , Wlodek Mary E. , Moritz Karen M. , Cuffe James S. M.
Published: March 2016

Babies born small are at an increased risk of developing myriad adult diseases. While growth restriction increases disease risk in all individuals, often a second hit is required to unmask ‘programmed’ impairments in physiology. Programmed disease outcomes are demonstrated more commonly in male offspring compared with females, with these sex‐specific outcomes partly attributed to different placenta‐regulated growth strategies of the male and female fetus. Pregnancy is known to be a major risk factor for unmasking a number of conditions and can be considered a ‘second hit’ for women who were born small. As such, female offspring often develop impairments of physiology for the first time during pregnancy that present as pregnancy complications. Numerous maternal stressors can further increase the risk of developing a maternal complication during pregnancy. Importantly, these maternal complications can have long‐term consequences for both the mother after pregnancy and the developing fetus. Conditions such as preeclampsia, gestational diabetes and hypertension as well as thyroid, liver and kidney diseases are all conditions that can complicate pregnancy and have long‐term consequences for maternal and offspring health. Babies born to mothers who develop these conditions are often at a greater risk of developing disease in adulthood. This has implications as a mechanism for transmission of disease across generations. In this review, we discuss the evidence surrounding long‐term intergenerational implications of being born small and/or experiencing stress during pregnancy on programming outcomes.

image
A quantitative metrology for performance characterization of five breast tomosynthesis systems based on an anthropomorphic phantom
Authors: Ikejimba Lynda , Lo Joseph Y. , Chen Yicheng , Oberhofer Nadia , Kiarashi Nooshin , Samei Ehsan
Published: March 2016

Purpose:

In medical imaging systems, proper rendition of anatomy is essential in discerning normal tissue from disease. Currently, digital breast tomosynthesis (DBT) systems are evaluated using subjective evaluation of lesion visibility in uniform phantoms. This study involved the development of a new methodology to objectively measure the rendition of a 3D breast model by an anthropomorphic breast phantom, and its implementation on five clinical DBT systems of different makes and models.

Methods:

A 3D, patient‐based breast phantom was fabricated based on XCAT breast models. This phantom was imaged on representative breast tomosynthesis systems. The ability of tomosynthesis systems to accurately reproduce the 3D structure of the breast was assessed by computational analysis of the resultant images in terms of three groups of indices: contrast index (CI), reflective of local difference between adipose and glandular material; adipose variability index (AVI), reflective of contributions of noise and artifacts within uniform adipose regions; and contrast detectability, which describes contrast against local background variability and is described by contrast variability index (CVI), coefficient of variation (COV), contrast to adipose variability index (CAVI), and contrast to noise ratio index (CNRI). The indices were obtained by comparing the image data to the gold standard 3D distribution of breast tissue in the model. Corresponding indices were measured within variable region of interest (ROI) sizes ranging from 10 to 37 mm. The characterization was performed on five tomosynthesis systems: Fuji Aspire Crystal, GE Essential, Hologic Dimension, IMS Giotto, and Siemens Inspiration, all evaluated at a fixed dose of 1.5 mGy average glandular dose, anonymized in random order from A to E.

Results:

Results are provided as a function of ROI size. The systems ranked orders in terms of CI with values of 7.4%, 7.0%, 6.9%, 6.4%, and 5.2% for systems A–E, respectively. This system ranking was identical for CNRI. Both CI and CNRI were constant over ROI size. The ranking was similar for CVI. The COV also changed little with ROI size and was similar across systems. For 10 mm ROIs, the average system COV was 0.7, which reduced to 0.5 with 37 mm ROIs. Two systems (A and B) exhibited highest AVI values when measured in 10 mm ROIs. This, however, was ROI‐size‐dependent with the three other systems (C–E) yielding higher AVI values when measured with 37 mm ROIs. Two systems (B and E) showed inferior CAVI compared to others.

Conclusions:

The quality of rendition tracked with differences in image appearance across systems. The findings illustrate that the anthropomorphic phantom can be used as a basis to extract quantitative values of image attributes in DBT.
Design and characterization of a new high‐dose‐rate brachytherapy Valencia applicator for larger skin lesions
Authors: Candela‐Juan C. , Niatsetski Y. , van der Laarse R. , Granero D. , Ballester F. , Perez‐Calatayud J. , Vijande J.
Published: March 2016

Purpose:

The aims of this study were (i) to design a new high‐dose‐rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron‐HDR or Flexitron afterloader (Elekta Brachytherapy) with a 192Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water.

Methods:

The penelope2008 MC code was used to optimize dwell positions and dwell times. Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a 192Ir mHDR‐v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel‐plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber.

Results:

The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off‐axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%.

Conclusions:

The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.
Auditory evoked potentials in the auditory system of a beluga whale Delphinapterus leucas to prolonged sound stimuli
Authors: Popov Vladimir V. , Sysueva Evgenia V. , Nechaev Dmitry I. , Rozhnov Vyatcheslav V. , Supin Alexander Ya.
Published: March 2016

The effects of prolonged (up to 1500 s) sound stimuli (tone pip trains) on evoked potentials (the rate following response, RFR) were investigated in a beluga whale. The stimuli (rhythmic tone pips) were of frequencies of 45, 64, and 90 kHz at levels from 20 to 60 dB above threshold. Two experimental protocols were used: short- and long-duration. For the short-duration protocol, the stimuli were 500-ms-long pip trains that repeated at a rate of 0.4 trains/s. For the long-duration protocol, the stimuli were continuous pip successions lasting up to 1500 s. The RFR amplitude gradually decreased by three to seven times from 10 ms to 1500 s of stimulation. Decrease of response amplitude during stimulation was approximately proportional to initial (at the start of stimulation) response amplitude. Therefore, even for low stimulus level (down to 20 dB above the baseline threshold) the response was never suppressed completely. The RFR amplitude decay that occurred during stimulation could be satisfactorily approximated by a combination of two exponents with time constants of 30−80 ms and 3.1−17.6 s. The role of adaptation in the described effects and the impact of noise on the acoustic orientation of odontocetes are discussed.
A case for historic joint rupture of the San Andreas and San Jacinto faults
Authors: Lozos Julian C.
Published: March 2016

The San Andreas and San Jacinto faults likely slipped together in a single earthquake in 1812 and are capable of doing so again.
Experimental test of Landauer’s principle in single-bit operations on nanomagnetic memory bits
Authors: Hong Jeongmin , Lambson Brian , Dhuey Scott , Bokor Jeffrey
Published: March 2016

The minimum energy dissipated in switching a magnetic bit measured to be consistent with the Landauer limit of
k
B
T
ln(2).
Single-plasmon interferences
Authors: Dheur Marie-Christine , Devaux Eloïse , Ebbesen Thomas W. , Baron Alexandre , Rodier Jean-Claude , Hugonin Jean-Paul , Lalanne Philippe , Greffet Jean-Jacques , Messin Gaétan , Marquier François
Published: March 2016

The wave-particle duality of single surface plasmons is demonstrated using a plasmonic beam splitter on a flat gold device.
Low-temperature plasticity of olivine revisited with in situ TEM nanomechanical testing
Authors: Idrissi Hosni , Bollinger Caroline , Boioli Francesca , Schryvers Dominique , Cordier Patrick
Published: March 2016

The flow properties of the mineral olivine under lithospheric conditions, as seen in the transmission electron microscope (TEM).
Sclerostin: More than a bone formation brake
Authors: Rauch Frank , Adachi Rick
Published: March 2016

Anti-sclerostin spurs an unexpected acceleration of bone erosion in a mouse model of rheumatoid arthritis (Wehmeyer
et al
., this issue).
Diverse effects of statins in Alzheimer’s disease
Authors: Janson Christopher G.
Published: March 2016

Statins are linked to β-amyloid peptide through an astrocyte-mediated pathway.
Soybean Ferritin Expression in Saccharomyces cerevisiae Modulates Iron Accumulation and Resistance to Elevated Iron Concentrations
Authors: de Llanos Rosa , Martínez-Garay Carlos Andrés , Fita-Torró Josep , Romero Antonia María , Martínez-Pastor María Teresa , Puig Sergi
Published: March 2016

Fungi, including the yeast
Saccharomyces cerevisiae
, lack ferritin and use vacuoles as iron storage organelles. This work explored how plant ferritin expression influenced baker's yeast iron metabolism. Soybean seed ferritin H1 (SFerH1) and SFerH2 genes were cloned and expressed in yeast cells. Both soybean ferritins assembled as multimeric complexes, which bound yeast intracellular iron
in vivo
and, consequently, induced the activation of the genes expressed during iron scarcity. Soybean ferritin protected yeast cells that lacked the Ccc1 vacuolar iron detoxification transporter from toxic iron levels by reducing cellular oxidation, thus allowing growth at high iron concentrations. Interestingly, when simultaneously expressed in
ccc1
Δ cells, SFerH1 and SFerH2 assembled as heteropolymers, which further increased iron resistance and reduced the oxidative stress produced by excess iron compared to ferritin homopolymer complexes. Finally, soybean ferritin expression led to increased iron accumulation in both wild-type and
ccc1
Δ yeast cells at certain environmental iron concentrations.

IMPORTANCE
Iron deficiency is a worldwide nutritional disorder to which women and children are especially vulnerable. A common strategy to combat iron deficiency consists of dietary supplementation with inorganic iron salts, whose bioavailability is very low. Iron-enriched yeasts and cereals are alternative strategies to diminish iron deficiency. Animals and plants possess large ferritin complexes that accumulate, detoxify, or buffer excess cellular iron. However, the yeast
Saccharomyces cerevisiae
lacks ferritin and uses vacuoles as iron storage organelles. Here, we explored how soybean ferritin expression influenced yeast iron metabolism, confirming that yeasts that express soybean seed ferritin could be explored as a novel strategy to increase dietary iron absorption.
Biofilms on Hospital Shower Hoses: Characterization and Implications for Nosocomial Infections
Authors: Soto-Giron Maria J. , Rodriguez-R Luis M. , Luo Chengwei , Elk Michael , Ryu Hodon , Hoelle Jill , Santo Domingo Jorge W. , Konstantinidis Konstantinos T.
Published: March 2016

Although the source of drinking water (DW) used in hospitals is commonly disinfected, biofilms forming on water pipelines are a refuge for bacteria, including possible pathogens that survive different disinfection strategies. These biofilm communities are only beginning to be explored by culture-independent techniques that circumvent the limitations of conventional monitoring efforts. Hence, theories regarding the frequency of opportunistic pathogens in DW biofilms and how biofilm members withstand high doses of disinfectants and/or chlorine residuals in the water supply remain speculative. The aim of this study was to characterize the composition of microbial communities growing on five hospital shower hoses using both 16S rRNA gene sequencing of bacterial isolates and whole-genome shotgun metagenome sequencing. The resulting data revealed aMycobacterium-like population, closely related toMycobacterium rhodesiaeandMycobacterium tusciae, to be the predominant taxon in all five samples, and its nearly complete draft genome sequence was recovered. In contrast, the fraction recovered by culture was mostly affiliated withProteobacteria, including members of the generaSphingomonas,Blastomonas, andPorphyrobacter.The biofilm community harbored genes related to disinfectant tolerance (2.34% of the total annotated proteins) and a lower abundance of virulence determinants related to colonization and evasion of the host immune system. Additionally, genes potentially conferring resistance to β-lactam, aminoglycoside, amphenicol, and quinolone antibiotics were detected. Collectively, our results underscore the need to understand the microbiome of DW biofilms using metagenomic approaches. This information might lead to more robust management practices that minimize the risks associated with exposure to opportunistic pathogens in hospitals.
Kinetics of Inactivation of Bacillus subtilis subsp.
niger
Spores and Staphylococcus albus on Paper by Chlorine Dioxide Gas in an Enclosed Space
Authors: Wang Tao , Wu Jinhui , Qi Jiancheng , Hao Limei , Yi Ying , Zhang Zongxing
Published: March 2016

Bacillus subtilis
subsp.
niger
spore and
Staphylococcus albus
are typical biological indicators for the inactivation of airborne pathogens. The present study characterized and compared the behaviors of
B. subtilis
subsp.
niger
spores and
S. albus
in regard to inactivation by chlorine dioxide (ClO
2
) gas under different gas concentrations and relative humidity (RH) conditions. The inactivation kinetics under different ClO
2
gas concentrations (1 to 5 mg/liter) were determined by first-order and Weibull models. A new model (the Weibull-H model) was established to reveal the inactivation tendency and kinetics for ClO
2
gas under different RH conditions (30 to 90%). The results showed that both the gas concentration and RH were significantly (
P
< 0.05) and positively correlated with the inactivation of the two chosen indicators. There was a rapid improvement in the inactivation efficiency under high RH (>70%). Compared with the first-order model, the Weibull and Weibull-H models demonstrated a better fit for the experimental data, indicating nonlinear inactivation behaviors of the vegetative bacteria and spores following exposure to ClO
2
gas. The times to achieve a six-log reduction of
B. subtilis
subsp.
niger
spore and
S. albus
were calculated based on the established models. Clarifying the kinetics of inactivation of
B. subtilis
subsp.
niger
spores and
S. albus
by ClO
2
gas will allow the development of ClO
2
gas treatments that provide an effective disinfection method.

IMPORTANCE
Chlorine dioxide (ClO
2
) gas is a novel and effective fumigation agent with strong oxidization ability and a broad biocidal spectrum. The antimicrobial efficacy of ClO
2
gas has been evaluated in many previous studies. However, there are presently no published models that can be used to describe the kinetics of inactivation of airborne pathogens by ClO
2
gas under different gas concentrations and RH conditions. The first-order and Weibull (Weibull-H) models established in this study can characterize and compare the behaviors of
Bacillus subtilis
subsp.
niger
spores and
Staphylococcus
albus
in regard to inactivation by ClO
2
gas, determine the kinetics of inactivation of two chosen strains under different conditions of gas concentration and RH, and provide the calculated time to achieve a six-log reduction. These results will be useful to determine effective conditions for ClO
2
gas to inactivate airborne pathogens in contaminated air and other environments and thus prevent outbreaks of airborne illness.
Effectiveness of footwear and foot orthoses for calcaneal apophysitis: a 12-month factorial randomised trial
Authors: James Alicia M , Williams Cylie M , Haines Terry P
Published: March 2016

Objective

Calcaneal apophysitis, is a relatively common cause of heel pain in children. Very few randomised studies have evaluated treatment options. This trial compared the effectiveness of currently employed treatment options for the relief of pain and disability associated with calcaneal apophysitis.

Design

Factorial 2×2 randomised comparative effectiveness trial with 1, 2, 6 and 12-month follow-up.

Setting

Participants were recruited from the caseload of podiatrists at Monash health and Peninsula Health.

Participants

Children aged 8–14 years with clinically diagnosed calcaneal apophysitis.

Interventions

Treatment factor 1: two different types of in-shoe orthoses: a heel raise or prefabricated orthoses. Treatment factor 2: footwear replacement or no footwear replacement.

Outcomes

Our primary outcome was functional disability, the secondary outcomes were pain and ankle dorsiflexion range.

Results

A total of 133 children and their parents responded to the recruitment advertisement, 124 participated in the trial.

At the 1 and 2-month follow-up points, there was a main effect of the shoe insert (heel raise) in only the physical domain for the Oxford ankle foot questionnaire (p=0.04). At the 6 and 12-month follow-up points, there was no main effect or interaction effect for any outcome measure.

Conclusion

This trial indicates at the 2-month time point there is a relative advantage in the use of heel raises over prefabricated orthoses for the treatment for calcaneal apophysitis. At 12 months there was no relative advantage to any one of the investigated treatment choices over another. Therefore, if a physical impact is experienced for greater than 2 months, the selection of treatment choice may defer to clinical judgement, cost-minimisation and or patient preference.

Trial registration number

ACTRN12609000696291.
Distribution of lifespan gain from primary prevention intervention
Authors: Finegold Judith A , Shun-Shin Matthew J , Cole Graham D , Zaman Saman , Maznyczka Annette , Zaman Sameer , Al-Lamee Rasha , Ye Siqin , Francis Darrel P
Published: March 2016

Objective

When advising patients about possible initiation of primary prevention treatment, clinicians currently do not have information on expected impact on lifespan, nor how much this increment differs between individuals.

Methods

First, UK cardiovascular and non-cardiovascular mortality data were used to calculate the mean lifespan gain from an intervention (such as a statin) that reduces cardiovascular mortality by 30%. Second, a new method was developed to calculate the probabilitydistributionof lifespan gain. Third, we performed a survey in three UK cities on 11 days between May–June 2014 involving 396 participants (mean age 40 years, 55% male) to assess how individuals evaluate potential benefit from primary prevention therapies.

Results

Among numerous identical patients, the lifespan gain, from an intervention that reduces cardiovascular mortality by 30%, is concentrated within an unpredictable minority. For example, men aged 50 years with national average cardiovascular risk have mean lifespan gain of 7 months. However, 93% of these identical individuals gain no lifespan, while the remaining 7% gain a mean of 99 months. Many survey respondents preferred achanceof large lifespan gain to the equivalent life expectancy gain given as certainty. Indeed, 33% preferred a 2% probability of 10 years to fivefold more gain, expressed as certainty of 1 year.

Conclusions

People who gain lifespan from preventative therapy gain far more than the average for their risk stratum, even if perfectly defined. This may be important in patient decision-making. Looking beyond mortality reduction alone from preventative therapy, the benefits are likely to be even larger.
Therapeutic and diagnostic outcomes of a standardised, comprehensive care pathway for patients with systemic sclerosis
Authors: Meijs Jessica , Schouffoer Anne A , Ajmone Marsan Nina , Kroft Lucia J M , Stijnen Theo , Ninaber Maarten K , Huizinga Tom W J , Vliet Vlieland Theodora P M , de Vries-Bouwstra Jeska K
Published: March 2016

Objectives

To determine the outcomes, including number of medical interventions and initiation of immunosuppressive treatment of a standardised, comprehensive, diagnostic care pathway for patients with systemic sclerosis (SSc). Patient characteristics associated with need for medical interventions and with need for immunosuppressive treatment were determined.

Methods

Data were routinely gathered in connection with a 2-day care pathway combining multidisciplinary care and complete diagnostic work-up of organ involvement in SSc. The number of patients in whom the pathway resulted in medical interventions, and/or initiation of immunosuppressives was recorded. Patient characteristics and diagnostic tests results were compared between patients with and without medical interventions, and patients with and without initiation of immunosuppressives by means of multivariable logistic regression analyses.

Results

During a period of 44 months, 226 patients with SSc were referred to the care pathway. They included 186 (82%) women with mean age of 54 (SD 14.5) years, and median disease duration of 4 years (range 1–11); 73 (32%) of them had diffuse cutaneous SSc. Medical interventions were initiated in 191 (85%) patients, including initiation of immunosuppressive treatment in n=49 (22%). Presence of telangiectasias and higher erythrocyte sedimentation rate were associated with any medical intervention. Of commonly available variables, lower age, higher skin score and absence of anticentromere antibody were associated with initiation of immunosuppressives.

Conclusions

A standardised comprehensive 2-day care pathway for patients with SSc resulted in additional diagnostic or therapeutic interventions in 85% of the patients, regardless of SSc subtype and disease duration. In 22% of the patients, immunosuppressive treatment was initiated.