bluuebunny/crossref_metadata_2025 huggingface dataset:
Impulsivity and Alcohol Dependence Treatment Completion: Is There a Neurocognitive Risk Factor at Treatment Entry?
Authors: Rupp Claudia I. , Beck J. Katharina , Heinz Andreas , Kemmler Georg , Manz Sarah , Tempel Katharina , Fleischhacker W. Wolfgang
Published: December 2015

Background

Although there is considerable support for the relationship between impulsivity and alcohol dependence, little is known about the impact of neurocognitive aspects of impulsivity on treatment outcome. The aim of this study was to prospectively investigate the impact of neurocognitive impulsivity at treatment onset on treatment completion.

Methods

Forty‐three alcohol‐dependent patients entering inpatient treatment for alcohol dependence completed neurocognitive measures of impulsivity at the beginning of treatment. Assessments included prototypical measures of impulsive action (Go/No‐go task [GNG] and Stop Signal Task [SST]) and impulsive choice (Delay Discounting Test [DDT], and Iowa Gambling Task). According to treatment outcomes, patients were divided into a patient group with regular treatment completion (e.g., with planned discharges, and without relapse during treatment) or irregular treatment course (e.g., premature and unplanned termination of treatment, “dropout,” and/or relapse).

Results

Results show that, relative to patients completing treatment in a regular fashion (regular treatment completers [RTC]; 67%), those with an irregular course of treatment (relapse and/or dropout) (irregular treatment completers [ITC]; 33%) had significantly poorer GNG response inhibition performance (p = 0.011), and showed a trend toward greater delay discounting (DDT; p = 0.052) at treatment onset. Additional logistic regression analyses identified poor GNG response inhibition performance as a significant predictor for an irregular treatment course (GNG: p = 0.021; DDT: p = 0.067), particularly for relapse (GNG: p = 0.023).

Conclusions

Neurocognitive impulsivity impacts upon treatment completion and appears sensitive for the prediction of relapse and dropout in alcohol‐dependent patients. Poorer GNG response inhibition and a tendency toward steeper discounting of delayed rewards should be regarded as neurocognitive risk factors, which can be identified early in the course of alcohol dependence treatment.
Inventory of Novel Animal Models Addressing Etiology of Preeclampsia in the Development of New Therapeutic/Intervention Opportunities
Authors: Erlandsson Lena , Nääv Åsa , Hennessy Annemarie , Vaiman Daniel , Gram Magnus , Åkerström Bo , Hansson Stefan R.
Published: December 2015

Preeclampsia is a pregnancy‐related disease afflicting 3–7% of pregnancies worldwide and leads to maternal and infant morbidity and mortality. The disease is of placental origin and is commonly described as a disease of two stages. A variety of preeclampsia animal models have been proposed, but all of them have limitations in fully recapitulating the human disease. Based on the research question at hand, different or multiple models might be suitable. Multiple animal models in combination within vitroorex vivostudies on human placenta together offer a synergistic platform to further our understanding of the etiology of preeclampsia and potential therapeutic interventions. The described animal models of preeclampsia divide into four categories (i) spontaneous, (ii) surgically induced, (iii) pharmacologically/substance induced, and (iv) transgenic. This review aims at providing an inventory of novel models addressing etiology of the disease and or therapeutic/intervention opportunities.
Face to face, person to person: Skills and attributes deployed by rural mental health clinicians when engaging with consumers
Authors: Procter Nicholas , Ferguson Monika , Backhouse Julia , Cother Ingrid , Jackson Adrian , Murison Julie , Reilly Julie‐Anne
Published: December 2015

Objective

The purpose of this study was to identify the skills and attributes deployed by rural mental health clinicians when engaging with consumers in the community mental health context.

Design

Reflecting the exploratory nature of this research, a semi‐structured focus group was conducted.

Setting

One community mental health service in regional South Australia (catchment area = approximately 60 000 people).

Participants

Nine mental health clinicians.

Interventions

Not applicable.

Main outcome measures

Participants’ focus group comments were explored qualitatively using thematic analysis.

Results

Three major themes were identified: (i) limitations to providing mental health care in the rural environment (increased consumer vulnerability, limited services, increased risk, and stigma); (ii) universal engagement approaches (being consumer‐focused, appropriate communication, facilitating a connection and normalising the experience); (iii) indicated and targeted strategies for engagement (flexible and creative delivery of care, a whole of community approach, being multiskilled and technology use).

Conclusions

Although engaging with consumers involves many skills and attributes employed universally across mental health settings, the rural clinician's ability to navigate the environment and utilise this to provide consumer care is equally important to the engagement process. Specifically, these findings highlight the preference of rural mental health clinicians towards a person‐centred approach, networking with others in the community when providing care. Understanding how best to maximise the nature of a rural environment, such as facilitating relationships between clinicians and others in the community, will contribute to optimised care.
Work and personal well‐being of nurses in Queensland: Does rurality make a difference?
Authors: Hegney Desley , Eley Robert , Osseiran‐Moisson Rebecca , Francis Karen
Published: December 2015

Objective

This study aims to ascertain if differences exist in the perception of the professional practice environment and personal well‐being of nurses across different geographical areas in Queensland.

Design

This paper was performed on a prospective, self‐report cross‐sectional on‐line survey.

Setting

The study was conducted among the nurses employed in public and private health care settings: acute hospitals, community health and aged care in Queensland, Australia.

Participants

Participants of this study were 1608 registered and enrolled nurses and assistants in nursing, current members of the Queensland Nurses Union in 2013 and who provided a workplace postcode. One thousand eight of these participants worked in major cities, while 382 in rural locations and 238 in remote areas.

Interventions

None.

Main outcome measures

Scores of well‐being as determined by the following scales: the Depression, Anxiety and Stress Scale, the Professional Quality of Life Scale version 5, the Connor–Davidson Resilience Scale and of the Professional Practice Environment using the Practice Environment Scale – Nursing Work Index Revised.

Results

Nurses employed in major cities perceived ‘nursing foundations for quality care’ more favourably than those from other settings. Remote area nurses had lower levels of secondary traumatic stress than nurses in major cities and rural areas. There was no difference between nurses across their geographical locations for stress, anxiety, depression, compassion satisfaction, burnout, resilience and the four other measures of the Practice Environment Scale.

Conclusions

The study findings provide new data suggesting that, with the exception of secondary traumatic stress, the personal well‐being of nurses does not differ across geographical settings. Similarly, with the exception of the subscale of ‘nursing foundations for quality care’ there was no difference in perceptions of the professional practice environment. As secondary traumatic stress is associated with burnout, this finding needs to be investigated further.
Birthing in rural South Australia: The changing landscape over 20 years
Authors: Sweet Linda P. , Boon Virginia A. , Brinkworth Vanessa , Sutton Sarah , Werner Allison F.
Published: December 2015

Objective

To map trends in the maternity service availability for rural women in South Australia and identify the frequency of women birthing outside of their region of residence.

Design

A retrospective review of birth location for rural South Australian women from 1991 to 2010.

Setting

Rural maternity units in South Australia.

Participants

Birthing statistics from the Pregnancy Outcomes Statistics Unit in South Australia

Main outcome measures

Rural birth statistics, including place of birth in relation to place of residence and location of maternity units.

Results

Over 60% of maternity units across rural South Australia have closed since 1991. There has been a rise in the percentage of women birthing away from their usual region of residence, rising from 18% in 1991–1995 to 24% in 2006–2010.

Conclusions

This study has revealed that almost one quarter of all women residing in rural South Australia relocate to another area to give birth. This is a significant concern for rural women and their families through the expectation of separation, and for the local health services who might now not have the facilities and skills to manage an unplanned maternity presentation. These concerns need to be considered and addressed in order to provide safe and effective care for child‐bearing women regardless of location.
Chronic kidney disease in an Aboriginal population: A nurse practitioner‐led approach to management
Authors: Barrett Elizabeth , Salem Lesley , Wilson Sue , O'Neill Claire , Davis Kathleen , Bagnulo Sharif
Published: December 2015

Problem

Chronic kidney disease (CKD) is a significant health problem impacting Australia's Aboriginal and Torres Strait Islander population. After age adjustment, the prevalence of kidney disease is 3.7 times higher in Aboriginal people and 7.3 times higher for end‐stage kidney disease compared with the wider population. Yet at an Aboriginal Community Controlled Health Service (ACCHS) with a significant patient population, fewer than expected numbers of Aboriginal patients were identified with CKD.

Design

The ACCHS engaged a nurse practitioner to lead a systematic approach to the identification and treatment of CKD. Setting: This nurse practitioner‐led approach to CKD was developed and implemented at a rural NSW ACCHS, with the support of a partnership formed between the nurse practitioner, the ACCHS, a nephrologist from a referral hospital and a statewide NGO.

Key measures for improvement

The primary measure for improvement has been to identify and stage patients with CKD and establish management plans as appropriate.

Strategies for change

This nurse‐led project was established to: (i) identify patients with CKD; (ii) provide access for CKD patients to appropriate services; (iii) commence pharmacological and non‐pharmacological strategies that enable remission or regression of CKD; and (iv) educate practice GPs and other staff members on CKD clinical guidelines and best practice.

Effects of change

The CKD project has improved access to essential health care for vulnerable and at‐risk populations, with 187 patients to date having been identified with kidney disease and staged for its severity.

Lessons learnt

The need for strong multi‐disciplinary teamwork has been demonstrated with good communication strategies implemented.
Tele‐Derm National: A decade of teledermatology in rural and remote Australia
Authors: Byrom Lisa , Lucas Lex , Sheedy Vicki , Madison Kim , McIver Lachlan , Castrisos George , Alfonzo Christina , Chiu Frank , Muir Jim
Published: December 2015

Objective

To identify the current scope of Tele‐Derm, the types of dermatological complaints experienced in the rural primary care setting, and to assess the quality of patient clinical information provided to the consultant dermatologist.

Design

Retrospective case analysis.

Setting

Tele‐Derm National is an initiative of the Australian College of Rural and Remote Medicine and has been providing online educational and consultational services in dermatology to doctors Australia‐wide for over a decade.

Participants

Patient cases that were submitted to Tele‐Derm for specialist dermatologist advice.

Interventions

Audit of submitted cases.

Main outcome measures

The types of patient presentations and reason for submission for specialist opinion were analysed. The quality of clinical information provided was also evaluated.

Results

A total of 406 cases submitted over 2012–2013 were analysed. Most patients were from the outpatient setting with ‘rash’ or dermatitis (66%). Almost one‐third of patients were paediatric cases. The average time from submission to dermatologist reply was 5.5 hours. Clinical photos were provided in 83% of cases and 73% of these were assessed as being of good quality. Management advice was provided in 77% of cases, of which reference to the case‐based learning modules on Tele‐Derm was made in 21% of cases. Patient outcome was largely unknown (83%).

Conclusion

This study identified some of the common dermatological complaints presenting to rural and remote primary care doctors in Australia. The unique addition of professional development in Tele‐Derm can be used as an adjunct to advice provided to the rural doctors seeking advice for patient management.
Losing the rural nursing workforce: Lessons learnt from resigning nurses
Authors: Bragg Susan , Bonner Ann
Published: December 2015

Background

Australian workforce planning predicts a shortfall of nurses by 2025 with rural areas being most at risk. Rural areas have lower retention rates of nurses than metropolitan areas, with remote communities experiencing an even higher turnover of nursing staff. There have been few studies that examine the impact of nurse resignations on rural nursing workforces.

Objective

This paper is abstracted from a larger study into the reasons why nurses resign from rural hospitals and explores the resignation period.

Design

A qualitative study using grounded theory methods. Following in‐depth interviewing and transcription, data analysis occurred with the assistance of NVivo software.

Setting

Rural NSW.

Participants

Twelve registered nurses who had resigned from rural NSW hospitals and not for reasons of retirement, maternity leave or relocation; two participants were re‐interviewed.

Results

While the overall study identified a grounded theory which explained rural nurses resign from hospitals due to a conflict of values, three additional themes emerged about the resignation practices at rural hospitals. The first theme identified a ‘window period’ which was an opportunity for the nurse to be retained. The second theme identified that nurses who had resigned were not involved in formal exit processes such as exit interviews. The third theme captured the flow‐on effect from rural nurse resignations resulting in nurses leaving the profession of nursing.

Conclusion

To facilitate nurse retention, it is important that rural hospitals manage nurse resignations more effectively. This includes re‐examining resignation procedures, how nurses are treated and collecting meaningful data to inform retention strategies.
The first year experience of occupational therapy students at an Australian regional university: Promoting student retention and developing a regional and remote workforce
Authors: Boehm Jackie , Cordier Reinie , Thomas Yvonne , Tanner Bronwyn , Salata Karen
Published: December 2015

Objective

Student retention at regional universities is important in addressing regional and remote workforce shortages. Students attending regional universities are more likely to work in regional areas. First year experience at university plays a key role in student retention. This study aimed to explore factors influencing the first year experience of occupational therapy students at a regional Australian university.

Design

Surveys were administered to 58 second year occupational therapy students in the first week of second year. Data were analysed using descriptive statistics, inferential statistics (Pearson χ2; Spearman rho) and summarising descriptive responses.

Setting

An Australian regional university.

Participants

Second year undergraduate occupational therapy students.

Main outcome measures

Factors influencing students' decisions to study and continue studying occupational therapy; factors enhancing first year experience of university.

Results

Fifty‐four students completed the survey (93.1%). A quarter (25.9%) of students considered leaving the course during the first year. The primary influence for continuing was the teaching and learning experience. Most valued supports were orientation week (36.7%) and the first year coordinator (36.7%).

Conclusion

The importance of the first year experience in retaining occupational therapy students is highlighted. Engagement with other students and staff and academic support are important factors in facilitating student retention. It is important to understand the unique factors influencing students' decisions, particularly those from regional and remote areas, to enter and continue in tertiary education to assist in implementing supports and strategies to improve student retention.
Median Sternotomy or Right Thoracotomy Techniques for Total Artificial Heart Implantation in Calves
Authors: Karimov Jamshid H. , Moazami Nader , Sunagawa Gengo , Kobayashi Mariko , Byram Nicole , Sale Shiva , Such Kimberly A. , Horvath David J. , Golding Leonard A.R. , Fukamachi Kiyotaka
Published: December 2015

The choice of optimal operative access technique for mechanical circulatory support device implantation ensures successful postoperative outcomes. In this study, we retrospectively evaluated the median sternotomy and lateral thoracotomy incisions for placement of the Cleveland Clinic continuous‐flow total artificial heart (CFTAH) in a bovine model. The CFTAH was implanted in 17 calves (Jersey calves; weight range, 77.0–93.9 kg) through a median sternotomy (n = 9) or right thoracotomy (n = 8) for elective chronic implantation periods of 14, 30, or 90 days. Similar preoperative preparation, surgical techniques, and postoperative care were employed. Implantation of the CFTAH was successfully performed in all cases. Both methods provided excellent surgical field visualization. After device connection, however, the median sternotomy approach provided better visualization of the anastomoses and surgical lines for hemostasis confirmation and repair due to easier device displacement, which is severely limited following right thoracotomy. All four animals sacrificed after completion of the planned durations (up to 90 days) were operated through full median sternotomy. Our data demonstrate that both approaches provide excellent initial field visualization. Full median sternotomy provides larger viewing angles at the anastomotic suture line after device connection to inflow and outflow ports.
Partnering with parents to disclose Klinefelter syndrome to their child
Authors: Tremblay Isabelle , Van Vliet Guy , Gonthier Monique , Janvier Annie
Published: December 2015

In paediatrics, a diagnosis of Klinefelter syndrome can occur after prenatal testing or because of symptoms such as learning difficulties or incomplete puberty. After the diagnosis, parents have to decide when and how to speak about this condition to their child. Parents and healthcare professionals (HCPs) may have different perceptions related to disclosure of this diagnosis. Due to the absence of clear guidelines, parents and HCPs may feel uncomfortable discussing the condition and may hide the truth in a prolonged fashion.

Conclusion

For patients with a prenatal diagnosis, we recommend a gradual and personalised disclosure process starting between the ages of 5 and 13 years. For older patients, a personalised approach should also be the goal. Various communication strategies and recommendations regarding disclosure of Klinefelter syndrome are proposed.
Early life events and motor development in childhood and adolescence: a longitudinal study
Authors: Grace Tegan , Bulsara Max , Robinson Monique , Hands Beth
Published: December 2015

Aim

Few studies have reported on early life risk factors for motor development outcomes past childhood. Antenatal, perinatal and neonatal factors affecting motor development from late childhood to adolescence were explored. As sex differences in motor development have been previously reported, males and females were examined separately.

Methods

Participants (n = 2868) were from the Western Australian Pregnancy Cohort Study. Obstetric and neonatal data were examined to determine factors related to motor development at 10 (n = 1622), 14 (n = 1584) and 17 (n = 1221) years. The Neuromuscular Development Index (NDI) of the McCarron Assessment of Motor Development determined offspring motor proficiency. Linear mixed models were developed to allow for changes in motor development over time.

Results

Maternal pre‐eclampsia, Caesarean section and low income were negatively related to male and female motor outcomes. Lower percentage of optimal birthweight was related to a lower male NDI. Younger maternal age, smoking during early pregnancy and stress during later pregnancy were related to lower female NDIs.

Conclusion

Events experienced during pregnancy were related to motor development into late adolescence. Males and females were influenced differently by antenatal and perinatal risk factors; this may be due to sex‐specific developmental pathways.
Somatic assessments of 120 Swedish children taken into care reveal large unmet health and dental care needs
Authors: Kling Stefan , Vinnerljung Bo , Hjern Anders
Published: December 2015

Aim

For decades, non‐Nordic countries have consistently reported high rates of somatic health problems among children placed in care by the authorities. This study examined the unmet health and dental care needs of Swedish children in foster and residential care.

Methods

The health of 120 consecutive children aged 0–17 years, who had recently been placed in foster or residential care in one Swedish region, was assessed by an experienced paediatrician using patient records, their medical history and a physical examination.

Results

Following the assessments, 51% of the subjects received at least one referral to a specialist or to primary care, either for a previously undetected medical condition or for a follow‐up of a previously detected condition noted in their patient records. The study showed that 40% of the girls and 33% of boys were overweight and completed vaccination rates were only 86% for children up to the age of six and 68% for 7‐ to 17‐year‐olds. Half of the 7‐ to 17‐year‐olds had untreated dental decay.

Conclusion

Our study revealed a large unmet need for health and dental care interventions among children placed in foster care and residential care and a systematic strategy is required to address those needs.
COLLECTIVE ACTION AND ASPIRATIONS: THE IMPACT OF COOPERATIVES ON ETHIOPIAN COFFEE FARMERS’ ASPIRATIONS
Authors: MOJO Dagne , FISCHER Christian , DEGEFA Terefe
Published: December 2015

Aspirations motivate behaviours, serve to mobilize and direct energy into actions, and are regarded as important determinants of success. Given the importance of aspirations and their formation in social interaction, the objective of this article is to evaluate if cooperative membership can have effects on members' aspiration levels. Face‐to‐face interviews were conducted with 305 Ethiopian coffee farmers on their aspired levels in five dimensions of their lives. Results, using a propensity score matching technique, show that membership in cooperatives significantly improves the aspiration levels of the members. The article emphasizes the utilization of this hidden but important benefit of cooperatives.
ANALYSIS OF THE POSSIBILITIES FOR EXPANSION OF SERVICES IN TANZANIAN SAVINGS AND CREDITS CO‐OPERATIVE SOCIETIES: LEARNING FROM ECONOMIES OF SCALE
Authors: NDIEGE Benson Otieno , QIN Xuezhi , MASSAMBU Daud , TOWO Esther N.
Published: December 2015

Savings and Credit Co‐operative Societies (SACCOS) increasingly recognized as the valuable tool for economic development in low‐income countries. However, recently researchers reported that one of their primary challenges to their expansion is the high level of inefficient. In this study, we analyzed the relationship between growth and efficiency of SACCOS using economies of scale concept. Then we address the role of management of the capital structure and allocation of resources in the expansion of SACCOS. The study used financial statement data from 60 SACCOS in Tanzania for the period of 2004–2011. The findings supports that most of SACCOS are small and cost inefficient because the industry is young, but, the efficiency increases as SACCOS expand. Second the allocation of resources in liquid, financial and non‐financial investment leads to no expansion in SACCOS. Thus, the growth of SACCOS via increasing loan to members, members’ savings, shares, and institutional capital should be encouraged as it increases the efficiency of SACCOS. Also, SACCOS should minimize the allocation of assets in other investments which are different from credit to members.
Cluster Adjusted Regression for Displaced Subject Data (CARDS): Marginal Inference Under Potentially Informative Temporal Cluster Size Profiles
Authors: Bible Joe , Beck James D. , Datta Somnath
Published: December 2015

Ignorance of the mechanisms responsible for the availability of information presents an unusual problem for analysts. It is often the case that the availability of information is dependent on the outcome. In the analysis of cluster data we say that a condition for informative cluster size (ICS) exists when the inference drawn from analysis of hypothetical balanced data varies from that of inference drawn on observed data. Much work has been done in order to address the analysis of clustered data with informative cluster size; examples include Inverse Probability Weighting (IPW), Cluster Weighted Generalized Estimating Equations (CWGEE), and Doubly Weighted Generalized Estimating Equations (DWGEE). When cluster size changes with time, i.e., the data set possess temporally varying cluster sizes (TVCS), these methods may produce biased inference for the underlying marginal distribution of interest. We propose a new marginalization that may be appropriate for addressing clustered longitudinal data with TVCS. The principal motivation for our present work is to analyze the periodontal data collected by Beck et al. (1997, Journal of Periodontal Research 6, 497–505). Longitudinal periodontal data often exhibits both ICS and TVCS as the number of teeth possessed by participants at the onset of study is not constant and teeth as well as individuals may be displaced throughout the study.
Interpretable Functional Principal Component Analysis
Authors: Lin Zhenhua , Wang Liangliang , Cao Jiguo
Published: December 2015

Functional principal component analysis (FPCA) is a popular approach to explore major sources of variation in a sample of random curves. These major sources of variation are represented by functional principal components (FPCs). The intervals where the values of FPCs are significant are interpreted as where sample curves have major variations. However, these intervals are often hard for naïve users to identify, because of the vague definition of “significant values”. In this article, we develop a novel penalty-based method to derive FPCs that are only nonzero precisely in the intervals where the values of FPCs are significant, whence the derived FPCs possess better interpretability than the FPCs derived from existing methods. To compute the proposed FPCs, we devise an efficient algorithm based on projection deflation techniques. We show that the proposed interpretable FPCs are strongly consistent and asymptotically normal under mild conditions. Simulation studies confirm that with a competitive performance in explaining variations of sample curves, the proposed FPCs are more interpretable than the traditional counterparts. This advantage is demonstrated by analyzing two real datasets, namely, electroencephalography data and Canadian weather data.
Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003
Authors: Hough Rachael , Rowntree Clare , Goulden Nick , Mitchell Chris , Moorman Anthony , Wade Rachel , Vora Ajay
Published: December 2015

Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi‐centre, prospective, randomized phase III trial, investigating treatment intensification or de‐escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7·3%) were aged 16–24 years. These patients were significantly more likely to have high risk MRD compared to 10–15 year olds (47·9% vs. 36·6%, P = 0·004). Nonetheless, 5‐year event‐free survival for the TYA cohort (aged 16–24 years) was 72·3% [95% confidence interval (CI): 66·2–78·4] overall and 92·6% (95% CI: 85·5–99·7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged ≥10 years compared to those aged 9 or younger (P < 0·0001) and novel age‐specific patterns of treatment‐related toxicity were observed. TYA patients obtain excellent outcomes with a risk‐ and response‐adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities.
The evolution of T‐cell depletion in haploidentical stem‐cell transplantation
Authors: Or‐Geva Noga , Reisner Yair
Published: December 2015

T‐cell depletion (TCD) can prevent the onset of graft‐versus‐host disease (GvHD) in animal models of bone marrow transplantation; this manipulation enabled the successful application in the 1980s of T‐cell depleted bone marrow (BM) for the treatment of babies with severe combined immune deficiency (SCID). However, in leukaemia patients, implementation of T‐cell depletion has been more difficult, especially due to high rate of graft‐rejection, leukaemia relapse and delayed immune reconstitution. These hurdles were gradually overcome by modifying the cell composition of the graft, and by reducing the toxicities associated with conditioning protocols. Although no ‘gold standard’ TCD method exists, T‐cell depletion in its modern forms could offer clinical benefit, even for patients with a matched sibling donor.
High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3‐ITD,KMT2A‐PTD, and NUP98‐NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 trial
Authors: Shiba Norio , Ohki Kentaro , Kobayashi Tohru , Hara Yusuke , Yamato Genki , Tanoshima Reo , Ichikawa Hitoshi , Tomizawa Daisuke , Park Myoung‐ja , Shimada Akira , Sotomatsu Manabu , Arakawa Hirokazu , Horibe Keizo , Adachi Souichi , Taga Takashi , Tawa Akio , Hayashi Yasuhide
Published: December 2015

Recent reports described the NUP98‐NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98‐NSD1 fusion. PRDM16 gene expression levels were measured via real‐time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P < 0·001; inv(16), 0% vs. 100%, P < 0·001; KMT2A (also termed MLL)‐ partial tandem duplication, 100% vs. 0%, P < 0·001; NUP98‐NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event‐free survival (EFS) among PRDM16‐overexpressing patients were significantly worse than in patients with low PRDM16 expression (3‐year OS: 51% vs. 81%, P < 0·001, 3‐year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3‐internal tandem duplication‐positive AML patients (3‐year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate‐risk cytogenetic profiles and was independently associated with an adverse outcome.
Clinical features and prognostic factors in solitary plasmacytoma
Authors: Finsinger Paola , Grammatico Sara , Chisini Marta , Piciocchi Alfonso , Foà Robin , Petrucci Maria T.
Published: December 2015

This study aimed to review the clinical features and outcome of 53 patients with solitary plasmacytoma managed at our Institution between 1976 and 2012. Thirty‐five patients had bone solitary plasmacytoma and 18 extramedullary solitary plasmacytoma. Tumour sizes were larger in patients with bone involvement (P = 0·003). Treatment consisted of local radiotherapy (n = 26), radiotherapy + chemotherapy (n = 15), surgery (n = 4) and chemotherapy (n = 8); the local control rate was 94·3%. Progression to multiple myeloma was recorded in 20/35 (57·1%) patients with bone involvement and in 1/18 (5·5%) patients with extramedullary disease (P = 0·0003). The 5‐year overall survival (OS) rate was 78·4%; bone solitary plasmacytoma patients had a significantly worseOS(71·9% vs. 88·2%, respectively;P = 0·029) and 5‐year progression‐free survival (PFS; 53·0% vs. 88·5%;P = 0·0003) compared to extramedullary solitary plasmacytoma patients. On univariate analysis, bone disease and size (≥5 cm) impacted negatively onPFS(P = 0·0027 andP = 0·04, respectively). Bone disease also affectedOS(P = 0·04). In multivariate analysis bone location was the only independent prognostic factor forPFS(P = 0·0041) andOS(P = 0·021). Patients with bone solitary plasmacytoma have a significantly worse prognosis than extramedullary solitary plasmacytoma cases.
Retracted: Synthesis, Characterization, and Preclinical Evaluation of 99mTc‐Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer
Authors: Yadav Neelam , Chuttani Krishna , Mishra Anil K. , Singh Bachcha
Published: December 2015

The novel tetraaza macrobicyclic chelator 3,6,9,15‐tetraazabicyclo[9.3.1]pentadeca‐1(15),11,13‐triene‐2,10‐dione (TBPD) and pentaaza macrotricyclic chelator 9‐oxa‐3,6,12,15,21‐pentaazatricyclo[15,3,2,1]trieicos‐1(21),17,19‐triene‐2,7,11,16‐tetradione (OPTT) were synthesized, characterized, and radiolabeled with 99mTc to produce 99mTc‐TBPD and 99mTc‐OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of 99mTc‐TBPD and 99mTc‐OPTT was found 98% and 97%. In vitro serum stability of 99mTc‐TBPD was found to be 95.2%, while that of 99mTc‐OPTT 94.2% up to 24 h. Blood kinetics experiments of 99mTc‐labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of 99mTc‐TBPD and 99.42 ± 0.88% activity of 9mTc‐OPTT were cleared off blood stream at 24 h postadministration. The biological half‐life of 99mTc‐TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half‐life of 99mTc‐OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of 99mTc‐TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of 99mTc‐OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U‐87, U373 cell lines.
Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents
Authors: Rao Zhigang , Hu Hao , Tang Jiazhi , Liu Zhiying , Yang Yue , Qiu Guofu , Xiao Yuling , Liu Peng , Hu Xianming , Zhou Xiaoju , Hong Xuechuan
Published: December 2015

Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve–hemidiaphragms for their bioactivities. The initial separation of mono‐ and bis‐quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 μm) and 4g (0.37 μm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 μm). In addition, other bis‐quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure–activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series.
Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti‐Inflammatory Agents
Authors: Moneer Ashraf A. , Mohammed Khaled O. , El‐Nassan Hala B.
Published: December 2015

Two series of new 1‐(alkyl/aryl)‐3‐{2‐[(5‐oxo‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)amino]phenyl}thioureas 2a–h and 5‐[2‐(substituted amino)‐1H‐benzimidazol‐1‐yl]‐4H‐pyrazol‐3‐ols 3a–i were designed and synthesized as anti‐inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non‐selective inhibition of COX‐1 and COX‐2 enzymes which was consistent with their docking results. Compounds 2c, 2f, 2g, 3b, and 3g that showed the highest COX‐2 inhibitory activity were selected for further in vivo testing as anti‐inflammatory agents using diclofenac as a reference drug. Two of the test compounds (2c and 3b) showed potent anti‐inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti‐inflammatory agents was also provided.
Rapid Identification of Novel Inhibitors of the Human Aquaporin‐1 Water Channel
Authors: Patil Rajkumar V. , Xu Shouxi , van Hoek Alfred N. , Rusinko Andrew , Feng Zixia , May Jesse , Hellberg Mark , Sharif Najam A. , Wax Martin B. , Irigoyen Macarena , Carr Grant , Brittain Tom , Brown Peter , Colbert Damon , Kumari Sindhu , Varadaraj Kulandaiappan , Mitra Alok K.
Published: December 2015

Aquaporins (AQPs) are a family of membrane proteins that function as channels facilitating water transport in response to osmotic gradients. These play critical roles in several normal physiological and pathological states and are targets for drug discovery. Selective inhibition of the AQP1 water channel may provide a new approach for the treatment of several disorders including ocular hypertension/glaucoma, congestive heart failure, brain swelling associated with a stroke, corneal and macular edema, pulmonary edema, and otic disorders such as hearing loss and vertigo. We developed a high‐throughput assay to screen a library of compounds as potential AQP1 modulators by monitoring the fluorescence dequenching of entrapped calcein in a confluent layer of AQP1‐overexpressing CHO cells that were exposed to a hypotonic shock. Promising candidates were tested in a Xenopus oocyte‐swelling assay, which confirmed the identification of two lead classes of compounds belonging to aromatic sulfonamides and dihydrobenzofurans with IC50s in the low micromolar range. These selected compounds directly inhibited water transport in AQP1‐enriched stripped erythrocyte ghosts and in proteoliposomes reconstituted with purified AQP1. Validation of these lead compounds, by the three independent assays, establishes a set of attractive AQP1 blockers for developing novel, small‐molecule functional modulators of human AQP1.
Instrumental and Conventional Interpretations of Behavior Are Associated With Distinct Outcomes in Early Childhood
Authors: Clegg Jennifer M. , Legare Cristine H.
Published: December 2015

Four tasks (N = 191, 3‐ to 6‐year‐olds) examined the effect of instrumental versus conventional language cues on children's imitative fidelity of a necklace‐making activity, their memory and transmission of the activity, and their perceptions of functional fixedness. Children in the conventional condition imitated with higher fidelity, transmitted more of the modeled behavior, and showed higher levels of functional fixedness than children in the instrumental condition. There were no differences in children's memory of the activity between conditions demonstrating that memory alone does not explain differences in imitative fidelity. The data demonstrate that children's interpretation of behavior as instrumental or conventional has wide‐ranging implications for what children imitate, what they transmit to others, and how they reason about objects' functions.
Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone‐dependent severe asthma
Authors: Sehmi R. , Smith S. G. , Kjarsgaard M. , Radford K. , Boulet L.‐P. , Lemiere C. , Prazma C. M. , Ortega H. , Martin J. G. , Nair P.
Published: December 2015

Background

In severe asthmatics with persistent airway eosinophilia, blockade of interleukin‐5 has significant steroid‐sparing effects and attenuates blood and sputum eosinophilia. The contribution of local maturational processes of progenitors within the airways relative to the recruitment of mature cells from the peripheral circulation to the development of airway eosinophilia is not known. We hypothesize that local eosinophilopoiesis may be the predominant process that drives persistent airway eosinophilia and corticosteroid requirement in severe asthmatics.

Objectives

In a cross‐sectional study, the number and growth potential of eosinophil‐lineage‐committed progenitors (EoP) were assayed in 21 severe eosinophilic asthmatics, 19 mild asthmatics, eight COPD patients and eight normal subjects. The effect of anti‐IL‐5 treatment on mature eosinophils and EoP numbers was made in severe eosinophilic asthmatics who participated in a randomized clinical trial of mepolizumab (substudy of a larger GSK sponsored global phase III trial, MEA115575) where subjects received mepolizumab (100 mg, n = 9) or placebo (n = 8), as six monthly subcutaneous injections.

Results

Mature eosinophil and EoP numbers were significantly greater in the sputum of severe asthmatics compared with all other subject groups. In colony‐forming assays, EoP from blood of severe asthmatics demonstrated a greater response to IL‐5 than mild asthmatics. Treatment of severe asthmatics with mepolizumab significantly attenuated blood eosinophils and increased EoP numbers consistent with blockade of systemic eosinophilopoiesis. There was however no significant treatment effect on mature eosinophils, sputum EoP numbers or the prednisone maintenance dose.

Conclusions and Clinical Relevance

Patients with severe eosinophilic asthma have an exaggerated eosinophilopoeitic process in their airways. Treatment with 100 mg subcutaneous mepolizumab significantly attenuated systemic differentiation of eosinophils, but did not suppress local airway eosinophil differentiation to mature cells. Targeting IL‐5‐driven eosinophil differentiation locally within the lung maybe of relevance for optimal control of airway eosinophilia and asthma.
On the use of median‐joining networks in evolutionary biology
Authors: Kong Sungsik , Sánchez‐Pacheco Santiago J. , Murphy Robert W.
Published: December 2015

Median‐joining (MJ) was proposed as a method for phylogeographical analysis and is enjoying increasing popularity. Herein, we evaluate the efficacy of the approach as originally intended. We show that median‐joining networks (MJNs) are theoretically untenable for evolutionary inference, and that confusion has afflicted their use for over 15 years. The approach has two obvious shortcomings: its reliance on distance‐based phenetics (overall similarity instead of character transformations) and the lack of rooting (no direction or history). Given that evolution involves both change and time, and the absence of rooting removes time (ancestor–descendant relationships) from the equation, the approach cannot yield defensible evolutionary interpretations. We also examine the impact of MJ analyses on evolutionary biology via an analysis of citations and conclude that the spread of MJNs through the literature is difficult to explain, especially given the availability of character‐based analyses.
Is biological mesh interposition a valid option for complex or recurrent rectovaginal fistula?
Authors: Mege D. , Frasson M. , Maggiori L. , Panis Y.
Published: December 2015

Aim

Many surgical techniques are available for the treatment of rectovaginal fistula (RVF). There is hitherto little information on its treatment by biological mesh interposition. The aim of the present study was to analyse our results of RVF treatment using biological mesh interposition.

Method

Patients with RVF undergoing biological mesh interposition were identified. Success was defined by the absence of a diverting stoma and/or any vaginal discharge of faeces, flatus or mucous discharge.

Results

Ten women [median age 39 (24.5–65) years] were included. Nine (90%) had recurrent RVF, and the median number of previous attempts at closure was 2.5 (0−8). The main cause of RVF was Crohn's disease (40%). All patients had faecal diversion. No intra‐operative complications occurred from mesh interposition. Seven (70%) patients developed postoperative morbidity which was major (Dindo III) in two (20%). The primary success rate was 20% (2/10) but final success rate was achieved in 70% after reoperation with other procedures at 11.1 (2.7−13.1) months of follow‐up.

Conclusion

The study has shown disappointing results with biological mesh interposition for RVF with a healing rate lower than achieved by gracilis muscle interposition.
A prospective randomized trial on the use of Coca‐Cola Zero®vs water for polyethylene glycol bowel preparation before colonoscopy
Authors: Seow‐En I. , Seow‐Choen F.
Published: December 2015

Aim

The study aimed to determine whether Coca‐Cola (Coke) Zero is a safe and effective solvent for polyethylene glycol (PEG).

Method

Between December 2013 and April 2014, 209 healthy adults (115 men, 95 women) scheduled for elective colonoscopy were randomized to use either Coke Zero (n = 100) or drinking water (n = 109) with PEG as bowel preparation. Each patient received two sachets of PEG to dissolve in 2 l of solvent, to be completed 6 h before colonoscopy. Serum electrolytes were measured before and after preparation. Bowel cleanliness and colonoscopy findings were recorded. Palatability of solution, adverse effects, time taken to complete and willingness to repeat the preparation were documented via questionnaire.

Results

Mean palatability scores in the Coke Zero group were significantly better compared with the control group (2.31 ± 0.61 vs 2.51 ± 0.63, P = 0.019), with a higher proportion willing to use the same preparation again (55% vs 43%). The mean time taken to complete the PEG + Coke Zero solution was significantly faster (74 ± 29 min vs 86 ± 31 min, P = 0.0035). The quality of bowel cleansing was also significantly better in the Coke Zero group (P = 0.0297). There was no difference in the frequency of adverse events (P = 0.759) or the polyp detection rate (32% vs 31.2%). Consumption of either preparation did not significantly affect electrolyte levels or hydration status.

Conclusion

Coke Zero is a useful alternative solvent for PEG. It is well tolerated, more palatable, leads to quicker consumption of the bowel preparation and results in better quality cleansing.