bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caring for acutely unwell older residents in residential aged‐care facilities: Perspectives of staff and general practitioners
Authors: Stokoe Amy , Hullick Carolyn , Higgins Isabel , Hewitt Jacqueline , Armitage Deborah , O'Dea Ian 
Published: June 2015

AimTo explore the challenges and facilitators of managing acutely unwell residents in their residential aged‐care facilities (RACF) and transferring RACF residents to the emergency department of a tertiary referral hospital in Australia.MethodsThis exploratory study used a qualitative descriptive approach incorporating structured focus group interviews with nursing staff from RACFs and General Practitioners (GPs) within the local area. Four focus groups were held with staff from RACFs and one with GPs who visited one or more of the facilities during 2010. The interview data were analysed for themes relating to the study aims.ResultsFindings revealed both challenges and facilitators associated with managing acutely unwell older people including, communication, nursing staffing mix and numbers, use of advanced care directives, responsibilities of GPs and awareness of community services.ConclusionFrom these findings it is possible to make recommendations for alternative ways of practising and/or new models of care.
Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark: comparison with the general population
Authors: Thorsteinsson K , Ladelund S , Jensen‐Fangel S , Katzenstein TL , Johansen I Somuncu , Pedersen G , Junge J , Helleberg M , Storgaard M , Obel N , Lebech A‐M 
Published: June 2015

ObjectivesWomen living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). A recent publication found that WLWH in Denmark attend the national ICC screening programme less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH in Denmark compared with that in women in the general population.MethodsWe studied a nationwide cohort of WLWH and a cohort of 15 age‐matched women per WLWH from the general population for the period 1999–2010. Pathology samples were obtained from The Danish Pathology Data Bank, which contains nationwide records of all pathology specimens. The cumulative incidence and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology result to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN/ICC in the interpretation of results.ResultsWe followed 1140 WLWH and 17 046 controls with no prior history of ICC or hysterectomy for 9491 and 156 865 person‐years, respectively. Compared with controls, the overall incidences of CIN1 or worse (CIN1+), CIN2+ and CIN3+, but not ICC, were higher in WLWH and predicted by young age and a CD4 count < 200 cells/μL. In women with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, when we compared subgroups of WLWH and controls where women in both groups were adherent to the national ICC screening programme and had a normal baseline cytology, incidences of CIN and ICC were comparable.ConclusionsOverall, WLWH developed more cervical disease than controls. Yet, in WLWH and controls adherent to the national ICC screening programme and with normal baseline cytology, incidences of CIN and ICC were comparable.
Factors associated with transmission of influenza‐like illness in a cohort of households containing multiple children
Authors: Brown Chelsea R. , McCaw James M. , Fairmaid Emily J. , Brown Lorena E. , Leder Karin , Sinclair Martha , McVernon Jodie 
Published: June 2015

BackgroundHousehold studies of influenza‐like illness (ILI) afford opportunities to study determinants of respiratory virus transmission.ObjectivesWe examined predictors of ILI transmission within households containing at least two children.MethodsA prospective cohort study recorded ILI symptoms daily for 2712 adult and child participants during the 1998 influenza season in Victoria, Australia. Logistic and Poisson regressions were used to explore predictors of household transmission of ILI and the secondary household attack proportion (SHAP). A date of illness onset during the influenza season was used as a proxy indicator of ILI associated with influenza infection (as opposed to other aetiological causes).ResultsA total of 1009 ILI episodes were reported by 781 of 2712 (29%) participants residing in 157 households. Transmission, defined as detection of ILI in one or more household members following identification of an index case, was observed in 206 of 705 (29%) household introductions. Transmission of ILI was significantly associated with the onset of ILI in the index case during the peak influenza season compared with the remainder of the observation period (37% versus 27%, odds ratio = 1·59, 95% CI 1·09, 2·31, P = 0·017). The SHAP was 0·12, higher if the index case was of secondary school age [incidence risk ratio (IRR) = 1·80, 95% CI 1·08, 2·98, P = 0·022].ConclusionsRisk of household transmission of ILI was increased during the peak influenza season, indicating an increased burden of disease during the period of influenza circulation. In this cohort, secondary‐school‐aged children and adults were important transmitters of ILI.
Tap water versus sterile saline solution in the colonisation of skin wounds
Authors: Resende Margarida MC , Rocha Cleber A , Corrêa Nely FM , Veiga Renato RG , Passos Sandro JF , Novo Neil F , Juliano Yara , Damasceno Carlos AV 
Published: June 2015

AbstractIrrigating wounds with tap water does not increase colonisation, but controlled studies are required for further evidence. Microbial colonisation was assessed in skin wounds, before and after irrigation with tap water, and was compared with irrigation using 0·9% sodium chloride sterile solution. The study included 120 subjects with chronic, traumatic, vascular, pressure or neuropathic wounds. A total of 60 wounds were randomly assigned to be irrigated with tap water (tap water group) and another 60 to be irrigated with 0·9% sodium chloride sterile solution (saline group), at a pressure of 0·46–0·54 PSI. Samples were collected from the centre of each wound using Levine's technique, before and after irrigation, and cultivated in thioglycollate, hypertonic mannitol agar, eosin methylene blue (EMB) agar, blood agar and Sabouraud agar at 37°C for 72 hours. There was concordance (kappa test) and discordance (McNemar test) regarding the count of positive and/or negative samples before and after irrigation in each group. The proportion of reduction of positive samples was similar for both groups in all cultures. Colony‐forming unit count before and after irrigation was similar in both groups and in all cultures, except for the culture in hypertonic mannitol agar from the tap water group, for which the count was lower after irrigation (Wilcoxon z = 2·05, P = 0·041). It is concluded that skin wound irrigation with tap water leads to further reduction of Gram‐positive bacteria compared with 0·9% sodium chloride sterile solution, with no difference in colonisation of haemolytic bacteria, Gram‐negative bacteria and fungi.
Evidence‐based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review
Authors: Kushnerev E. , Yates J. M. 
Published: June 2015

SummaryThe inferior alveolar nerve (IAN) and lingual (LN) are susceptible to iatrogenic surgical damage. Systematically review recent clinical evidence regarding IAN/LN repair methods and to develop updated guidelines for managing injury. Recent publications on IAN/LN microsurgical repair from Medline, Embase and Cochrane Library databases were screened by title/abstract. Main texts were appraised for exclusion criteria: no treatment performed or results provided, poor/lacking procedural description, cohort <3 patients. Of 366 retrieved papers, 27 were suitable for final analysis. Treatment type for injured IANs/LNs depended on injury type, injury timing, neurosensory disturbances and intra‐operative findings. Best functional nerve recovery occurred after direct apposition and suturing if nerve ending gaps were <10 mm; larger gaps required nerve grafting (sural/greater auricular nerve). Timing of microneurosurgical repair after injury remains debated. Most authors recommend surgery when neurosensory deficit shows no improvement 90 days post‐diagnosis. Nerve transection diagnosed intra‐operatively should be repaired in situ; minor nerve injury repair can be delayed. No consensus exists regarding optimal methods and timing for IAN/LN repair. We suggest a schematic guideline for treating IAN/LN injury, based on the most current evidence. We acknowledge that additional RCTs are required to provide definitive confirmation of optimal treatment approaches.
Little evidence of native and non‐native species influencing one another's abundance and distribution in the herb layer of an oak woodland
Authors: Davis Mark A. , Anderson Michael D. , Bock‐Brownstein Lilly , Staudenmaier Anna , Suliteanu Melena , Wareham Amanda , Dosch Jerald J. 
Published: June 2015

AbstractQuestionTo what extent are species, including native and non‐native species, influencing one another's distribution and abundance in the herb layer of a Minnesota oak woodland?LocationOak woodland succeeding into a more mesic forest, on bluffland of the Mississippi River, east‐central Minnesota.MethodsWe collected plant composition and species cover data in 182 1.0 × 0.5 m quadrats regularly spaced on a 6‐ha study grid in the oak woodland. We also recorded slope, slope position, aspect, elevation and photosynthetically active radiation (PAR) at each quadrat.ResultsPresence and abundance of other plant species, topographic variables and light availability explained only a small portion of the variation (5–19%) in the distribution and abundance of individual species. The most common strongest predictor of cover for the ten most common species was species richness, with the association being positive. The non‐native species, garlic mustard (Alliaria petiolata) exhibited the strongest positive association with species richness. Only one of the 45 pair‐wise comparisons of the ten species resulted in a negative relationship between the species. Abundance and distribution of two species were associated with topographic features, but this accounted for much less of the variation in abundance than did species richness.ConclusionWe found little evidence that competition or any other interactions among common herb layer species, including the non‐native Alliaria petiolata, play an important role in determining the abundance and the distribution of herb layer species in this oak woodland. Topographic factors may explain a small amount of the distribution and abundance patterns of a few species. But, for the most part, species are more likely to be present when other species are present, suggesting that they are simply establishing in microsites favourable to plants in general.
End-of-Car Device Condition Monitoring With Onboard Sensors
Authors: Hopkins Brad M. , Seidel Andrew , Maraini Dan , Shahidi Parham 
Published: June 2015

Draft gears and cushioning devices absorb energy during relative motion between two coupled railcars. This may occur in the form of buff and draft forces during over-the-track operation or impact forces during a coupling event in a switching yard. During such events, the end-of-car device absorbs energy that would otherwise be transmitted and possibly cause damage to the car body and/or lading. Health and performance of the end-of-car device is therefore of concern to shippers and car owners. Damaged cushioning units may be identified by visual inspection if the device is leaking hydraulic fluid or by a unit condition indicator, but may not be noticed until damage has been caused to the car and/or lading.
This paper presents the results of a study on the detection of a faulty end-of-car cushioning unit. A boxcar with 15 inch travel cushioning units installed on both ends was deployed for field service. The draft systems were inspected prior to the car being deployed, and although both ends of the car initially showed some signs of wear, there was evidence of heavier wear as well as signs of leaking on the B-end cushioning unit. The goal of the field trial was to determine whether or not the B-end of the car would produce higher magnitude acceleration events than the A-end during revenue service. Three wireless onboard monitoring systems, each with GPS and an accelerometer, were used to determine car location and measure car body accelerations. High car body accelerations were recorded and studied for a three month period of time. The results show that the onboard monitoring systems successfully detected more frequent and higher magnitude acceleration events on the B-end of the car.
Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty
Authors: Fredriksson Albin , Forsgren Anders , Hårdemark Björn 
Published: June 2015

Purpose:This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity‐modulated radiation therapy treatments subject to setup uncertainty.Methods:The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goals to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set.Results:Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account.Conclusions:Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.
Pharmacokinetic Modeling and Optimal Sampling Strategies for Therapeutic Drug Monitoring of Rifampin in Patients with Tuberculosis
Authors: Sturkenboom Marieke G. G. , Mulder Leonie W. , de Jager Arthur , van Altena Richard , Aarnoutse Rob E. , de Lange Wiel C. M. , Proost Johannes H. , Kosterink Jos G. W. , van der Werf Tjip S. , Alffenaar Jan-Willem C. 
Published: June 2015

ABSTRACT

Rifampin, together with isoniazid, has been the backbone of the current first-line treatment of tuberculosis (TB). The ratio of the area under the concentration-time curve from 0 to 24 h (AUC
0–24
) to the MIC is the best predictive pharmacokinetic-pharmacodynamic parameter for determinations of efficacy. The objective of this study was to develop an optimal sampling procedure based on population pharmacokinetics to predict AUC
0–24
values. Patients received rifampin orally once daily as part of their anti-TB treatment. A one-compartmental pharmacokinetic population model with first-order absorption and lag time was developed using observed rifampin plasma concentrations from 55 patients. The population pharmacokinetic model was developed using an iterative two-stage Bayesian procedure and was cross-validated. Optimal sampling strategies were calculated using Monte Carlo simulation (
n
= 1,000). The geometric mean AUC
0–24
value was 41.5 (range, 13.5 to 117) mg · h/liter. The median time to maximum concentration of drug in serum (
T
max
) was 2.2 h, ranging from 0.4 to 5.7 h. This wide range indicates that obtaining a concentration level at 2 h (
C
2
) would not capture the peak concentration in a large proportion of the population. Optimal sampling using concentrations at 1, 3, and 8 h postdosing was considered clinically suitable with an
r
2
value of 0.96, a root mean squared error value of 13.2%, and a prediction bias value of −0.4%. This study showed that the rifampin AUC
0–24
in TB patients can be predicted with acceptable accuracy and precision using the developed population pharmacokinetic model with optimal sampling at time points 1, 3, and 8 h.
Sequence Analysis of Herpes Simplex Virus 1 Thymidine Kinase and DNA Polymerase Genes from over 300 Clinical Isolates from 1973 to 2014 Finds Novel Mutations That May Be Relevant for Development of Antiviral Resistance
Authors: Schmidt Susanne , Bohn-Wippert Kathrin , Schlattmann Peter , Zell Roland , Sauerbrei Andreas 
Published: June 2015

ABSTRACTA total of 302 clinical herpes simplex virus 1 (HSV-1) strains, collected over 4 decades from 1973 to 2014, were characterized retrospectively for drug resistance. All HSV-1 isolates were analyzed genotypically for nonsynonymous mutations in the thymidine kinase (TK) and DNA polymerase (Pol) genes. The resistance phenotype against acyclovir (ACV) and/or foscarnet (FOS) was examined in the case of novel, unclear, or resistance-related mutations. Twenty-six novel natural polymorphisms could be detected in the TK gene and 69 in the DNA Pol gene. Furthermore, three novel resistance-associated mutations (two in the TK gene and one in the DNA Pol gene) were analyzed, and eight known but hitherto unclear amino acid substitutions (two encoded in TK and six in the DNA Pol gene) could be clarified. Between 1973 and 2014, the distribution of amino acid changes related to the natural gene polymorphisms of TK and DNA Pol remained largely stable. Resistance to ACV was confirmed phenotypically for 16 isolates, and resistance to ACV plus FOS was confirmed for 1 isolate. Acyclovir-resistant strains were observed from the year 1995 onwards, predominantly in immunosuppressed patients, especially those with stem cell transplantation, and the number of ACV-resistant strains increased during the last 2 decades. The data confirm the strong genetic variability among HIV-1 isolates, which is more pronounced in the DNA Pol gene than in the TK gene, and will facilitate considerably the rapid genotypic diagnosis of HSV-1 resistance.
Aerobactin, but Not Yersiniabactin, Salmochelin, or Enterobactin, Enables the Growth/Survival of Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae
Ex Vivo
and
In Vivo
Authors: Russo Thomas A. , Olson Ruth , MacDonald Ulrike , Beanan Janet , Davidson Bruce A. 
Published: June 2015

ABSTRACT

The siderophore aerobactin is the dominant siderophore produced by hypervirulent
Klebsiella pneumoniae
(hvKP) and was previously shown to be a major virulence factor in systemic infection. However, strains of hvKP commonly produce the additional siderophores yersiniabactin, salmochelin, and enterobactin. The roles of these siderophores in hvKP infection have not been optimally defined. To that end, site-specific gene disruptions were created in hvKP1 (wild type), resulting in the generation of hvKP1Δ
iucA
(aerobactin deficient), hvKP1Δ
iroB
(salmochelin deficient), hvKP1Δ
entB
(enterobactin and salmochelin deficient), hvKP1Δ
irp2
(yersiniabactin deficient), and hvKP1Δ
entB
Δ
irp2
(enterobactin, salmochelin, and yersiniabactin deficient). The growth/survival of these constructs was compared to that of their wild-type parent hvKP1
ex vivo
in human ascites fluid, human serum, and human urine and
in vivo
in mouse systemic infection and pulmonary challenge models. Interestingly, in contrast to aerobactin, the inability to produce enterobactin, salmochelin, or yersiniabactin individually or in combination did not decrease the
ex vivo
growth/survival in human ascites or serum or decrease virulence in the
in vivo
infection models. Surprisingly, none of the siderophores increased growth in human urine. In human ascites fluid supplemented with exogenous siderophores, siderophores increased the growth of hvKP1Δ
iucA
, with the relative activity being enterobactin > aerobactin > yersiniabactin > salmochelin, suggesting that the contribution of aerobactin to virulence is dependent on both innate biologic activity and quantity produced. Taken together, these data confirm and extend a role for aerobactin as a critical virulence factor for hvKP. Since it appears that aerobactin production is a defining trait of hvKP strains, this factor is a potential antivirulence target.
Hepatitis B Virus X Protein (HBx) Is Responsible for Resistance to Targeted Therapies in Hepatocellular Carcinoma: Ex Vivo Culture Evidence
Authors: Huang Pinbo , Zhuang Baoxiong , Zhang Heyun , Yan Haiyan , Xiao Zhiyu , Li Wenbin , Zhang Jianlong , Tang Qibin , Hu Kaishun , Koeffler H. Phillip , Wang Jie , Yin Dong 
Published: June 2015

Abstract
Purpose: Molecular targeted therapy is an important approach for advanced hepatocellular carcinoma (HCC). Hepatitis B virus–related HCC (HBV-HCC) accounts for approximately 50% of all HCC cases. Bortezomib, a proteasome inhibitor (PI), is used extensively for the treatment of hematologic malignancies, but its application in HCC, particularly in HBV-HCC, has not been fully explored.
Experimental Design: The effects of bortezomib on HCC tissues were evaluated by TUNEL assays. The growth inhibitory activity was measured using cell viability assays, and apoptosis was measured using flow cytometry. The levels of HBx, P-Raf/Raf, and P-Erk/Erk expression were measured by Western blot analysis. The ability of the MEK inhibitor PD98059 to enhance the cell killing activity of bortezomib was evaluated using ex vivo and in vivo methods.
Results: The potency of bortezomib varied among HCC samples and cell lines, and HBV/HBx expression was associated with resistance to bortezomib. Bortezomib increased the levels of P-Raf and P-Erk in HBV/HBx–positive cells but not in HBV/HBx–negative HCC cells or in breast cancer or glioblastoma multiform cells. HBx was also upregulated after exposure to bortezomib, which was associated with the inhibition of proteasome activity. P-Erk upregulation mediated by bortezomib was effectively suppressed by the addition of the MEK inhibitor PD98059. Moreover, bortezomib and PD98059 synergistically inhibited HCC cell proliferation, as measured using both ex vivo and in vivo models.
Conclusions: Our studies demonstrate for the first time that HBx causes resistance to bortezomib in HCC, and this resistance can be antagonized by a MEK signaling inhibitor, providing a novel therapeutic approach. Clin Cancer Res; 21(19); 4420–30. ©2015 AACR.