bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing long‐term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy
Authors: Moschini Marco , Sharma Vidit , Dell'oglio Paolo , Cucchiara Vito , Gandaglia Giorgio , Cantiello Francesco , Zattoni Fabio , Pellucchi Federico , Briganti Alberto , Damiano Rocco , Montorsi Francesco , Salonia Andrea , Colombo Renzo
Published: April 2015

Objective

To assess the impact of primary or progressive status on recurrence‐free survival (RFS), cancer‐specific mortality (CSM) and overall mortality (OM) after radical cystectomy (RC) for muscle‐ invasive bladder cancer (MIBC).

Patients and Methods

A total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non‐MIBC (NMIBC) that had progressed to MIBC. The median follow‐up was 85 (60–109) months. Univariate and multivariate Cox regression models were used to compare RFS, CSM and OM between these two cohorts.

Results

In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC. There were no differences between the two groups in terms of demographics, pathological and peri‐operative complications (all P > 0.1). The 10‐year RFS, CSM and OM rates for primary vs progressive status were 43 vs 36% (P = 0.01), 43 vs 37% (P = 0.01), and 35 vs 28% (P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.12–1.79; P = 0.03), CSM (HR 1.42, 95% CI 1.07–1.89; P = 0.01) and OM (HR1.42, 95% CI 1.13–1.65; P = 0.02).

Conclusions

Among patients treated with RC for MIBC, progressive status was associated with a higher CSM, OM and recurrence rate after RC. The present study thus provides an impetus to improve risk sub‐stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC.
Expression of ribosome‐binding protein 1 correlates with shorter survival in Her‐2 positive breast cancer
Authors: Liang Xiaoshuan , Sun Shanshan , Zhang Xianyu , Wu Hao , Tao Weiyang , Liu Tong , Wei Wei , Geng Jingshu , Pang Da
Published: April 2015

The aim of this study is to investigate the expression of ribosome‐binding protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied using real‐time quantitative PCR and western blotting using pair‐matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P = 0.02), molecular subtype (P = 0.048) and status of Her‐2 (P = 0.026) and P53 (P = 0.015). We performed a grade‐stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected overall survival in patients with early‐stage (I and II) tumors (P = 0.042). Furthermore, Her‐2 positive patients with negative RRBP1 expression had longer overall survival rates than those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a valuable prognostic factor in Her‐2‐positive breast cancer patients, indicating that RRBP1 is a potentially important target for the prediction of prognosis.
Clinical correlates of human leucocyte antigen (HLA)-G in systemic sclerosis
Authors: Favoino E , Favia I E , Vettori S , Vicenti C , Prete M , Valentini G , Perosa F
Published: April 2015

Human leucocyte antigen (HLA)-G has a tolerogenic function and could play a role in the pathogenesis of immune-mediated diseases, including systemic sclerosis (SSc). The aim of this study was to evaluate HLA-G serum expression (sHLA-G) and the HLA-G gene 14 base pairs (bp) insertion/deletion (del−/del+) polymorphism in patients with Ssc, to search for possible associations with clinical and laboratory variables. sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA) in sera from 77 patients with SSc and 32 healthy donors (HD); the 14 bp del−/del+ polymorphism was evaluated by polymerase chain reaction (PCR) amplification of peripheral blood mononuclear cells (PBMC) genomic DNA. Receiver operating characteristics (ROC) analysis identified the HLA-G cut-off that best discriminated dichotomized clinical and serological variables, that was subsequently employed to subdivide SSc patients into HLA-G high (HLA-G+) and low (HLA-G−) profile groups. sHLA-G were not statistically different between SSc patients and HD, nor between distinct SSc autoantibody subsets. Subdividing SSc patients by HLA-G positivity or negativity yielded significant differences for the modified Rodnan skin score (mRss) (P = 0·032), ‘general’ (P = 0·031) and ‘kidney’ (P = 0·028) Medsger severity scores (MSS) and disease activity index, and especially Δ heart/lung (P = 0·005). A worse ‘general’ MSS (P = 0·002) and Δ heart/lung (P = 0·011) were more frequent in the low sHLA-G group. These two variables and mRss were associated with sHLA-G levels at logistic regression analysis. Treatment had no influence on sHLA-G. Moreover, a higher frequency of scleredema was detected in the del+/del+ than the del-/del+ group (P = 0.04). These data suggest modulatory effects of sHLA-G on SSc. Prospective studies are needed to investigate a role in predicting the disease course.
Prime-boost vaccination strategy with bacillus Calmette–Guérin (BCG) and liposomized alpha-crystalline protein 1 reinvigorates BCG potency
Authors: Siddiqui K F , Amir M , Khan N , Rama Krishna G , Sheikh J A , Rajagopal K , Agrewala J N
Published: April 2015

Bacillus Calmette–Guérin (BCG) remains the only available and most widely administered vaccine against Mycobacterium tuberculosis (Mtb), yet it fails to protect vaccinated individuals either from primary infection or reactivation of latent tuberculosis (TB). Despite BCG's variable efficacy against TB, the fact remains that BCG imparts protection in children against the disease, indicating that BCG possesses a wide protective antigenic repertoire. However, its failure to impart protection in adulthood can be linked to its failure to generate long-lived memory response and elicitation of an inadequate immune response against latency-associated antigens. Therefore, to improve the protective efficacy of BCG, a novel vaccination strategy is required. Consequently, in the present study, we have exploited the vaccination potential of liposomized α-crystalline 1 (Acr1L), a latency-associated antigen to induce enduring protective immunity against Mtb in BCG-primed animals. It is noteworthy that an increase in the multi-functional [interferon (IFN)-γhi/tumour necrosis factor (TNF)-αhi] CD4 and CD8 T cells were observed in BCG-primed and Acr1L-boosted (BCG-Acr1L) animals, compared to BCG alone. Further, substantial expansion of both central memory (CD44hi/CD62Lhi) and effector memory (CD44hi/CD62Llo) populations of CD4 and CD8 T cells was noted. Importantly, BCG-Acr1L exhibited significantly better protection than BCG, as evidenced by a reduction in the bacterial burden and histopathological data of the lungs. In essence, BCG-Acr1L could be a potent future vaccination strategy to reinvigorate BCG potency.
Increased lymphocyte apoptosis in mouse models of colitis upon ABT-737 treatment is dependent upon BIM expression
Authors: Lutz C , Mozaffari M , Tosevski V , Caj M , Cippà P , McRae B L , Graff C L , Rogler G , Fried M , Hausmann M
Published: April 2015

Exaggerated activation of lymphocytes contributes to the pathogenesis of inflammatory bowel disease (IBD). Medical therapies are linked to the BCL-2 family-mediated apoptosis. Imbalance in BCL-2 family proteins may cause failure in therapeutic responses. We investigated the role of BCL-2 inhibitor ABT-737 for lymphocyte apoptosis in mice under inflammatory conditions. B.6129P2-interleukin (IL)-10tm1Cgn/J (IL-10−/−) weighing 25–30 g with ongoing colitis were used. Fifty mg/kg/day ABT-737 was injected intraperitoneally (i.p.). Haematological analyses were performed with an ADVIA 2120 flow cytometer and mass cytometry with a CyTOF 2. Following i.p. administration, ABT-737 was detected in both spontaneous and acute colitis in peripheral blood (PBL) and colon tissue. Treatment led to lymphopenia. CD4+CD44+CD62L+ central memory and CD8+, CD44+ CD62L− central memory T cells were decreased in PBL upon ABT-737 compared to vehicle-receiving controls. Increased apoptosis upon ABT-737 was determined in blood lymphocytes, splenocytes and Peyer's patches and was accompanied by a decrease in TNF and IL-1B. ABT-737 positively altered the colonic mucosa and ameliorated inflammation, as shown by colonoscopy, histology and colon length. A decreased BIM/BCL-2 ratio or absence of BIM in both Bim−/− and Il10−/− × Bim−/− impeded the protective effect of ABT-737. The BIM/BCL-2 ratio decreased with age and during the course of treatment. Thus, long-term treatment resulted in adapted TNF levels and macroscopic mucosal damage. ABT-737 was efficacious in diminishing lymphocytes and ameliorating colitis in a BIM-dependent manner. Regulation of inappropriate survival of lymphocytes by ABT-737 may provide a therapeutic strategy in IBD.
Immunoglobulin A in serum: an old acquaintance as a new prognostic biomarker in idiopathic pulmonary fibrosis
Authors: ten Klooster L , van Moorsel C H M , Kwakkel-van Erp J M , van Velzen-Blad H , Grutters J C
Published: April 2015

Immunoglobulin (Ig)A is an important immunoglobulin in mucosal immunity and protects the lungs against invading pathogens. The production of IgA is regulated by transforming growth factor (TGF)-β, a versatile cytokine and key player in the pathogenesis of pulmonary fibrosis. TGF-β is up-regulated in patients with idiopathic pulmonary fibrosis (IPF), but difficult to use as a biomarker. The aim of this study was to evaluate the prognostic value of IgA in serum in patients with IPF. We examined IgA levels at time of diagnosis in 86 patients diagnosed with IPF. Mean serum IgA level in IPF is 3·22 g/l and regression analyses showed a significant association with mortality (hazard ratio = 1·445, P = 0·002). A significantly worse survival was found in patients with IgA serum levels > 2·85 g/l compared to patients with lower IgA serum levels (P = 0·003). These findings were confirmed in a duplication cohort. In conclusion, the level of IgA in blood is a promising prognostic marker in IPF and can be implemented easily in the hospital setting. Future studies are warranted to investigate if repeated measurements of serum IgA can further improve the performance of serum IgA as a prognostic marker.
10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers
Authors: Muema D M , Nduati E W , Uyoga M , Bashraheil M , Scott J A G , Hammitt L L , Urban B C
Published: April 2015

Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12–23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3–45%; P < 0·01), 19F (21–66%; P < 0·01) and 23F (13–36%; P = 0·02), but not serotypes 6B (24–42%; P = 0·24) and 14 (21–40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.
Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells
Authors: Katsiougiannis S , Tenta R , Skopouli F N
Published: April 2015

The aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sjögren's syndrome (SS) autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/Sjögren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens.
Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice
Authors: Cai Z , Wong C K , Dong J , Chu M , Jiao D , Kam N W , Lam C W K , Tam L S
Published: April 2015

The immunological mechanisms mediated by regulatory cytokine interleukin (IL)-35 are unclear in systemic lupus erythematosus (SLE). We investigated the frequency of CD4+CD25+forkhead box protein 3 (FoxP3)+ regulatory T (Treg) and IL-10+ regulatory B (Breg) cells and related immunoregulatory mechanisms in a female Murphy Roths Large (MRL)/lpr mouse model of spontaneous lupus-like disease, with or without IL-35 treatment. A remission of histopathology characteristics of lupus flare and nephritis was observed in the MRL/lpr mice upon IL-35 treatment. Accordingly, IL-35 and IL-35 receptor subunits (gp130 and IL-12Rβ2) and cytokines of MRL/lpr and BALB/c mice (normal controls) were measured. The increased anti-inflammatory cytokines and decreased proinflammatory cytokines were possibly associated with the restoration of Treg and Breg frequency in MRL/lpr mice with IL-35 treatment, compared to phosphate-buffered saline (PBS) treatment. mRNA expressions of Treg-related FoxP3, IL-35 subunit (p35 and EBI3) and soluble IL-35 receptor subunit (gp130 and IL12Rβ2) in splenic cells were up-regulated significantly in IL-35-treated mice. Compared with the PBS treatment group, IL-35-treated MRL/lpr mice showed an up-regulation of Treg-related genes and the activation of IL-35-related intracellular Janus kinase/signal transducer and activator of transcription signal pathways, thereby indicating the immunoregulatory role of IL-35 in SLE. These in vivo findings may provide a biochemical basis for further investigation of the regulatory mechanisms of IL-35 for the treatment of autoimmune-mediated inflammation.
Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial
Authors: Israeli E , Goldin E , Fishman S , Konikoff F , Lavy A , Chowers Y , Melzer E , Lahat A , Mahamid M , Shirin H , Nussinson E , Segol O , Ben Ya'acov A , Shabbat Y , Ilan Y
Published: April 2015

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.
Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited
Authors: Wang Weiqing , Wang Shuwei , Jiang Yiran , Yan Fuhua , Su Tingwei , Zhou Weiwei , Jiang Lei , Zhang Yifei , Ning Guang
Published: April 2015

Context

Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings.

Objective

The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS.

Methods

This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared.

Results

Of the 74 patients with PSIS, age at diagnosis was 25 (22–28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin‐releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24‐h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups.

Conclusions

The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.
A systematic review of sacral nerve stimulation for low anterior resection syndrome
Authors: Ramage L. , Qiu S. , Kontovounisios C. , Tekkis P. , Rasheed S. , Tan E.
Published: April 2015

Aim

The efficacy of sacral nerve stimulation (SNS) in low anterior resection syndrome (LARS) is largely undocumented. A review of the literature was carried out to study this question.

Method

Pubmed, Medline and Cochrane databases were searched for relevant articles up to August 2014. Studies were included if they evaluated the use ofSNSfollowing rectal resection and assessed at least one of the following end‐points: bowel function, quality of life and ano‐neorectal physiology. No restrictions on language or study size were made.

Results

Seven papers were identified including one case report and six prospective case series. These included 43 patients with a median follow‐up of 15 months. After peripheral nerve evaluation definitive implantation was carried out in 34 (79.1%) patients. Overall, 32 (94.1%) of the 34 patients experienced improvement of symptoms which, based on intention to treat, was 32/43 (74.4%).

Conclusion

The review suggests thatSNSfor faecal incontinence inLARShas success rates comparable to its use for other forms of faecal incontinence.
Ups and Downs in Auditory Development: Preschoolers’ Sensitivity to Pitch Contour and Timbre
Authors: Creel Sarah C.
Published: April 2015

Much research has explored developing sound representations in language, but less work addresses developing representations of other sound patterns. This study examined preschool children's musical representations using two different tasks: discrimination and sound–picture association. Melodic contour—a musically relevant property—and instrumental timbre, which is (arguably) less musically relevant, were tested. In Experiment 1, children failed to associate cartoon characters to melodies with maximally different pitch contours, with no advantage for melody preexposure. Experiment 2 also used different‐contour melodies and found good discrimination, whereas association was at chance. Experiment 3 replicated Experiment 2, but with a large timbre change instead of a contour change. Here, discrimination and association were both excellent. Preschool‐aged children may have stronger or more durable representations of timbre than contour, particularly in more difficult tasks. Reasons for weaker association of contour than timbre information are discussed, along with implications for auditory development.
The over‐pruning hypothesis of autism
Authors: Thomas Michael S.C. , Davis Rachael , Karmiloff‐Smith Annette , Knowland Victoria C.P. , Charman Tony
Published: April 2015

This article outlines the over‐pruning hypothesis of autism. The hypothesis originates in a neurocomputational model of the regressive sub‐type (Thomas, Knowland & Karmiloff‐Smith, 2011a, 2011b). Here we develop a more general version of the over‐pruning hypothesis to address heterogeneity in the timing of manifestation of ASD, including new computer simulations which reconcile the different observed developmental trajectories (early onset, late onset, regression) via a single underlying atypical mechanism; and which show how unaffected siblings of individuals with ASD may differ from controls either by inheriting a milder version of the pathological mechanism or by co‐inheriting the risk factors without the pathological mechanism. The proposed atypical mechanism involves overly aggressive synaptic pruning in infancy and early childhood, an exaggeration of a normal phase of brain development. We show how the hypothesis generates novel predictions that differ from existing theories of ASD including that (1) the first few months of development in ASD will be indistinguishable from typical, and (2) the earliest atypicalities in ASD will be sensory and motor rather than social. Both predictions gain cautious support from emerging longitudinal studies of infants at‐risk of ASD. We review evidence consistent with the over‐pruning hypothesis, its relation to other current theories (including C. Frith's under‐pruning proposal; C. Frith, 2003, 2004), as well as inconsistent data and current limitations. The hypothesis situates causal accounts of ASD within a framework of protective and risk factors (Newschaffer et al., 2012); clarifies different versions of the broader autism phenotype (i.e. the implication of observed similarities between individuals with autism and their family members); and integrates data from multiple disciplines, including behavioural studies, neuroscience studies, genetics, and intervention studies.
Australian hip surveillance guidelines for children with cerebral palsy: 5‐year review
Authors: Wynter Meredith , Gibson Noula , Willoughby Kate L , Love Sarah , Kentish Megan , Thomason Pam , Graham H Kerr ,   the National Hip Surveillance Working Group
Published: April 2015

Aim

To ensure hip surveillance guidelines reflect current evidence of factors influencing hip displacement in children with cerebral palsy (CP).

Method

A three‐step review process was undertaken: (1) systematic literature review, (2) analysis of hip surveillance databases, and (3) national survey of orthopaedic surgeons managing hip displacement in children with CP.

Results

Fifteen articles were included in the systematic review. Quantitative analysis was not possible. Qualitative review indicated hip surveillance programmes have decreased the incidence of hip dislocation in populations with CP. The Gross Motor Function Classification System was confirmed as the best indicator of risk for displacement, and evidence was found of hip displacement occurring at younger ages and in young adulthood. Femoral geometry, pelvic obliquity, and scoliosis were linked to progression of hip displacement. A combined data pool of 3366 children from Australian hip surveillance databases supported the effectiveness of the 2008 Consensus Statement to identify hip displacement early. The survey of orthopaedic surgeons supported findings of the systematic review and database analyses.

Interpretation

This review rationalized changes to the revised and renamed Australian Hip Surveillance Guidelines for Children with Cerebral Palsy 2014, informing frequency of radiographic examination in lower risk groups and continuation of surveillance into adulthood for adolescents with identified risk factors.
Can feeding–swallowing difficulties in children predict language impairments?
Authors: Lefton‐Greif Maureen A
Published: April 2015

This commentary is on the original article by Malas et al. on pages 872–879 of this issue.
Collaborative Learning Using a Project across Multiple Business Courses: A Cognitive Load and Knowledge Convergence Approach
Authors: Bhowmick Sandeep , Chandra Aruna , Harper Jeffrey S. , Sweetin Vernon
Published: April 2015

Four business professors at a state university in the Midwestern United States launched a collaborative learning project grounded in cognitive learning theory and knowledge convergence theory with the objective of assessing student learning gains in cross‐functional knowledge (CFK), course‐related knowledge (CRK), and overall satisfaction with this teaching approach. The project involved the start‐up and operation of an entrepreneurial campus lunch delivery service from local restaurants to university faculty, students, and staff.

A total of 46 students participated in the project, and comprised seven groups across four business courses: Strategy, Project Management, Marketing Promotion, and Marketing Research. A survey instrument was developed comprising 21 items. Survey results indicated significant increases in cross‐functional and course‐related knowledge, and in student involvement and teamwork when using this cross‐functional, multicourse approach to an entrepreneurial endeavor.
The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens
Authors: Salerni Sara , Di Francescomarino Samanta , Cadeddu Christian , Acquistapace Flavio , Maffei Silvia , Gallina Sabina
Published: April 2015

Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex‐steroid hormones have been postulated as the major contributors towards these sex‐related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex‐steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation–contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart.
Using discussion groups as a strategy for postgraduate implant dentistry students to reflect
Authors: Koole S. , Fine P. , De Bruyn H.
Published: April 2015

Introduction

More than undergraduates, postgraduate students have the day‐to‐day clinical experience to reflect upon. Nevertheless, reflection in postgraduate dental education is less well studied. Hence, the purpose was to investigate the attitude towards reflection and the content of reflections in postgraduate implant dentistry education in the UK and Belgium.

Materials and Methods

To investigate the attitude towards reflection, a questionnaire was administered to the 10 postgraduates at UCL Eastman Dental Institute (EDI) and 6 postgraduates at Ghent University (UGent). Additionally, students were invited to attend two reflective sessions (60‐90 minutes). The sessions’ audio recordings were transcribed and analysed using a thematic approach.

Results

In total, 16 postgraduate implant dentistry students participated. Although the majority reported prior experience with reflection, there was variation in the provided definitions of reflection. EDI students agreed with reflection being beneficial for professional development/clinical reasoning and were positive about discussing clinical experiences in groups, but were divided about individual/group reflections. Their UGent counterparts were more indecisive (=neutral), but were positive about discussing clinical experiences. Thematic analysis identified recurring themes as individual learning process, learning and clinical experiences, attitude towards implant dentistry and course programme. EDI postgraduates’ reflections focussed on specific clinical situations, while UGent postgraduates’ reflections described general considerations.

Conclusion

Although students/professionals often report to reflect, it is not clear whether/how they actually reflect, due to the all‐purpose word reflection has become. A strategy, using group discussions along with supervision/guidance in how to reflect, demonstrated to expand clinical reasoning into reflections about postgraduate students’ clinical actions and professional growth.
Business as Usual? An Institutional View of the Relationship Between Management Control Systems and Strategy
Authors: Tucker Basil P. , Parker Lee D.
Published: April 2015

The relationship between management control systems (MCS) and strategy has received considerable attention in the management control literature. Contingency‐based approaches, however, have traditionally dominated this research, with limited attention devoted specifically to how MCS and strategy may combine in organisations operating within highly institutionalised environments. Adopting an institutional perspective, the current study is based on interviews with CEOs and senior executives in 32 Australian Not‐for‐Profit organisations. Our findings indicate a tendency for these organisations to decouple informal control from MCS, producing a ‘business as usual’ mentality via the pervasive informal approach to control, supplanting contingency‐based predictions relating to MCS‐strategy relations.
The Cascade of Fear: Policy Implementation and Financial Management Reform in the European Commission
Authors: Levy Roger P. , Barzelay Michael , Gomez Antonio‐Martin Porras
Published: April 2015

The complexity of managing European Union (EU) spending programmes is the subject of much comment but relatively little academic analysis. Using a multi‐disciplinary analytical framework drawn from the management, policy and social sciences, this fieldwork‐based case study examines the reform of financial management within the European Commission. In constructing an agent focussed narrative of a specific reform episode, it contributes to a growing literature on public management reform analysed from this perspective and also to the lightly developed field of EU financial management.
The Influence of Management Accounting Departments Within German Municipal Administrations
Authors: Hirsch Bernhard , Nitzl Christian , Schauß Joachim
Published: April 2015

The achievement of better performance from municipal administrations is an ongoing challenge. We use the contingency theory perspective, which concentrates on the specific environmental settings of organisations, to examine the influence of management accounting departments within German municipal administrations. Our findings indicate that as the size of municipalities increases, the level of their administrative performance decreases. We additionally show that this negative effect can be mitigated when management accounting is seen as being highly relevant and when the management accounting department performs well. Furthermore, a comparison of the accounting systems (cash versus accrual accounting) used in municipal administrations reveals that a successful working management accounting department can only exert a positive effect when the municipal administration acts under an accrual accounting regime.
Tensions Arising from Imposing NPM in Australian Public Universities: A Management Perspective
Authors: Christopher Joe , Leung Philomena
Published: April 2015

This study seeks to identify the characteristics causing tensions in the move towards a corporate culture in Australian public universities. The findings reveal ongoing structural, competency and behavioral issues contributing to the tensions. Two theoretical propositions have emerged regarding the status of the change process. First, the change to a corporate culture is slow but continuing. Second, universities have accepted that public sector, collegial and corporate cultures have to co‐exist, thus adopting an adapted version of new public management (NPM). These findings provide avenues for further research to confirm both the characteristics and theoretical propositions.
The Removal of a Specialist Oversight Body for Local Public Audit: Insights from the Health Service in England
Authors: Ellwood Sheila , Garcia‐Lacalle Javier
Published: April 2015

The abolition of the Audit Commission in England and Wales removes the ‘protector of the public purse’. The oversight body and its audit practice are largely replaced by the private sector regime and audit firms. We analyse the audit market for health service foundation trusts, an area of local public audit that operates without oversight from the Commission. We find evidence of premiums paid to some Big4 firms and that the presence of specialist public service auditors results in fee discounts. The firms limit their liability and assurance of audit quality is reduced under new audit regimes and governance structures.
Subchronic administration of riparin III induces antidepressive‐like effects and increases BDNF levels in the mouse hippocampus
Authors: Vasconcelos Auriana S. , Oliveira Iris C.M. , Vidal Laura T.M. , Rodrigues Gabriel C. , Gutierrez Stanley J.C. , Barbosa‐Filho José M. , Vasconcelos Silvânia M.M. , de França Fonteles Marta M. , Gaspar Danielle M. , de Sousa Francisca C.F.
Published: April 2015

Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone‐induced chronic depression model. Swiss female mice, 22–25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween‐80, SC+ vehicle 2: distilled water emulsified with 2% Tween‐80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain‐derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one‐way anova, followed by Newman–Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders.
The effect of various morphine weaning regimens on the sequelae of opioid tolerance involving physical dependency, anxiety and hippocampus cell neurodegeneration in rats
Authors: Motaghinejad Majid , Karimian Seyed Morteza , Motaghinejad Ozra , Shabab Behnaz , Asadighaleni Majid , Fatima Sulail
Published: April 2015

Chronic consumption of morphine induces physical dependency, anxiety, and neurodegeneration. In this study, morphine on its own has been used for the management of morphine‐induced dependency, oxidative stress, and apoptosis. Forty‐eight male rats were randomly divided into six groups. Rats in groups 1–5 were made morphine dependent by an increasing manner of morphine for 7 days (15–45 mg/kg). For the next 14 days, morphine was administered using the following regimen: (i) once daily 45 mg/kg (positive controls), (ii) the same dose at additional intervals (6 h longer than the previous intervals each time), (iii) 45 mg/kg of morphine at irregular intervals like of 12, 24, 36 h, (iv) decreasing dose once daily (every time 2.5 mg/kg less than the former dosage). Group 5 received 45 mg/kg of morphine and 10 mg/kg of SOD mimetic agent (M40401) injection per day. Group 6 (negative control) received saline solution only. On day 22, all animals received naloxone (3 mg/kg) and their Total Withdrawal Index (TWI) and blood cortisol levels were measured. After drug treatment, hippocampus cells were isolated, and oxidative, antioxidative, and apoptotic factors were evaluated. Various regimens of morphine reduced TWI, cortisol levels, Bax activity, caspase‐3, caspase‐9, TNF‐α, and IL‐1β and lipid peroxidation. In all treatment groups, GSH level, superoxide dismutase, glutathione peroxidase, and Bcl‐2 activity were significantly increased. Furthermore, SOD mimetic agent c diminished morphine effect on SOD activity. Thus, varying the dosage regimen of morphine can reduce the severity of morphine‐induced dependency and neurodegeneration.
In situ adaptive response to climate and habitat quality variation: spatial and temporal variation in European badger (Meles meles) body weight
Authors: Byrne Andrew W. , Fogarty Ursula , O'Keeffe James , Newman Chris
Published: April 2015

Variation in climatic and habitat conditions can affect populations through a variety of mechanisms, and these relationships can act at different temporal and spatial scales. Using post‐mortem badger body weight records from 15 878 individuals captured across the Republic of Ireland (7224 setts across ca. 15 000 km2; 2009–2012), we employed a hierarchical multilevel mixed model to evaluate the effects of climate (rainfall and temperature) and habitat quality (landscape suitability), while controlling for local abundance (unique badgers caught/sett/year). Body weight was affected strongly by temperature across a number of temporal scales (preceding month or season), with badgers being heavier if preceding temperatures (particularly during winter/spring) were warmer than the long‐term seasonal mean. There was less support for rainfall across different temporal scales, although badgers did exhibit heavier weights when greater rainfall occurred one or 2 months prior to capture. Badgers were also heavier in areas with higher landscape habitat quality, modulated by the number of individuals captured per sett, consistent with density‐dependent effects reducing weights. Overall, the mean badger body weight of culled individuals rose during the study period (2009–2012), more so for males than for females. With predicted increases in temperature, and rainfall, augmented by ongoing agricultural land conversion in this region, we project heavier individual badger body weights in the future. Increased body weight has been associated with higher fecundity, recruitment and survival rates in badgers, due to improved food availability and energetic budgets. We thus predict that climate change could increase the badger population across the Republic of Ireland. Nevertheless, we emphasize that, locally, populations could still be vulnerable to extreme weather variability coupled with detrimental agricultural practice, including population management.
Plant community structure regulates responses of prairie soil respiration to decadal experimental warming
Authors: Xu Xia , Shi Zheng , Li Dejun , Zhou Xuhui , Sherry Rebecca A. , Luo Yiqi
Published: April 2015

Soil respiration is recognized to be influenced by temperature, moisture, and ecosystem production. However, little is known about how plant community structure regulates responses of soil respiration to climate change. Here, we used a 13‐year field warming experiment to explore the mechanisms underlying plant community regulation on feedbacks of soil respiration to climate change in a tallgrass prairie in Oklahoma, USA. Infrared heaters were used to elevate temperature about 2 °C since November 1999. Annual clipping was used to mimic hay harvest. Our results showed that experimental warming significantly increased soil respiration approximately from 10% in the first 7 years (2000–2006) to 30% in the next 6 years (2007–2012). The two‐stage warming stimulation of soil respiration was closely related to warming‐induced increases in ecosystem production over the years. Moreover, we found that across the 13 years, warming‐induced increases in soil respiration were positively affected by the proportion of aboveground net primary production (ANPP) contributed by C3 forbs. Functional composition of the plant community regulated warming‐induced increases in soil respiration through the quantity and quality of organic matter inputs to soil and the amount of photosynthetic carbon (C) allocated belowground. Clipping, the interaction of clipping with warming, and warming‐induced changes in soil temperature and moisture all had little effect on soil respiration over the years (all P > 0.05). Our results suggest that climate warming may drive an increase in soil respiration through altering composition of plant communities in grassland ecosystems.
Equivocal ALK fluorescence in‐situ hybridization (FISH) cases may benefit from ancillary ALKFISH probe testing
Authors: Selinger Christina , Cooper Wendy , Lum Trina , McNeil Catriona , Morey Adrienne , Waring Paul , Amanuel Benhur , Millward Michael , Peverall Joanne , Van Vliet Chris , Christie Michael , Tran Yen , Diakos Connie , Pavlakis Nick , Gill Anthony J , O'Toole Sandra
Published: April 2015

Aims

Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non‐small‐cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib. The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status.

Methods and results

ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break‐apart probe (Abbott Molecular). ALK immunohistochemistry was performed with 5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed discordance between the two FISH probes. All other cases were concordant. The TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK‐rearranged, and 60% of these had EML4 as the translocation partner. Within the group of 14 equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of these showed EML4 rearrangement. Of the six equivocal cases that received crizotinib, four showed clinical benefit.

Conclusions

The ALK/EML4 TriCheck FISH probe may be useful for the detection of ALK rearrangements, especially in borderline or atypical cases, where an additional unique ALK FISH probe may provide further confirmation of rearrangement.