bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death
Authors: Nassar Ahmed , Liu Qiang , Farias Kevin , Buccini Laura , Baldwin William , Bennett Ana , Mangino Martin , Irefin Samuel , Cywinski Jacek , Okamoto Toshihiro , Diago Uso Teresa , Iuppa Giuseppe , Soliman Basem , Miller Charles , Quintini Cristiano
Published: April 2016

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.
Experimental and Numerical Investigation of an Axial Rotary Blood Pump
Authors: Schüle Chan Yong , Thamsen Bente , Blümel Bastian , Lommel Michael , Karakaya Tamer , Paschereit Christian Oliver , Affeld Klaus , Kertzscher Ulrich
Published: April 2016

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near‐wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds‐averaged Navier–Stokes simulations‐computational fluid dynamics (URANS‐CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall‐particle image velocimetry technique, and the visualization of near‐wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS‐CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.
Inulin significantly improves serum magnesium levels in proton pump inhibitor‐induced hypomagnesaemia
Authors: Hess M. W. , de Baaij J. H. F. , Broekman M. , Bisseling T. M. , Haarhuis B. , Tan A. , te Morsche R. , Hoenderop J. G. J. , Bindels R. J. M. , Drenth J. P. H.
Published: April 2016

Background

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid‐related disorders. PPI‐induced hypomagnesaemia, a defect in intestinal absorption of Mg2+, can be a severe side effect of chronic PPI use.

Aim

To restore serum Mg2+ concentrations in PPI‐induced hypomagnesaemia patients by dietary supplementation with inulin fibres.

Methods

Eleven patients with PPI‐induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14‐day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg2+ levels served as the primary endpoint.

Results

Inulin significantly enhanced serum Mg2+ levels from 0.60 to 0.68 mmol/L in PPI‐induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg2+ excretion was significantly increased in patients with PPI‐induced hypomagnesaemia (0.3–2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin.

Conclusion

Inulin increases serum Mg2+ concentrations under PPI maintenance in patients with PPI‐induced hypomagnesaemia.
Systematic review: current concepts and challenges for the direct‐acting antiviral era in hepatitis C cirrhosis
Authors: Majumdar A. , Kitson M. T. , Roberts S. K.
Published: April 2016

Background

The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct‐acting anti‐viral (DAA) therapy provides effective treatment for patients with cirrhosis.

Aim

To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population.

Methods

A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross‐referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir.

Results

Successful direct‐acting anti‐viral treatment is now possible in patients with HCV‐related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90–95%. Overall success rates in GT1 cirrhosis are excellent while GT3‐infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%.

Conclusions

Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard‐to‐cure groups of GT3 cirrhosis and direct‐acting anti‐viral failures, and managing drug–drug interactions.
Identification of cooperative genes for E2A‐PBX1 to develop acute lymphoblastic leukemia
Authors: Sera Yasuyuki , Yamasaki Norimasa , Oda Hideaki , Nagamachi Akiko , Wolff Linda , Inukai Takeshi , Inaba Toshiya , Honda Hiroaki
Published: April 2016

E2A‐PBX1 is a chimeric gene product detected in t(1;19)‐bearing acute lymphoblastic leukemia (ALL) with B‐cell lineage. To investigate the leukemogenic process, we generated conditional knock‐in (cKI) mice for E2A‐PBX1, in which E2A‐PBX1 is inducibly expressed under the control of the endogenous E2A promoter. Despite the induced expression of E2A‐PBX1, no hematopoietic disease was observed, strongly suggesting that additional genetic alterations are required to develop leukemia. To address this possibility, retroviral insertional mutagenesis was used. Virus infection efficiently induced T‐cell, B‐cell, and biphenotypic ALL in E2A‐PBX1 cKI mice. Inverse PCR identified eight retroviral common integration sites, in which enhanced expression was observed in the Gfi1, Mycn, and Pim1 genes. In addition, it is of note that viral integration and overexpression of the Zfp521 gene was detected in one tumor with B‐cell lineage; we previously identified Zfp521 as a cooperative gene with E2A‐HLF, another E2A‐involving fusion gene with B‐lineage ALL. The cooperative oncogenicity of E2A‐PBX1 with overexpressed Zfp521 in B‐cell tumorigenesis was indicated by the finding that E2A‐PBX1 cKI, Zfp521 transgenic compound mice developed B‐lineage ALL. Moreover, upregulation of ZNF521, the human counterpart of Zfp521, was found in several human leukemic cell lines bearing t(1;19). These results indicate that E2A‐PBX1 cooperates with additional gene alterations to develop ALL. Among them, enhanced expression of ZNF521 may play a clinically relevant role in E2A fusion genes to develop B‐lineage ALL.
Dual preventive benefits of iron elimination by desferal in asbestos‐induced mesothelial carcinogenesis
Authors: Jiang Li , Chew Shan‐Hwu , Nakamura Kosuke , Ohara Yuuki , Akatsuka Shinya , Toyokuni Shinya
Published: April 2016

Asbestos‐induced mesothelial carcinogenesis is currently a profound social issue due to its extremely long incubation period and high mortality rate. Therefore, procedures to prevent malignant mesothelioma in people already exposed to asbestos are important. In previous experiments, we established an asbestos‐induced rat peritoneal mesothelioma model, which revealed that local iron overload is a major cause of pathogenesis and that the induced genetic alterations are similar to human counterparts. Furthermore, we showed that oral administration of deferasirox modified the histology from sarcomatoid to the more favorable epithelioid subtype. Here, we used i.p. administration of desferal to evaluate its effects on asbestos‐induced peritoneal inflammation and iron deposition, as well as oxidative stress. Nitrilotriacetate was used to promote an iron‐catalyzed Fenton reaction as a positive control. Desferal significantly decreased peritoneal fibrosis, iron deposition, and nuclear 8‐hydroxy‐2′‐deoxyguanosine levels in mesothelial cells, whereas nitrilotriacetate significantly increased all of them. Desferal was more effective in rat peritoneal mesothelial cells to counteract asbestos‐induced cytotoxicity than in murine macrophages (RAW264.7). Furthermore, rat sarcomatoid mesothelioma cells were more dependent on iron for proliferation than rat peritoneal mesothelial cells. Because inflammogenicity of a fiber is proportionally associated with subsequent mesothelial carcinogenesis, iron elimination from the mesothelial environment can confer dual merits for preventing asbestos‐induced mesothelial carcinogenesis by suppressing inflammation and mesothelial proliferation simultaneously.
Prognosis of metastatic renal cell carcinoma with first‐line interferon‐α therapy in the era of molecular‐targeted therapy
Authors: Kawano Yoshiaki , Takahashi Wataru , Eto Masatoshi , Kamba Tomomi , Miyake Hideaki , Fujisawa Masato , Kamai Takao , Uemura Hirotsugu , Tsukamoto Taiji , Azuma Haruhito , Matsubara Akio , Nishimura Kazuo , Nakamura Tsuyoshi , Ogawa Osamu , Naito Seiji
Published: April 2016

The RCC‐SELECT study showed the correlation between single nucleotide polymorphisms (SNP) in STAT3 gene and survival in metastatic renal cell carcinoma (mRCC) patients with first‐line interferon‐α (IFN‐α). In that study, even patients with STAT3 SNP linked to shorter overall survival (OS) exhibited remarkably improved prognosis. All 180 patients evaluated in the above study were further analyzed for correlation between OS and demographics/clinicopathological parameters. OS was estimated using the Kaplan–Meier method. Associations between OS and potential prognostic factors were assessed using the log‐rank test and the Cox proportional hazards model. The median OS was 42.8 months. Univariate analysis showed that worse Eastern Cooperative Oncology Group‐performance status (ECOG‐PS), high T stage, regional lymph node metastasis, distant metastasis, higher grade, infiltrative growth pattern, the presence of microscopic vascular invasion (MVI), hypercalcemia, anemia, thrombocytopenia and elevated C‐reactive protein were significantly associated with OS. Multivariate analysis revealed that ECOG‐PS (hazard ratio [HR] = 3.665, P = 0.0004), hypercalcemia (HR = 6.428, P = 0.0005) and the presence of MVI (HR = 2.668, P = 0.0109) were jointly significant poor prognostic factors. This is the first study analysing prognostic factors of mRCC patients with first‐line IFN‐α using large cohort of the prospective study. The present study suggests that first‐line IFN‐α is still a useful therapy for mRCC even in the era of molecular targeted therapy.
Effects of gender, age and menopausal status on serum apolipoprotein concentrations
Authors: Anagnostis Panagiotis , Stevenson John C. , Crook David , Johnston Desmond G. , Godsland Ian F.
Published: April 2016

Objective

To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status.

Design

Cross‐sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins.

Participants

Apparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307).

Measurements

Serum apolipoprotein (apo) B, A‐I and A‐II concentrations were measured, plus serum total cholesterol, low‐density and high‐density lipoprotein cholesterol (LDL‐C and HDL‐C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA‐I, LDL‐C/apoB, HDL‐C/apoA‐I and HDL‐C/apoA‐II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5‐year age ranges.

Results

Overall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50–55 years, with concentrations in men. The LDL‐C/apoB ratio was generally higher in women than in men. ApoA‐I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA‐II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL‐C/apoA‐I and HDL‐C/apoA‐II ratios approaching the lowest ratios, which were seen in men.

Conclusions

Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.
An Asian perspective on improving outcomes for nasal bone fractures by establishing specific treatment options
Authors: Yi J.S. , Kim M.J. , Jang Y.J.
Published: April 2016

Objective

To report treatment outcomes of patients with different types of nasal bone fracture, following a tailored treatment protocol.

Design

The patterns and the severity of the fractures were determined by a preoperative facial photo and nasal bone computed tomography (CT) retrospectively.

Setting

A tertiary referral centre.

Participants

We evaluated 129 patients who underwent surgery between March 2002 and January 2014. Patients were subjected to five different treatment methods depending on the severity of injury.

Main outcome measures

Medical records were reviewed to assess rates of complications and revision surgery. Cosmetic and functional (the degree of nasal obstruction) outcomes were measured using the Likert scale from 1 (very dissatisfied, severe obstruction) to 5 (very satisfied, no obstruction).

Results

The mean elapsed time from injury to surgery was 14.9 days. The overall treatment failure rate, defined as a deformity that required revision, was 6.2%. The patient satisfaction scores for aesthetic and functional outcomes were 3.9 and 4.6 respectively.

Conclusion

The prudent selection of patients with indication for closed reduction, and further specification of variable treatment options for the various degrees of nasal bone fracture, may be helpful in achieving an improved treatment outcome.Level of evidence: level IV.
Management of pouch dysfunction in a tertiary centre
Authors: Ourô S. , Thava B. , Shaikh I. , Clark S. K.
Published: April 2016

Aim

Restorative proctocolectomy (RPC) with ileal pouch–anal anastomosis is the operation of choice for ulcerative colitis (UC) and some cases of familial adenomatous polyposis (FAP). Although it offers improvement in quality of life and high patient satisfaction, pouch surgery is also associated with significant morbidity. The aim of this study was to describe the management of patients referred to a tertiary centre with pouch dysfunction.

Method

All patients referred with pouch dysfunction from other institutions between October 2006 and November 2014 were included in this retrospective study. Information regarding initial diagnosis before RPC, type of procedure, symptoms leading to referral, relation of the appearance of symptoms to the ileostomy closure, investigations, final diagnosis, treatment and follow‐up was reviewed.

Results

One hundred and twenty‐one patients were included, having had RPC mostly for UC (94%), and with diverting ileostomy (83%). The most frequent reasons for referral were high frequency of defaecation in 83 (69%) patients, abdominal pain and incontinence in 45 (37%) each and perianal pain in 44 (36%). The principal investigations performed were pouchoscopy in 97 (80%) patients, examination under anaesthesia (EUA) in 62 (51%), pelvic magnetic resonance imaging (MRI) in 56 (46%) and contrast radiology of the pouch (pouchogram) in 45 (35%). The commonest diagnoses were pouchitis (primary and secondary) in 24 (21%) patients and anastomotic leakage in 26 (22%). After full investigation a cause for the symptoms could not be found in 24 (20%) patients, resulting in the diagnosis of exclusion of ‘irritable pouch syndrome’ or functional disorder. The treatments given were long‐term antibiotic therapy in 29 (25%) patients, ileostomy in 19 (16%), use of a Medena catheter to promote anal evacuation in 17 (15%) and dilatation of a stenosis under anaesthetic in 12 (10%). Six (5%) patients underwent major revision surgery of the pouch with a defunctioning ileostomy and the pouch was excised in another six (5%).

Conclusion

Patients with ileoanal pouch dysfunction often have multiple symptoms. This study shows that a wide range of investigations and treatment modalities need to be available to manage such patients, with a specialized approach in a multidisciplinary setting.
Inflammatory myofibroblastic tumour: a diagnostic challenge on fine needle aspiration cytology
Authors: Sharma S. , Gupta N. , Rajwanshi A. , Saikia U. N.
Published: April 2016

The authors present four cases highlighting the cytological features and differential diagnosis of a rare and enigmatic neoplasm.
Development and reliability of the Functional Communication Classification System for children with cerebral palsy
Authors: Barty Elizabeth , Caynes Katy , Johnston Leanne M
Published: April 2016

Aim

This paper describes the development, validation, and reliability of the Functional Communication Classification System (FCCS), designed to classify expressive communication skills of children with cerebral palsy (CP) aged 4 years and 5 years (between their fourth and sixth birthdays).

Method

The Functional Communication Classification System (FCCS) was developed in 2006 using a literature review, client file audit, and expert consultative committee process in order to devise scale content, structure, and check clinical validity and utility. Interrater reliability was examined between speech–language pathologists (SLPs), other allied health professionals (AHPs), and parents of 48 children with CP. The scale was revised and a clinical reasoning prompt sheet added, then trialled again for 42 children. The result was a five‐level system with descriptors and decision‐making guides for classification of functional expressive communication for children with CP.

Results

Overall interrater reliability was excellent for the final FCCS, intraclass correlation coefficient=0.97 (95% confidence interval 0.95 to 0.98). Kappa values were 0.94 between SLPs and AHPs, 0.59 between SLPs and parents, and 0.60 between AHPs and parents.

Interpretation

The FCCS is a reliable tool for describing functional communication in young children with CP, appropriate for use by SLPs, other AHPs, and parents of children with CP.
Examining factors associated with excess mortality in older people (age ≥ 70 years) with diabetes – a 10‐year cohort study of older people with and without diabetes
Authors: Forbes A. , Murrells T. , Sinclair A. J.
Published: April 2016

Aims

To compare all‐cause mortality in older people with or without diabetes and consider the associated risk of comorbidity and polypharmacy.

Methods

A 10‐year cohort study using data from the Health Innovation Network database (2003–2013) comparing mortality in people aged ≥ 70 years with diabetes (DM cohort) (n = 35 717) and without diabetes (No DM cohort) (n = 307 918).

Results

The mean age of the DM cohort was 78.1 ± 5.8 years vs. 79.0 ± 6.3 years in the No DM cohort. Mean diabetes duration was 8.2 ± 8.1 years, and 30% had diabetes for > 10 years. The DM cohort had a greater comorbidity load and people in this cohort were prescribed more therapies than the No DM cohort. The 5‐ and 10‐year survival rates were lower in the DM cohort at 64% and 39%, respectively, compared with 72% and 50% in the No DM cohort. The excess mortality in the DM cohort was greatest in those aged < 75 years with longer duration diabetes, the relative hazard for mortality was higher in females. Although comorbidity and polypharmacy were associated with increased mortality risk in the DM cohort, this risk was lower compared with the No DM cohort. The hazard ratios (95% confidence interval) for comorbidities > 4 and medicines ≥ 7 were 1.29 (1.19 to 1.41) and 1.34 (1.25 to 1.43) in the DM cohort and 1.63 (1.57 to 1.70) and 1.48 (1.40 to 1.56) in the No DM cohort, respectively.

Conclusions

There is significant excess mortality in older people with diabetes, which is unexplained by comorbidity or polypharmacy. This excess is greatest in the younger old with longer disease duration, suggesting that it may be related to the effect of diabetes exposure.
Disclosure of Type 1 diabetes at work among Finnish workers
Authors: Hakkarainen P. , Moilanen L. , Hänninen V. , Räsänen K. , Munir F.
Published: April 2016

Aims

To determine which self‐management factors and psychosocial work factors were associated with disclosing diabetes to colleagues, line managers and occupational health personnel among workers with Type 1 diabetes.

Methods

A total of 767 working‐aged respondents with Type 1 diabetes completed a Finnish cross‐sectional survey named ‘People with Type 1 Diabetes in Worklife’. Factor analysis was carried out, followed by logistic regressions to estimate the associations between self‐management factors, psychosocial work factors and the likelihood of disclosure separately to colleagues, line managers and occupational health personnel. The models were adjusted for sociodemographic, diabetes‐related and work‐related variables.

Results

A total of 52% of the respondents had disclosed their diabetes to their colleagues, 45% to occupational health personnel and 28% to their line manager. Receiving social support and having good psychosocial work ability were significantly associated with disclosure to colleagues, line managers and occupational health personnel. Relations at work were associated with disclosure to colleagues and the line manager. Furthermore, opportunity to self‐manage diabetes at work was associated with disclosure to colleagues.

Conclusions

Line managers and colleagues have a remarkable role to play in providing workplace support to workers with Type 1 diabetes. Disclosure of Type 1 diabetes should be encouraged as line managers can provide workers with the right support, implement work adaptations and facilitate job retention. As only half of respondents disclosed their Type 1 diabetes at work, further research is required into the reasons for and consequences of not disclosing a diagnosis.
Correlates of psychological outcomes among family members of people with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2™) study
Authors: Kovacs Burns K. , Holt R. I. G. , Nicolucci A. , Lucisano G. , Skovlund S. E. , Comaschi M. , Vallis M. , Peyrot M.
Published: April 2016

Aims

To conduct a second Diabetes Attitudes, Wishes and Needs (DAWN2™) study, examining the experiences of family members caring for adults with diabetes in order to identify correlates of family member psychological outcomes (generic psychological well‐being, perceived quality of life, and diabetes‐related burden, impact and distress).

Methods

A total of 2057 family members living with a person with diabetes and involved in their care participated in an online, telephone or in‐person survey. Samples of 120 respondents were recruited in each of 17 countries. Significant (P < 0.05) correlates of psychological outcomes were identified by multi‐level multiple regression.

Results

Outcomes were worse for family members not working because of diabetes or those who had other competing obligations. Outcomes were worse if the person with diabetes was not a partner or parent, used injected diabetes medication, or had more frequent hypoglycaemia. Outcomes were worse for family members who believed that diabetes was more severe, were more involved in diabetes care, had more conflict over diabetes care or were frustrated about not knowing how to help the person with diabetes. Outcomes were better for those who had greater support from others and felt they found good ways to help the person with diabetes. There were significant differences in outcomes among countries before and after adjustment for individual characteristics, and correlates of outcomes varied by country.

Conclusions

Several modifiable risk and protective factors for family member psychological outcomes were identified in this study. Diabetes education and social support were associated with improved outcomes, especially if they were helpful in supporting people with diabetes.
Localized insulin amyloidosis with use of concentrated insulin: a potential complication
Authors: Mangla A. , Kim G. J. , Agarwal N. , Khurana S. , Catchatourian R. , Jiang J. J.
Published: April 2016

Background

Insulin‐derived amyloidosis is a rare form of amyloidosis composed of insulin fibrils. The pH and concentration of insulin are known to influence the conformational state of the insulin hormone, with an increasing concentration favouring a more complex conformation. Concentrated insulin delivers a large amount of insulin to a localized area, raising the possibility of inducing conformational changes, forming insulin fibrils and leading to localized insulin amyloidosis.

Case report

A middle‐aged woman with long history of Type 2 diabetes mellitus, treated with concentrated human insulin (U‐500 insulin) presented with nodular lesions at the site of her daily insulin injections. A punch biopsy of the nodules showed skin with dermal amyloidosis staining favourably with Congo Red stain. The amyloid tumours were resected and areas positive for Congo Red stain were sent for liquid chromatography tandem mass spectrometry, which showed a peptide profile consistent with amyloid insulin.

Conclusion

Concentrated insulin was first introduced in 1952, however, it is only over the last two decades that it has been used increasingly, in congruence with the increasing incidence of obesity and diabetes mellitus seen in the USA. Only a few cases of insulin amyloidosis at the site of injection have been described in literature. With the increase in the use of insulin, this complication seems to be occurring more frequently. This is the first case report of a person with diabetes mellitus who developed localized insulin amyloidosis with the use of concentrated insulin, and points towards a potential complication of developing insulin amyloidosis with the use of concentrated insulin.
Spacey Parents and Spacey Hosts in Foreign Direct Investment
Authors: Badinger Harald , Egger Peter
Published: April 2016

Shocks on FDI of some parent country in a host affect the same parent's FDI in other hosts. Shocks on a parent's FDI in some host affect other parents' FDI in the same host. In general equilibrium, shocks on FDI between any country pair will affect all country pairs' FDI. Using cross‐sectional data on FDI among 22 OECD countries in 2000, we use a spatial estimation framework to allow for all three modes of interdependence simultaneously, thereby distinguishing between market‐size‐related and remainder interdependence. Our results highlight the complexity of multinational enterprises' investment strategies and the interconnectedness of the world investment system.
Do self‐efficacy and depression predict oral impacts on daily performances across time? A 2‐yr follow‐up of students in Tanzania
Authors: Åstrøm Anne N. , Lie Stein A. , Mbawalla Hawa
Published: April 2016

This study aimed to assess the longitudinal validity of the oral impacts on daily performance (OIDP) and to identify psychosocial determinants, in terms of self‐efficacy and depressive symptoms, of theOIDPacross time. Following conceptual frameworks of oral health, it was hypothesized that sociodemographic, clinical, and psychosocial factors predict oral impacts across time at both population‐ averaged and person‐specific levels. Whether the effects of sociodemographic and clinical factors were accounted for, totally or in part, by psychosocial factors were also investigated. Self administered questionnaires and oral clinical examinations at baseline (2009) and follow‐up (2011) were completed by 1,714 and 727 secondary school students, respectively. Generalized equalized equations and a random intercept model were used to account for the dependency in repeated observations. MeanOIDPchange scores were negative (worsened) among those who reported worsened self‐reported oral health. Psychosocial, clinical, and sociodemographic factors were independently associated with oral impacts at the population‐averaged and person‐specific levels. Mediation of sociodemographic and clinical variables according to psychosocial variables was not observed. Satisfactory longitudinal evaluative properties of theOIDP, and independent effects of psychosocial factors on oral impacts across time, were confirmed among secondary school students in Tanzania.
Resilience to What? Resilience for Whom?
Authors: Cutter Susan L
Published: April 2016

The discourse on disaster resilience and vulnerability entails diverse research and policy communities each assigning different meanings to the concepts, which in turn influences their measurement and implementation in decision‐making contexts. This invited contribution introduces a themed section with five independently submitted papers on the broad topic of vulnerability and resilience. The distinctive geographical focus on the historical development of vulnerability and resilience and their contemporary manifestations is illustrated by the five internationally focused case studies presented in the themed section.
Patient involvement in the development of a handbook for moderate rheumatoid arthritis
Authors: Prothero Louise , Georgopoulou Sofia , de Souza Savia , Bosworth Ailsa , Bearne Lindsay , Lempp Heidi
Published: April 2016

Background

Self‐management is a key recommendation for people with rheumatoid arthritis (RA). Educational materials may support self‐management, and increasingly patients are becoming involved with the development of these materials. The TITRATE trial compares the effectiveness of intensive management to standard care in patients with moderate RA across England. As part of the intensive management intervention, participants are given a handbook.

Aim and objectives

The aim of this study was to develop a handbook to support the intensive management. The objectives were to: (i) involve patients in the identification of relevant information for inclusion in the TITRATE handbook; (ii) ensure the content of the handbook is acceptable and accessible.

Design

We held an audio‐taped workshop with RA patients. The transcript of the workshop was analysed using thematic content analysis.

Results

Five main themes were identified as follows: ‘rheumatoid arthritis treatment, perceptions of rheumatoid arthritis, the importance of individualized goals, benefits of self‐management and the patient handbook’. Feedback from the workshop was incorporated into the handbook, and patients’ anonymous testimonies were added.

Conclusion

This study demonstrates that patient contribution to the development of educational material to support intensive management of RA is both feasible and valuable. A qualitative evaluation of the use and impact of the handbook with patients and practitioners is planned on completion of the TITRATE trial.
Lymph node – an organ for T‐cell activation and pathogen defense
Authors: Gasteiger Georg , Ataide Marco , Kastenmüller Wolfgang
Published: April 2016

The immune system is a multicentered organ that is characterized by intimate interactions between its cellular components to efficiently ward off invading pathogens. A key constituent of this organ system is the distinct migratory activity of its cellular elements. The lymph node represents a pivotal meeting point of immune cells where adaptive immunity is induced and regulated. Additionally, besides barrier tissues, the lymph node is a critical organ where invading pathogens need to be eliminated in order to prevent systemic distribution of virulent microbes. Here, we explain how the lymph node is structurally and functionally organized to fulfill these two critical functions – pathogen defense and orchestration of adaptive immunity. We will discuss spatio‐temporal aspects of cellular immune responses focusing on CD8 T cells and review how and where these cells are activated in the context of viral infections, as well as how viral antigen expression kinetics and different antigen presentation pathways are involved. Finally, we will describe how such responses are regulated and ‘helped’, and discuss how this relates to intranodal positioning and cellular migration of the various cellular components that are involved in these processes.
Tertiary lymphoid structures, drivers of the anti‐tumor responses in human cancers
Authors: Dieu‐Nosjean Marie‐Caroline , Giraldo Nicolas A. , Kaplon Hélène , Germain Claire , Fridman Wolf Herman , Sautès‐Fridman Catherine
Published: April 2016

The characterization of the microenvironment of human tumors led to the description of tertiary lymphoid structures (TLS) characterized by mature dendritic cells in a T‐cell zone adjacent to B‐cell follicle including a germinal center. TLS represent sites of lymphoid neogenesis that develop in most solid cancers. Analysis of the current literature shows that the TLS presence is associated with a favorable clinical outcome for cancer patients, regardless of the approach used to quantify TLS and the stage of the disease. Using several approaches that combine immunohistochemistry, gene expression assays, and flow cytometry on large series of lung tumors, our work demonstrated that TLS are important sites for the initiation and/or maintenance of the local and systemic T‐ and B‐cell responses against tumors. Surrounded by high endothelial venules, they represent a privileged area for the recruitment of lymphocytes into tumors and generation of central‐memory T and B cells that circulate and limit cancer progression. TLS can be considered as a novel biomarker to stratify the overall survival risk of untreated cancer patients and as a marker of efficient immunotherapies. The induction and manipulation of cancer‐associated TLS using drug agonists and/or biotherapies should open new avenues to treat cancer patients.
Control of the thymic medulla and its influence on αβT‐cell development
Authors: Lucas Beth , McCarthy Nicholas I. , Baik Song , Cosway Emilie , James Kieran D. , Parnell Sonia M. , White Andrea J. , Jenkinson William E. , Anderson Graham
Published: April 2016

The thymus is a primary lymphoid tissue that supports the generation of αβT cells. In this review, we describe the processes that give rise to the thymus medulla, a site that nurtures self‐tolerant T‐cell generation following positive selection events that take place in the cortex. To summarize the developmental pathways that generate medullary thymic epithelial cells (mTEC) from their immature progenitors, we describe work on both the initial emergence of the medulla during embryogenesis, and the maintenance of the medulla during postnatal stages. We also investigate the varying roles that receptors belonging to the tumor necrosis factor receptor superfamily have on thymus medulla development and formation, and highlight the impact that T‐cell development has on thymus medulla formation. Finally, we examine the evidence that the thymic medulla plays an important role during the intrathymic generation of distinct αβT‐cell subtypes. Collectively, these studies provide new insight into the development and functional importance of medullary microenvironments during self‐tolerant T‐cell production in the thymus.
Thymocytes self‐renewal: a major hope or a major threat?
Authors: Peaudecerf Laetitia , Krenn Gerald , Gonçalves Pedro , Vasseur Florence , Rocha Benedita
Published: April 2016

Thymus transplants were never used to correct T‐cell intrinsic deficiencies, as it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on multiple thymus transplantation experiments, where it was shown that thymus‐resident cells were rapidly replaced by progenitors migrating from the bone marrow (BM). This substitution occurs even when bone marrow precursors are unable to generate T cells, as in Rag1/2− or severe combined immunodeficiency (SCID)‐deficient mice. In contrast, two groups reported that neonatal thymi transplanted into mice that cannot respond to IL‐7 harbor populations with extensive capacity to self‐renew, which maintain continuous thymocyte generation for several months after surgery. The consequences of this self‐renewal capacity differed in these two laboratories. We found that these thymus transplants rapidly reconstitute the full diversity of peripheral T‐cell repertoires 1 month after surgery, the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic‐transplanted thymi are not rejected, and allogeneic cells do not induce graft‐versus‐host disease, both syngeneic and allogeneic transplants inducing rapid protection from infection. These results indicate a potential use of neonatal thymus transplants to correct T‐cell intrinsic deficiencies. The other group observed that continuous thymocyte renewal from BM precursors was fundamental to prevent tumor development. In the absence of this input, thymocytes from the transplanted thymus generated tumors with all the characteristics of T‐cell acute lymphoblastic leukemia (T‐ALL). Moreover, they suggested that the absence of BM competition was responsible for the T‐ALLs developing in X‐linked severe combined immunodeficiency (SCID)‐X1 patients, deficient in the expression of IL2‐Rγc. These patients were treated with autologous CD34+ cells transfected with virus vectors expressing γc in the absence of myeloablation. We here review the potential therapeutic impact of thymus transplantation and compare the results of these two laboratories aiming to find an answer to the ‘Dr Jekill versus Mr. Hyde’ status of thymus transplantation experiments.
Dendritic cells in remodeling of lymph nodes during immune responses
Authors: Acton Sophie E. , Reis e Sousa Caetano
Published: April 2016

A critical hallmark of adaptive immune responses is the rapid and extensive expansion of lymph nodes. During this process, the complex internal structure of the organs is maintained revealing the existence of mechanisms able to balance lymph node integrity with structural flexibility. This article reviews the extensive architectural remodeling that occurs within lymph nodes during adaptive immune responses and how it is regulated by dendritic cells (DCs). In particular we focus on previously unappreciated functions of DCs in coordinating remodeling of lymph node vasculature, expansion of the fibroblastic reticular network and maintenance of lymphoid stromal phenotypes. Our increased understanding of these processes indicates that DCs need to be viewed not only as key antigen‐presenting cells for lymphocytes but also as broad‐acting immune sentinels that convey signals to lymphoid organ stroma and thereby facilitate immune response initiation at multiple levels.
Autoimmune regulator and self‐tolerance – molecular and clinical aspects
Authors: Abramson Jakub , Husebye Eystein S.
Published: April 2016

The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type‐1 (APS‐1), is crucial for the establishment of self‐tolerance in the thymus by promoting promiscuous expression of a wide array of tissue‐restricted self‐antigens. This step is critical for elimination of high‐affinity self‐reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3+ T‐regulatory (Treg) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self‐tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.
Information systems absorptive capacity for environmentally driven IS‐enabled transformation
Authors: Cooper Vanessa , Molla Alemayehu
Published: April 2016

The potential of information systems (IS) to enable environmental sustainability necessitates an understanding of how organisations can realise this potential. In this study, building on the absorptive capacity theory and following a multi‐disciplinary and multi‐method approach, we propose that developing IS‐environmental absorptive capacity is a significant mechanism to deliver IS‐enabled change that addresses environmental issues. We commenced with a literature review and exploratory interviews to define the IS‐environmental absorptive capacity construct. We then developed a model that proposes that sustainable IS triggers, knowledge exposure and prior experience influence IS‐environmental absorptive capacity, which in turn contributes to the level of environmentally sustainable IS assimilation as well as to the cost saving, operational performance and reputation of organisations. The model was first tested through an international survey of 148 senior IS managers. The findings support our model regarding the antecedents and value of IS‐environmental absorptive capacity. A follow‐up case study corroborated the survey results and provided additional insights into the nature and causes of IS‐environmental absorptive capacity and its value. This study, in addition to presenting empirical evidence, defines and operationalises the IS‐environmental absorptive capacity construct in a theoretically and operationally meaningful way.
Relationship between calving difficulty and fertility traits in first‐parity Iranian Holsteins under standard and recursive models
Authors: Mokhtari M.S. , Moradi Shahrbabak M. , Nejati Javaremi A. , Rosa G.J.M.
Published: April 2016

The main objective of this study was to estimate the genetic and phenotypic relationships between calving difficulty (CD) and fertility traits, including success at first service (SF), number of inseminations to conception (INS), interval from calving to first service (CTFS), interval between first and last service (IFL) and days open (DO), in first‐parity Iranian Holsteins under standard (SMMs) and recursive (RMMs) mixed models. The data analysed in this paper included 29 950 records on CD and fertility traits, collected in the time period from 1995 to 2014 by the Animal Breeding and Improvement Center of Iran. Under all observed SMMs and RMMs, five bivariate sire‐maternal grandsire models (ten bivariate analyses in total) were used for the analyses. Recursive models were applied with a view to consider that CD influences the fertility traits in the subsequent reproductive cycle and the genetic determination of CD and fertility traits by fitting CD as covariate for any of the fertility traits studied. The existence of such cause‐and‐effect is considered in RMMs but not in SMMs. Our results implied a statistically non‐zero magnitude of the causal relationships between CD and all the fertility traits studied, with the former influencing the latter. The causal effects of CD on SF (on the observed scale, %), INS, CTFS, IFL and DO were −2.23%, 0.10 services, 1.93 days, 3.76 days and 5.61 days, respectively. Direct genetic correlations between CD and the fertility traits under both models were not statistically different from zero (95% HPD interval included zero), except for the correlation between CD and CTFS, which were 0.197 and 0.134 under SMM and RMM, respectively, indicating that genes associated with difficult births also increase intervals between calving and the first insemination afterwards. Comparison of both models by the deviance information criterion (DIC) demonstrated the plausibility of RMMs over SMMs.
Accuracy of genomic prediction of purebreds for cross bred performance in pigs
Authors: Hidalgo A.M. , Bastiaansen J.W.M. , Lopes M.S. , Calus M.P.L. , de Koning D.J.
Published: April 2016

In pig breeding, as the final product is a cross bred (CB) animal, the goal is to increase the CB performance. This goal requires different strategies for the implementation of genomic selection from what is currently implemented in, for example dairy cattle breeding. A good strategy is to estimate marker effects on the basis of CB performance and subsequently use them to select pure bred (PB) breeding animals. The objective of our study was to assess empirically the predictive ability (accuracy) of direct genomic values of PB for CB performance across two traits using CB and PB genomic and phenotypic data. We studied three scenarios in which genetic merit was predicted within each population, and four scenarios where PB genetic merit for CB performance was predicted based on either CB or a PB training data. Accuracy of prediction of PB genetic merit for CB performance based on CB training data ranged from 0.23 to 0.27 for gestation length (GLE), whereas it ranged from 0.11 to 0.22 for total number of piglets born (TNB). When based on PB training data, it ranged from 0.35 to 0.55 for GLE and from 0.30 to 0.40 for TNB. Our results showed that it is possible to predict PB genetic merit for CB performance using CB training data, but predictive ability was lower than training using PB training data. This result is mainly due to the structure of our data, which had small‐to‐moderate size of the CB training data set, low relationship between the CB training and the PB validation populations, and a high genetic correlation (0.94 for GLE and 0.90 for TNB) between the studied traits in PB and CB individuals, thus favouring selection on the basis of PB data.