bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non‐muscle‐invasive bladder cancer treated with intravesical chemotherapy
Authors: Lammers Rianne J.M. , Palou Joan , Witjes Wim P.J. , Janzing‐Pastors Maria H.D. , Caris Christien T.M. , Witjes J. Alfred
Published: October 2013

Objective

To compare the risks according to the American Urological Association (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncologico (CUETO) classifications with real outcomes in a cohort of patients in the Netherlands, and to confirm that patients who were undertreated according to these risk models have worse outcomes than adequately treated patients.

Patients and Methods

Patients treated with complete transurethral resection of bladder tumour and intravesical chemotherapy were included.

Not all patients would have received intravesical chemotherapy had they been treated to current standards, and thus comparison of the observed outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables and CUETO scoring model was possible.

The cohort was reclassified according to the definitions of five index patients (IPs), as defined by the AUA guidelines, and three risk groups, defined according to the EAU guidelines, to compare the outcomes of undertreated patients with those of adequately treated patients.

Results

A total of 1001 patients were available for comparison with the AUA definitions and 728 patients were available for comparison with the EORTC and CUETO models.

There was a large overlap between the observed outcomes and expected recurrence and progression probabilities when comparison was made using the EORTC risk tables.

The observed recurrence outcomes were in general higher than the expected probabilities according to the CUETO risk classification, especially in the long term.

No differences in progression were found when comparing these two models to the Dutch cohort.

Patients who were undertreated according to the guidelines showed, in general, a higher risk of developing recurrence and progression.

Limitations are i.a. its retrospective nature and the differences in grading system.

Conclusion

Comparisons between the observed outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO risk models and the EORTC and AUA guidelines showed that lack of adherence to existing guidelines translates into worse outcomes.
Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for robot‐assisted laparoscopic surgery
Authors: Hefermehl Lukas J. , Largo Remo A. , Hermanns Thomas , Poyet Cédric , Sulser Tullio , Eberli Daniel
Published: October 2013

Objective

To assess critical heat spread of cautery instruments used in robot‐assisted laparoscopic (RAL) surgery.

Materials and Methods

Thermal spread along bovine musculofascial tissues was examined by infrared camera, histology and enzyme assay.

Currently used monopolar, bipolar and ultrasonic laparoscopic instruments were investigated at various power settings and application times.

The efficacy of using an additional Maryland clamp as a heat sink was evaluated.

A temperature of 45 °C was considered the threshold temperature for possible nerve damage.

Results

Monopolar instruments exhibited a mean (sem) critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s, the spread was >20 mm.

For adjustable bipolar instruments the mean (sem) critical thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s.

The PK and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8 (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm.

Application of an additional Maryland clamp as a heat sink, significantly reduced the thermal spread.

Histomorphometric analyses and enzyme assay supported these findings.

Conclusions

All coagulation devices used in RAL surgery have distinct thermal spreads depending on power setting and application time.

Cautery may be of concern due to lateral temperature spread, causing potential damage to sensitive structures including nerves.

Our results provide surgeons with a resource for educated decision‐making when using coagulation devices during robotic procedures.
Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumour antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides
Authors: Kawashima Hidenori , Obayashi Aiko , Kawamura Marie , Masaki Sakae , Tamada Satoshi , Iguchi Taro , Uchida Junji , Kuratsukuri Katsuyuki , Tanaka Tomoaki , Nakatani Tatsuya
Published: October 2013

Objective

To analyse and then generalize the mechanism by which partial or complete response is achieved among a limited number of patients with metastatic renal cell carcinoma (RCC) treated with interferon or interleukin‐2.

Materials and Methods

An expression library of RCC (clear‐cell carcinoma) was screened using the sera of patients with metastatic RCC who benefited from partial or complete response to cytokine therapy, the postulation being that those remarkable responders obtained specific cellular immunity against RCC with the antibodies to react with the cancer antigen.

Peripheral blood mononuclear‐cells (PBMCs) from healthy volunteers were stimulated with the antigen‐derived peptides to induce specific cytotoxic T lymphocytes (CTLs). Specific activities of CTLs were measured by 51Cr‐releasing assay.

Results

Among 15 positive clones isolated, two novel genes, galectin 9 and PINCH, were expressed at much higher levels in cancerous lesions than in normal tissues in all the patients with clear‐cell carcinoma who were examined.

Both HLA‐A*2402‐restricted and HLA‐A*0201‐restricted CTLs were induced by each antigen‐derived peptide to exhibit specific and highly cytotoxic activities towards RCC cells.

Specific CTLs were induced abundantly, as shown by flow cytometry analysis of the CTLs labelled with fluorescein isothiocyanate anti‐CD107a and APC anti‐CD8.

The clonal expansion of the CTLs was shown by the clonality of T‐cell receptor Vβ repertoires.

Conclusion

A novel approach based on clinical observations yielded promising tumour antigens as immunotherapy targets of RCC.
Impact of urinary incontinence on healthcare resource utilization, health‐related quality of life and productivity in patients with overactive bladder
Authors: Tang Derek H. , Colayco Danielle C. , Khalaf Kristin M. , Piercy James , Patel Vaishali , Globe Denise , Ginsberg David
Published: October 2013

Objective

To evaluate the impact of urinary incontinence (UI) on healthcare resource utilization (HRU), health‐related quality of life (HRQoL) and productivity measures in patients with overactive bladder (OAB).

Patients and Methods

This retrospective, cross‐sectional study used data from the Adelphi OAB/UI Disease Specific Programme, a multinational survey of patient‐ and physician‐reported data, fielded between November 2010 and February 2011.

The primary patient groups of interest were those with OAB, both with and without UI.

Health‐related quality of life and productivity measures were derived from the EuroQoL‐5D, the Incontinence Quality of Life questionnaire, the Overactive Bladder Questionnaire, and the Work Productivity and Activity Impairment Questionnaire.

Measures of HRU included OAB‐related surgeries, OAB‐related hospitalizations, incontinence pads, anticholinergic use and physician visits.

Multivariate linear regression models and literature‐based minimal clinically important differences were used to assess statistically significant and clinically meaningful differences in HRQoL and productivity measures between patients with OAB with UI and those without UI.

Results

A total of 1 730 patients were identified, with a mean age of 60.7 years, and 77.0% of them were women, 84.2% were non‐Hispanic whites, and 71% were incontinent.

Bivariate analyses showed that HRU was significantly higher among patients with OAB with UI than among those without UI in all categories except for the number of OAB‐related physician visits.

In both bivariate and multivariate analyses, incontinent patients presented with clinically and statistically significantly lower HRQoL and productivity measures with respect to all study endpoints, except for percentage of work time missed due to their OAB/UI.

Conclusions

Urinary incontinence was associated with significantly higher HRU and lower HRQoL and productivity in this population of patients with OAB from five different countries.

In addition to clinical considerations, the economic and humanistic impact of UI should be taken into account when evaluating treatment options for patients with OAB.
When Does Tool Use Become Distinctively Human? Hammering in Young Children
Authors: Kahrs Björn Alexander , Jung Wendy P. , Lockman Jeffrey J.
Published: October 2013

This study examines the development of hammering within an ontogenetic and evolutionary framework using motion‐capture technology. Twenty‐four right‐handed toddlers (19–35 months) wore reflective markers while hammering a peg into a peg‐board. The study focuses on the motor characteristics that make tool use uniquely human: wrist involvement, lateralization, and handle use. Older children showed more distally controlled movements, characterized by relatively more reliance on the wrist, but only when hammering with their right hand. Greater age, use of the right hand, and more wrist involvement were associated with higher accuracy; handle use did not systematically change with age. Collectively, the results provide new insights about the emergence of hammering in young children and when hammering begins to manifest distinctively human characteristics.
Asthma among workers in healthcare settings: role of disinfection with quaternary ammonium compounds
Authors: Gonzalez M. , Jégu J. , Kopferschmitt M.‐C. , Donnay C. , Hedelin G. , Matzinger F. , Velten M. , Guilloux L. , Cantineau A. , de Blay F.
Published: October 2013

Introduction

An increased incidence of asthma has been reported among healthcare workers. The role of quaternary ammonium compounds (QACs), commonly used in cleaning/disinfection products, has not been clearly defined. The aim of this study was to analyse associations between asthma and occupational exposure to disinfectants, especially QACs.

Methods

The study was performed on a stratified random sample of the various healthcare departments of 7 healthcare settings. The study included: questionnaire, physical examination and specific IgE assays. Occupational exposure assessment was performed by means of a work questionnaire, workplace studies and a review of products ingredients. Data were analysed by logistic regression.

Results

Response rate was 77%; 543 workers (89% female) participated; 37.1% were registered nurses (RNs), 16.4% auxiliary nurses (ANs), 17.3% cleaners; 32.8% were atopic. 335 participants were exposed to QACs. Nursing professionals reported a significantly higher risk of reported physician‐diagnosed asthma and, for RNs, of nasal symptoms at work than administrative staff working in healthcare sector. This risk was particularly marked during disinfection tasks and when exposure to QACs. Exposure to QACs increased significantly the risk of reported physician‐diagnosed asthma and nasal symptoms at work (adjusted OR = 7.5 and 3.2, respectively). No significant association was found with other exposures such as latex glove use, chlorinated products/bleach or glutaraldehyde.

Conclusion

RNs and ANs presented a higher risk of reported asthma than administrative staff. The highest risk was associated with tasks involving dilution of disinfection products by manual mixing, suggesting possible exposure to repeated peaks of concentrated products known to be strong respiratory irritants. Workplace interventions should be conducted to more clearly determine QAC exposure and improve disinfection procedures.
Emergence of New Onset substance use disorders among post‐weight loss surgery patients
Authors: Wiedemann A. A. , Saules K. K. , Ivezaj V.
Published: October 2013

What is already known about this subject

Elevated rates of substance use disorders (SUDs), particularly (but not only) alcohol use, are observed among post‐weight loss surgery (WLS) patients.

The development of SUDs among post‐WLS patients typically occurs 1–2 years post‐surgery.

Post‐WLS patients are developing SUD at a much later time of life than is typical of SUDs in the general population, suggesting they constitute a distinct SUD phenotype that is directly related to having undergone WLS.

What this study adds

Overall, findings suggest that post‐WLS patients are overrepresented in substance abuse treatment programmes, and the majority of them report no history of SUD before WLS.

Relative to non‐WLS patients in SUD treatment, post‐WLS patients in substance abuse treatment are disproportionally diagnosed with alcohol dependence, including alcohol withdrawal.

Post‐WLS patients may be at elevated risk for development of New Onset SUD in the absence of a prior SUD history; this group is phenotypically different from those with a history of substance abuse prior to surgery, and such patients may have unique treatment needs.

A comprehensive substance abuse treatment facility began observing increased admissions who reported histories of weight loss surgery (WLS). Emerging evidence suggests that roughly half of post‐WLS patients in substance abuse treatment developed their substance use disorder (SUD) after surgery. The present study examined differences between SUD patients who developed New Onset SUD after surgery and those with a reported SUD onset before WLS (SUD Hx+ group). Participants completed a questionnaire and participated in a semi‐structured interview. Data were also obtained from participants’ electronic medical records. Of the total treatment sample (n = 4658), 2.8% reported a history of WLS. Post‐WLS patients were significantly more likely to be diagnosed with alcohol use disorders (AUDs). Among post‐WLS patients who were interviewed (n = 56), 60% were classified as New Onset SUD, while only 40% were SUD Hx+. SUD Hx+ cases reported using significantly more types of substances than New Onset cases and were more likely to report pre‐surgical binge eating disorder (BED). Post‐WLS patients are overrepresented in substance abuse treatment and are disproportionally diagnosed AUDs. Post‐WLS patients may be at elevated risk for development of New Onset SUD at a time in life (middle age) when SUD onset is relatively uncommon.
Visual disorders in children with cerebral palsy: is the picture still ‘blurred’?
Authors: Guzzetta Andrea
Published: October 2013

This commentary is on the original article by Pansell et al. on pages 171–177 of this issue.
Assessment of autism in children with visual impairment
Authors: Matsuba Carey A
Published: October 2013

This commentary is on the original article by Williams et al. on pages 66–72 of this issue.
User Cost Elasticity of Capital Revisited
Authors: Dwenger Nadja
Published: October 2013

Researchers still lack consensus about the size of the user cost elasticity of capital. The divergence in prior estimates may have arisen because one of the two strands of research has neglected cointegration among capital, its user costs, and sales. Using German firm‐level panel data, I show that estimating a distributed lag model, prevalent in prior literature, leads to low estimates of the user cost elasticity. Properly accounting for cointegration in an error correction model yields a much larger point estimate of the price elasticity of capital (close to −1). Non‐random sample attrition is found to be relatively unimportant.
Peak Myocardial Acceleration during Isovolumic Relaxation Time Predicts the Occurrence of Rehospitalization in Chronic Heart Failure: Data from the Daunia Heart Failure Registry
Authors: Correale Michele , Totaro Antonio , Ferraretti Armando , Passero Tommaso , De Rosa Fiorella , Musaico Francesco , Ieva Riccardo , Biase Matteo Di , Brunetti Natale Daniele
Published: October 2013

Background

Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of new developed TDI parameters, however, still needs to be documented.

Methods

A total of 113 consecutive patients with CHF enrolled in the Daunia heart failure registry underwent echocardiography assessment and were followed prospectively for 234 ± 262 days. Conventional echocardiography and TDI parameters were calculated. We also calculated peak myocardial acceleration during isovolumic relaxation time (pIVA[r]) derived from TDI (pIVV(r)/AT).

Results

Subjects readmitted for worsening HF were characterized by lower levels of pIVA(r) (0.8 ± 0.3 vs. 1.3 ± 0.5 m/s2, P < 0.001). pIVA(r) levels predicted the incidence of readmission for worsening HF during follow‐up (HR 0.78, 95% confidence interval 0.64–0.96, P < 0.05), even after multivariable analysis. The assessment of pIVA(r) in addition to left ventricular ejection fraction (LVEF) and E/E′ provided additional prognostic value (Log Rank P < 0.05). The presence of abnormal pIVA(r), LVEF, and E/E′ levels identified subjects with a higher risk of hospitalization for worsening dyspnea during follow‐up than those with 2 abnormal marker levels or 0–1 (Log Rank P < 0.05).

Conclusions

Peak myocardial acceleration during isovolumic relaxation time may represent an independent adjunctive tool for the risk stratification of patients with CHF.
Measurement of Left and Right Atrial Volume in Patients Undergoing Ablation for Atrial Arrhythmias: Comparison of a Manual versus Semiautomatic Algorithm of Real Time 3D Echocardiography
Authors: Müller Hajo , Reverdin Stéphane , Burri Haran , Shah Dipen , Lerch René
Published: October 2013

Aims

Real time full‐volume 3D echocardiography (3DE) allows rapid and noninvasive measurement of left (LA) and right atrial (RA) volume without geometric assumptions. Different algorithms from different commercial providers are available. Older software requires manual tracing of endocardial contours. Recently, software with semiautomatic endocardial contour‐finding algorithms has become available, which considerably speeds up the procedure. Our aim was to compare, in the same dataset, both LA and RA volumes determined by an algorithm involving manual tracing to the corresponding volumes obtained by an algorithm with semiautomatic contour detection.

Methods

Maximal atrial volumes were measured in 88 patients using a multiplane interpolation method algorithm based on manual planimetry of 8 slices. These volumes were compared with volumes determined by the QLAB 8.1 software using semiautomatic border detection.

Results

Linear regression showed excellent correlation between volumes determined by manual and by semiautomatic software for both LA and RA (r2 = 0.90 and 0.89, respectively, P < 0.001). Bland–Altman analysis of manual versus semiautomatic volume determination showed narrow 95% limits of agreement (−15.9 to +12.0 mL for LA volume and −13.9 to +12.2 mL for RA volume) with a minimal bias of −1.9 ± 7.0 mL and −0.8 ± 6.5 mL, respectively, by the semiautomatic method.

Conclusion

The semiautomatic border detection method shows excellent correlation for maximal LA and RA volume determination compared to the more time‐consuming, multiplane interpolation method, with only slight underestimation. The results indicate that values of LA and RA volumes obtained by either algorithm can be compared, for example, during follow‐up examinations.
The impact of activated carbon on NO3−‐N, NH4+‐N, P and K leaching in relation to fertilizer use
Authors: Raave H. , Keres I. , Kauer K. , Nõges M. , Rebane J. , Tampere M. , Loit E.
Published: October 2013

The ability of light‐textured soils to retain nutrients and water is small. In agriculture such soils pose a risk of nutrient leaching when amended with fertilizers. This study investigated the effects of the incorporation of activated carbon (AC) into the soil to determine (i) if it would decrease leaching of major nutrient ions and (ii) if its effect on leaching is influenced by fertilizer use. Nitrate nitrogen (NO3−‐N), ammonium nitrogen (NH4+‐N), phosphorus (P) and potassium (K) leaching through two substrates (sandy loam soil (S) and a sandy loam soil mixed with activated carbon (S + AC), which were unfertilized (NF or control) or fertilized with inorganic fertilizer (F), pig slurry (PS), pig slurry digestate (PD) or sewage sludge digestate (SD) was studied using mini‐lysimeters. In soil enriched with AC mark K‐835, water percolation and NO3−‐N and P leaching were significantly reduced, and K leaching was increased. Ammonium nitrogen leaching was not influenced by the AC amendment. The impact of AC on NO3−‐N and P leaching and water percolation did not change during the two‐year period, from which it is concluded that AC mark K‐835 prevents the leaching of NO3−‐N and P and increases soil water retention ability, and thus it is beneficial for light‐textured soils.
Opioids in Headache
Authors: Levin Morris
Published: October 2013

Opioid analgesics have long been used to treat head pain of various types. This has been increasing to a significant degree over the past 25 years because of a trend for more liberal use of opioids in non‐malignant pain. Opioid treatment for acute headache, as well as prophylactically for refractory chronic headache, is controversial. There are a number of adverse effects associated with acute and chronic opioid treatment. Tolerance, dependence, and addiction are prominent issues. This article attempts to analyze the benefits and disadvantages for opioids in the management of migraine and other headache disorders, relying on known properties of this class of medication as well as clinical data. It will mainly focus on 2 topics: the use of opioid medication for the acute treatment of migraine attacks and continuous prophylactic use for refractory chronic migraine.
Thiessen polygons as a model for animal territory estimation
Authors: Schlicht Lotte , Valcu Mihai , Kempenaers Bart
Published: October 2013

Thiessen polygons are often used to model territory characteristics. However, information about the quality of Thiessen polygon‐based estimates is currently lacking. We used published data to investigate the match between Thiessen polygons and mapped bird territories regarding territory size, shape and neighbourhood. Although territory sizes and the number of neighbours were strongly correlated between these two methods, both parameters were overestimated by the Thiessen polygons. Therefore, caution is required when Thiessen polygons are used as a model for absolute values and when the assumptions of Thiessen polygons, such as formation of discrete territories and a contiguous study area, are not met.
Factors associated with oral hygiene practices among adults with systemic sclerosis
Authors: Yuen HK , Hant FN , Hatfield C , Summerlin LM , Smith EA , Silver RM
Published: October 2013

Objective

To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc).

Methods

In this cross‐sectional study, 178 dentate adults with SSc received an oral examination which included measurement of oral aperture, assessment of manual dexterity to perform oral hygiene, as well as completion of the Center of Epidemiological Studies Depression (CES‐D) Scale and an oral health‐related questionnaire.

Results

Multivariable logistic regression modelling showed male, minority and high CES‐D scores (i.e. clinically significant symptoms of depression) were associated with less likelihood of participants brushing teeth at least twice daily, but the presence of self‐reported dry mouth symptoms increased the likelihood of toothbrushing. Having a dental visit in the past 12 months and use of an adapted flossing or interdental cleaning device were significantly associated with daily dental flossing; however, having difficulty flossing teeth reduced the likelihood of daily flossing.

Conclusions

Overall, demographic variables were strongly associated with toothbrushing frequency, whereas flossing self‐efficacy and barriers were strongly associated with dental flossing frequency in adults with SSc. The results suggest that dental health professionals should take mental health into consideration when educating patients with SSc to improve their oral hygiene and consider making referrals for patients exhibiting suspected clinically significant depressive symptoms to mental health professionals for further evaluation and treatment. In addition, an appropriate adapted flossing or interdental cleaning device should be recommended to increase dental flossing practices in this patient population.
Subcutaneous connective tissue reactions to iRoot SP, mineral trioxide aggregate (MTA) Fillapex, DiaRoot BioAggregate and MTA
Authors: Bósio C. C. , Felippe G. S. , Bortoluzzi E. A. , Felippe M. C. S. , Felippe W. T. , Rivero E. R. C.
Published: October 2013

Aim

To evaluate connective tissue reactions to iRoot SP (Innovative Bioceramics, Vancouver, BC, Canada), mineral trioxide aggregate (MTA) Fillapex (FLPX) (Angelus Soluções Odontológicas, Londrina, Brazil), DiaRoot Bioaggregate (DiaDent Group International, Burnaby, BC, Canada) and white MTA (Angelus, Londrina, Brazil) in Wistar rats.

Methodology

A total of 128 dentine tubes filled with the materials and 32 empty tubes (control) were implanted into 32 rats. After 7, 15, 30 and 90 days (n = 8 per period), the animals were euthanized, and the tissues were processed for histological evaluation using haematoxylin‐eosin (H&E) and Von Kossa (VK) staining. Observations were made for cellular inflammatory components and the presence of multinucleated giant cells (MNGC), macrophages and tissue necrosis. Data were analysed by Fisher's exact and Kruskal–Wallis tests (P < 0.05).

Results

In all experimental periods, MTA FLPX and iRoot SP scored higher than the other groups for the variable macrophages (P < 0.05). After 30‐ and 90‐day experimental periods, MTA FLPX scored higher than the other groups for the variable MNGC (P < 0.05). After 90 days, the only group that exhibited samples with severe inflammatory response was MTA FLPX. VK positivity was observed in areas of necrosis in all groups, except in the control group.

Conclusions

The materials were considered biologically acceptable except MTA FLPX, which remained toxic to subcutaneous tissue even after 90 days.
MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils
Authors: Bezerra da Silva R. A. , Nelson‐Filho P. , Lucisano M. P. , De Rossi A. , de Queiroz A. M. , Bezerra da Silva L. A.
Published: October 2013

Aim

To characterize the formation and progression of experimentally induced periapical lesions in teeth of MyD88 knockout (MyD88 KO) mice compared with wild‐type (WT) mice.

Methodology

Periapical lesions were induced in the mandibular first molars of 30 WT and 30 MyD88 KO mice. After 7, 21 and 42 days, the animals were euthanized and the mandibles were subjected to histotechnical processing. Histological sections were stained with haematoxylin and eosin (HE), TRAP histoenzymology, Brown and Brenn staining and immunohistochemistry (RANK, RANKL, OPG). Data were subjected to statistical analysis by the nonparametric Mann–Whitney and Kruskal–Wallis tests and the Dunn post‐test, using the SPSS software, version 17.0 (α = 0.05).

Results

Regarding the periapical lesion size, the MyD88 KO group had significantly higher values than the WT group in the periods of 7 (P = 0.001) and 21 days (P = 0.05). A larger number of neutrophils in the MyD88 KO group were observed (P = 0.01 at 7 days, P = 0.004 at 21 days and P < 0.001 at 42 days). Regarding the number of osteoclasts, no statistically significant difference was observed between the groups at any of the experimental periods (P = 0.884 at 7 days, P = 0.506 at 21 days and P = 0.211 at 42 days).

Conclusions

In the absence of MyD88, the animals had larger periapical lesions, with a severe inflammatory infiltrate and a significantly larger number of neutrophils.
Intravenous immunoglobulin modulates the expansion and cytotoxicity of CD8+ T cells
Authors: Trépanier Patrick , Chabot Dominique , Bazin Renée
Published: October 2013

Intravenous immunoglobulin (IVIg) is successfully used in the treatment of autoimmune diseases involving self‐reactive CD8+ T cells. However, its direct influence on the cytotoxic response remains unknown. Using an antigen cross‐presentation assay and a mouse model of ovalbumin (OVA) immunization, we showed that IVIg decreases the in vitro activation, proliferation and cytokine secretion of OVA‐specific CD8+ T cells (OT‐I), as well as the in vivo generation of OVA‐specific CD8+ T cells. In addition, IVIg significantly decreases the proportion of perforin‐ and CD107a‐expressing CD8+ T cells, and inhibits the cytotoxic activity of OVA‐activated OT‐I cells. The interference of IVIg with the CD8+ T‐cell response is associated with T‐cell receptor blockade, therefore reducing the interaction between effector and target cells. A similar blockade is observed on human CD8+ T cells, suggesting that the observations reported here could apply to the IVIg‐mediated improvement of CD8+ T‐cell‐mediated autoimmune conditions in human patients.
Use of recombinant activated factor VII in Jehovah's Witness patients with critical bleeding
Authors: Kandane‐Rathnayake Rangi K. , Isbister James P. , Zatta Amanda J. , Aoki Naomi J. , Cameron Peter , Phillips Louise E. ,   on behalf of the Australian and New Zealand Haemostasis Registry Steering Committee
Published: October 2013

Introduction

The Australian and New Zealand Haemostasis Registry (ANZHR) included patients who received off‐licence recombinant activated factor VII (rFVIIa) for critical bleeding from 2000 to 2009. Approximately 1.3% of the ANZHR patients were Jehovah's Witnesses (JWs). We compared them with the non‐JW patients in the registry.

Methods

Patient characteristics (e.g. gender, context of bleeding), factors influencing rFVIIa use (e.g. body temperature and pH) and outcomes (e.g. bleeding response (stopped/attenuated or unchanged) to rFVIIa, mortality) were compared between JW and non‐JW patients using Fisher's exact chi‐square tests and Kruskal‐Wallis tests.

Results

A total of 42 JW and 3134 non‐JW patients were included in the analysis. Approximately 99% (n = 3098) of non‐JWs received blood products compared with only 30% (n = 13) of JWs (P < 0.01). The distribution of gender and contexts of critical bleeding in the two groups was significantly different. Approximately 17% of the non‐JW patients were hypothermic (T < 35°C) and about 19% were acidotic (pH < 7.2) at the time of initial rFVIIa administration. Conversely, none of the JWs were hypothermic and only one was acidotic. The proportion of positive responders to rFVIIa (stopped/attenuated bleeding following rFVIIa use) was similar in both groups (75% non‐JWs, 74% JWs; P = 1.0). Approximately 28% of non‐JW and 17% of JW patients were deceased by day 28 following rFVIIa use (P = 0.16).

Discussion

Several factors were observed to be significantly different between JW and non‐JW patients, yet the proportions of responders to rFVIIa were similar in both groups. The actual factors influencing response to rFVIIa are yet to be determined.
HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality
Authors: Klein MB , Rollet KC , Saeed S , Cox J , Potter M , Cohen J , Conway B , Cooper C , Côté P , Gill J , Haase D , Haider S , Hull M , Moodie E , Montaner J , Pick N , Rachlis A , Rouleau D , Sandre R , Tyndall M , Walmsley S ,   Canadian HIV‐HCV Cohort Investigators
Published: October 2013

Objectives

Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV‐coinfected Canadians.

Methods

HIV/HCV‐coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all‐cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population.

Results

A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5–2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self‐identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person‐years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%).

Conclusions

We observed excessive morbidity and mortality in this HIV/HCV‐coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV‐coinfected persons.
Multiple nutrients and herbivores interact to govern diversity, productivity, composition, and infection in a successional grassland
Authors: Borer Elizabeth T. , Seabloom Eric W. , Mitchell Charles E. , Cronin James P.
Published: October 2013

In spite of increasing awareness that interactions between herbivory and the supply rates of multiple nutrients control biodiversity, ecosystem functions and ecosystem services in ecological communities, few experimental studies have concurrently examined the independent and joint effects of multiple nutrients and mammalian consumers on these responses in natural systems. Here we quantify the independent and interactive effects of multiple concurrent changes to resources and consumers in an invaded annual grassland community in California. In a two‐year study using thirty‐seven 400‐m2 plots, we examine interactions among four nutrient treatments (N, P, K and micronutrients) and a keystone herbivore (pocket gopher Thomomys bottae) on four plant community outcomes: 1) plant diversity, 2) functional group composition, 3) net biomass production, an important ecosystem function, and 4) infection risk by a group of viral pathogens shared by crop and non‐crop grasses (barley and cereal yellow dwarf viruses), an important regulating ecosystem service. We found that grassland biodiversity and infection risk were controlled by nutrient identity and supply ratio whereas nutrients interacted strongly with consumers to control grassland composition and net primary productivity. The most important insights arising from this multi‐factor experiment are that net biomass production increased with phosphorus or nitrogen supply; however, when gophers were present, nitrogen caused no net effect on biomass production. In addition, infection risk was driven by phosphorus, nitrogen and micronutrient supply. Infection in a sentinel host increased strongly with the addition of micronutrients or phosphorus; however, infection declined with increasing N/P supply ratio, indicating stoichiometric control of infection risk. Finally, in spite of manipulating multiple factors, plant species richness declined with nitrogen, alone. The importance of higher‐order interactions demonstrates that a multi‐factor approach is critical for effective predictions in a world in which anthropogenic activities are simultaneously changing herbivore abundance and the relative supply of many nutrients.
Combining Stocks and Flows of Knowledge: The Effects of Intra‐Functional and Cross‐Functional Complementarity
Authors: Ambos Tina C. , Nell Phillip C. , Pedersen Torben
Published: October 2013

While previous research has mostly focused on either knowledge stocks or knowledge flows, our study is among the first to integrate these perspectives in order to shed light on the complementarity effects of different types of knowledge stocks and flows in the multinational corporation (MNC). This study investigates intra‐functional as well as cross‐functional complementarity effects from the perspective of the knowledge recipient and tests their impact on the benefit created for MNC units. Based on a comprehensive sample of 324 relationships between MNC units, we find that both types of complementarity create benefits for these units, but that the effects from intra‐functional combinations of knowledge stocks and flows are significantly stronger than from cross‐functional combinations.
Preferences, Structure, and Influence: The Engineering of Consent
Authors: Henisz Witold J.
Published: October 2013

I present a decision process framework that informs the design and implementation of stakeholder influence strategy. This process combines insights from agent‐based dynamic utility and dynamic network processes. Stakeholders strategically seek an outcome as close as possible to their preferred point but also wish to be on the winning side and not to pursue positions divergent from stakeholders with whom they have strong affective ties. Simulation analysis highlights important effects from embedding stakeholders within such an interdependent policymaking network. The resulting decision process framework can be used by firms to assess the likely dynamics within such a stakeholder network as well as to compare alternative treatments to that network for their efficacy in securing a favorable policy outcome, collective decision, or shift in group opinion.
Effect of Ca2+ Substitution on the Structure, Microstructure, and Microwave Dielectric Properties of Sr2Al2SiO7 Ceramic
Authors: Manu Kurusaroor Mana , Karthik Chinnathambi , Ubic Rick , Sebastian Mailadil Thomas
Published: October 2013

The effect of Ca2+ substitution on the structure, microstructure, and microwave dielectric properties of Sr–gehlenite (Sr2Al2SiO7) ceramic has been investigated. The structure and microstructure of Sr2−xCaxAl2SiO7 ceramics were analyzed via X‐ray diffraction (XRD) as well as scanning and transmission electron microscopic techniques. While the end‐members (x = 0 and 2) form isostructural compounds, a highly defective, nonstoichiometric, Ca‐rich secondary phase was observed via bright‐field transmission electron microscopy and energy dispersive X‐ray spectroscopy in compositions corresponding to x = 0.75 and 1.5. The concentration of secondary phase in x = 0.75 is too low to be detected via XRD or scanning electron microscopy. Identical selected‐area electron‐diffraction patterns of the compounds (x = 0, 1, and 2) confirmed that they belong to the space group P21m (no. 113) with tetragonal crystal symmetry. The porosity‐corrected relative permittivity at microwave frequencies showed a gradual increase with Ca2+ content; however, Ca2+ substitution made only marginal changes to the microwave dielectric properties except in the case of x = 1.5, in which the secondary phase reduced the quality factor considerably. Thermal conductivity decreased with increasing Ca2+ content, and the compounds with defective structures showed the lowest thermal conductivity. All the compounds exhibited low coefficients of linear thermal expansion, with values varying in the range 2.3–3.6 ppm/°C.
Grain Size Effects on Piezoelectric Properties and Domain Structure of BaTiO3 Ceramics Prepared by Two‐Step Sintering
Authors: Huan Yu , Wang Xiaohui , Fang Jian , Li Longtu
Published: October 2013

A series of highly dense barium titanate (BaTiO3) ceramics with the average grain size (GS) from 0.29 to 8.61 μm are successfully prepared by two‐step sintering, and the GS effect on piezoelectric coefficient (d33) is systematically discussed in this work. It is found that when GS above 1 μm, d33 can be enhanced with decreasing GS, reaching a maximum value of 519 pC/N around 1 μm due to the high activity of domain wall mobility. Subsequently, d33 rapidly drops with a further decrease in GS owing to the reduced domain density. The results suggest that it is possible to prepare high‐performance BaTiO3 ceramics by controlling the GS and domain configuration properly, which brings great revitalization to the BaTiO3‐based piezoceramics.
Thermodynamics of Nanoscale Calcium and Strontium Titanate Perovskites
Authors: Sahu Sulata K. , Maram Pardha S. , Navrotsky Alexandra
Published: October 2013

The surface enthalpies of nanocrystalline CaTiO3 and SrTiO3 perovskites were determined using high‐temperature oxide melt solution calorimetry in conjunction with water adsorption calorimetry. The nanocrystalline samples were synthesized by a hydrothermal method and characterized using powder X‐ray diffraction, FTIR spectroscopy, and Brunauer–Emmett–Teller surface area measurements. The integral heats of water vapor adsorption on the surfaces of nanocrystalline CaTiO3 and SrTiO3 are −78.63 ± 4.71 kJ/mol and −69.97 ± 4.43 kJ/mol, respectively. The energies of the hydrous and anhydrous surfaces are 2.49 ± 0.12 J/m2 and 2.79 ± 0.13 J/m2 for CaTiO3 and 2.55 ± 0.15 J/m2 and 2.85 ± 0.15 J/m2 for SrTiO3, respectively. The stability of the perovskite compounds in this study is discussed according to the lattice energy and tolerance factor approach. The energetics of different perovskites suggest that the formation enthalpy becomes more exothermic and surface energy increases with an increase in ionic radius of the “A” site cation (Ca, Sr, and Ba), or with the tolerance factor. PbTiO3 shows a lower surface energy, weaker water binding, and a less exothermic enthalpy of formation than the alkaline‐earth perovskites.
Effects of marginality on plant population performance
Authors: Abeli Thomas , Gentili Rodolfo , Mondoni Andrea , Orsenigo Simone , Rossi Graziano
Published: October 2013

Aim

Populations at the edge of a species' distribution range may differ substantially from central populations. Peripheral populations may have either a high evolutionary potential or be prone to extinction, but the processes driving these outcomes are still unclear. Peripheral plant populations have been the subject of numerous studies and reviews, with many focusing on their genetic characteristics. In this review, we consider the effect of marginality on demographic species‐specific traits.

Location

World‐wide.

Methods

We reviewed the literature based on direct comparisons between central and peripheral plant populations. Strict inclusion criteria were applied to avoid biased analysis that may arise as a result of inaccurate boundary considerations or inappropriate comparisons. We inferred from the published data whether a certain trait had a better performance in central or peripheral populations (reliability of the abundant centre hypothesis,ACH).

Results

There have not been enough studies on plant performance to allow for generalizations on the effects of marginality on plants.ACHexpectations were not met in most cases and specific responses to marginality were observed at the species and population levels. Population and plant size more often met theACHassumptions, suggesting that most geographically peripheral populations are also ecologically marginal. The availability of resources, the reproductive strategy, the level of ploidy and the ability to cope with interspecific competitors seem to drive the numerous exceptions to theACHexpectations.

Main conclusions

The large numbers of exceptions to theACHexpectations suggest that a new comprehensive theory is needed to explain the effects of marginality in plants and to identify any general patterns. From the theoretical point of view, we propose that population history and dynamics should be considered when attempting to explain the processes that occur in peripheral plant populations.
Parental separation/divorce in childhood and partnership outcomes at age 30
Authors: Fergusson David M. , McLeod Geraldine F. H. , John Horwood L.
Published: October 2013

Background

Previous research has found that children exposed to separation/divorce may also experience relationship problems in adulthood. The aim of this investigation was to examine this issue in a birth cohort of over 900 New Zealand children studied to age 30.

Methods

Data were gathered over the course of the Christchurch Health and Development Study (CHDS). The CHDS is a 30 year longitudinal study of a birth cohort of 1265 children born in Christchurch (NZ) in 1977. The data collected included the following: (a) timing and number of parental separations and divorces from birth to 15 years; (b) partnership outcomes (16–30 years) of the number of cohabiting/marriage partnerships; positive partner relations; negative partner relations; partner adjustment/conduct problems; and interpartner violence victimization and perpetration; and (c) potential covariate factors.

Results

Study findings showed the presence of significant associations between childhood parental separations/divorces and number of cohabiting/marriage partnerships (16–30 years) (p < .001), negative partner relations (p = .021), extent of partner adjustment/conduct problems (p < .001), and perpetration of interpartner violence (p = .018). Childhood parental separation/divorce explained less than 2.5% of the variance in partnership outcomes. These associations were explained statistically by a series of covariate factors associated with childhood parental separation/divorce including parental history of illicit drug use, childhood sexual abuse, childhood conduct problems (7–9 years), interparental conflict and violence, childhood physical punishment/maltreatment, family socio‐economic status at the child's birth, and parental history of criminality. Tests of gender interaction showed that the effect of childhood parental separations/divorces may be the same for males and females. Analysis of the number of childhood parental separations/divorces experienced into three age groups (birth to 5, 5–10 years and 10–15 years) yielded similar results.

Conclusions

These findings suggest that the general associations between childhood parental separation/divorce and partner relationships in adulthood reflect the consequences of various contextual factors that are associated with childhood parental separation.
Widespread phenotypic and genetic divergence along altitudinal gradients in animals
Authors: Keller I. , Alexander J. M. , Holderegger R. , Edwards P. J.
Published: October 2013

Altitudinal gradients offer valuable study systems to investigate how adaptive genetic diversity is distributed within and between natural populations and which factors promote or prevent adaptive differentiation. The environmental clines along altitudinal gradients tend to be steep relative to the dispersal distance of many organisms, providing an opportunity to study the joint effects of divergent natural selection and gene flow. Temperature is one variable showing consistent altitudinal changes, and altitudinal gradients can therefore provide spatial surrogates for some of the changes anticipated under climate change. Here, we investigate the extent and patterns of adaptive divergence in animal populations along altitudinal gradients by surveying the literature for (i) studies on phenotypic variation assessed under common garden or reciprocal transplant designs and (ii) studies looking for signatures of divergent selection at the molecular level. Phenotypic data show that significant between‐population differences are common and taxonomically widespread, involving traits such as mass, wing size, tolerance to thermal extremes and melanization. Several lines of evidence suggest that some of the observed differences are adaptively relevant, but rigorous tests of local adaptation or the link between specific phenotypes and fitness are sorely lacking. Evidence for a role of altitudinal adaptation also exists for a number of candidate genes, most prominently haemoglobin, and for anonymous molecular markers. Novel genomic approaches may provide valuable tools for studying adaptive diversity, also in species that are not amenable to experimentation.