bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and seasonality of respiratory viral infections in hospitalized children in Kuala Lumpur, Malaysia: a retrospective study of 27 years
Authors: Khor Chee-Sieng , Sam I-Ching , Hooi Poh-Sim , Quek Kia-Fatt , Chan Yoke-Fun
Published: March 2012

Background

Viral respiratory tract infections (RTI) are relatively understudied in Southeast Asian tropical countries. In temperate countries, seasonal activity of respiratory viruses has been reported, particularly in association with temperature, while inconsistent correlation of respiratory viral activity with humidity and rain is found in tropical countries. A retrospective study was performed from 1982-2008 to investigate the viral etiology of children (≤ 5 years old) admitted with RTI in a tertiary hospital in Kuala Lumpur, Malaysia.

Methods

A total of 10269 respiratory samples from all children ≤ 5 years old received at the hospital's diagnostic virology laboratory between 1982-2008 were included in the study. Immunofluorescence staining (for respiratory syncytial virus (RSV), influenza A and B, parainfluenza types 1-3, and adenovirus) and virus isolation were performed. The yearly hospitalization rates and annual patterns of laboratory-confirmed viral RTIs were determined. Univariate ANOVA was used to analyse the demographic parameters of cases. Multiple regression and Spearman's rank correlation were used to analyse the correlation between RSV cases and meteorological parameters.

Results

A total of 2708 cases were laboratory-confirmed using immunofluorescence assays and viral cultures, with the most commonly detected being RSV (1913, 70.6%), parainfluenza viruses (357, 13.2%), influenza viruses (297, 11.0%), and adenovirus (141, 5.2%). Children infected with RSV were significantly younger, and children infected with influenza viruses were significantly older. The four main viruses caused disease throughout the year, with a seasonal peak observed for RSV in September-December. Monthly RSV cases were directly correlated with rain days, and inversely correlated with relative humidity and temperature.

Conclusion

Viral RTIs, particularly due to RSV, are commonly detected in respiratory samples from hospitalized children in Kuala Lumpur, Malaysia. As in temperate countries, RSV infection in tropical Malaysia also caused seasonal yearly epidemics, and this has implications for prophylaxis and vaccination programmes.
Gender differences in alcohol-related non-consensual sex; cross-sectional analysis of a student population
Authors: Gunby Clare , Carline Anna , Bellis Mark A , Beynon Caryl
Published: March 2012

Background

Sexual offences are a global public health concern. Recent changes in the law in England and Wales have dramatically altered the legal landscape of sexual offences, but sexual assaults where the victim is voluntarily intoxicated by alcohol continue to have low conviction rates. Worldwide, students are high consumers of alcohol. This research aimed to compare male and female students in relation to their knowledge and attitudes about alcohol and sexual activity and to identify factors associated with being the victim of alcohol-related non-consensual sex.

Methods

1,110 students completed an online questionnaire. Drinking levels were measured using the Alcohol Use Disorder Identification Test. Non-consensual sexual experiences were measured using the Sexual Experience Survey. Univariate and multivariate analyses were undertaken using chi square and backwards stepwise logistic regression respectively.

Results

A third of respondents had experienced alcohol-related non-consensual sex. Male and female students differed in the importance they gave to cues in deciding if a person wished to have sex with them and their understanding of the law of consent. 82.2% of women who had experienced alcohol-related non-consensual sex were hazardous drinkers compared to 62.9% who drank at lower levels (P < 0.001). Differences existed between men and women, and between those who had and had not experienced alcohol-related non-consensual sex, in relation to assessments of culpability in scenarios depicting alcohol-related intercourse. A third of respondents believed that a significant proportion of rapes were false allegations; significantly more men than women responded in this way.

Conclusions

Alcohol-related coerced sexual activity is a significant occurrence among students; attitudinal and knowledge differences between males and females may explain this. Educational messages that focus upon what is deemed acceptable sexual behaviour, the law and rape myths are needed but are set against a backdrop where drunkenness is commonplace.
In vivo assessment of the host reactions to the biodegradation of the two novel magnesium alloys ZEK100 and AX30 in an animal model
Authors: Huehnerschulte Tim Andreas , Reifenrath Janin , von Rechenberg Brigitte , Dziuba Dina , Seitz Jan Marten , Bormann Dirk , Windhagen Henning , Meyer-Lindenberg Andrea
Published: March 2012

Background

Most studies on biodegradable magnesium implants published recently use magnesium-calcium-alloys or magnesium-aluminum-rare earth-alloys.

However, since rare earths are a mixture of elements and their toxicity is unclear, a reduced content of rare earths is favorable. The present study assesses the in vivo biocompatibility of two new magnesium alloys which have a reduced content (ZEK100) or contain no rare earths at all (AX30).

Methods

24 rabbits were randomized into 4 groups (AX30 or ZEK100, 3 or 6 months, respectively) and cylindrical pins were inserted in their tibiae. To assess the biodegradation μCT scans and histological examinations were performed.

Results

The μCT scans showed that until month three ZEK100 degrades faster than AX30, but this difference is leveled out after 6 months. Histology revealed that both materials induce adverse host reactions and high numbers of osteoclasts in the recipient bone. The mineral apposition rates of both materials groups were high.

Conclusions

Both alloys display favorable degradation characteristics, but they induce adverse host reactions, namely an osteoclast-driven resorption of bone and a subsequent periosteal formation of new bone. Therefore, the biocompatibility of ZEK100 and AX30 is questionable and further studies, which should focus on the interactions on cellular level, are needed.
Taking action on the social determinants of health: improving health access for the urban poor in Mongolia
Authors: Lhamsuren Khandsuren , Choijiljav Tserendolgor , Budbazar Enkhtuya , Vanchinkhuu Surenchimeg , Blanc Diana Chang , Grundy John
Published: March 2012

Introduction

In recent years, the country of Mongolia (population 2.8 million) has experienced rapid social changes associated with economic growth, persisting socio-economic inequities and internal migration. In order to improve health access for the urban poor, the Ministry of Health developed a "Reaching Every District" strategy (RED strategy) to deliver an integrated package of key health and social services. The aim of this article is to present findings of an assessment of the implementation of the RED strategy, and, on the basis of this assessment, articulate lessons learned for equitable urban health planning.

Methods

Principal methods for data collection and analysis included literature review, barrier analysis of health access and in-depth interviews and group discussions with health managers and providers.

Findings

The main barriers to health access for the urban poor relate to interacting effects of poverty, unhealthy daily living environments, social vulnerability and isolation. Implementation of the RED strategy has resulted in increased health access for the urban poor, as demonstrated by health staff having reached new clients with immunization, family planning and ante-natal care services, and increased civil registrations which enable social service provision. Organizational effects have included improved partnerships for health and increased motivation of the health workforce. Important lessons learned from the early implementation of the RED strategy include the need to form strong partnerships among stakeholders at each level of the health system and in the community, as well as the need to develop a specific financing strategy to address the needs of the very poor. The diverse social context for health in an urban poor setting calls for a decentralized planning and partnership strategy, but with central level commitment towards policy guidance and financing of pro-poor urban health strategies.

Conclusions

Lessons from Mongolia mirror other international studies which point to the need to measure and take action on the social determinants of health at the local area level in order to adequately reduce persistent inequities in health care access for the urban poor.
NF-κB as potential target in the treatment of melanoma
Authors: Madonna Gabriele , Ullman Claudio Dansky , Gentilcore Giusy , Palmieri Giuseppe , Ascierto Paolo Antonio
Published: March 2012

The RAS/MAP kinase pathway has attracted attention because activating mutations of the BRAF serine/threonine kinase was described in over 50% of melanomas. Very recently, selective and potent BRAF inhibitors have been developed. Several other signal transduction pathways have been found to be constitutively active or mutated in other subsets of melanoma tumors that are potentially targetable with new agents. Among these, NFκB is another pathway that melanoma tumors use to achieve survival, proliferation and resistance to apoptosis. Inhibition of NF-κB activation appears to be a very promising option for anti-cancer therapies.
Investigation of the interaction between the MIR-503 and CD40 genes in irradiated U937 cells
Authors: Cheng Guanghui , Sun Shilong , Wang Zhanfeng , Jin Shunzi
Published: March 2012

Background

MicroRNAs (miRNAs) are a group of small noncoding RNAs that take part in diverse biological processes by suppressing target gene expression. Relatively few miRNAs have been studied in detail, especially miR-503, and hence the biological relevance of majority remains to be uncovered. Whether altered expression of miRNA-503 affects the immunity response to radiotherapy has yet to be addressed.

Results

In the present study, we applied ionizing radiation with a dose of either 0.1 Gy or 5 Gy to irradiate U937 cells to confirm CD40 as a miR-503 target, which was identified using a bioimformatics tool. In high dose (5 Gy) ionizing-irradiated U937 cells, expression of miR-503 was up regulated while the expression of CD40 gene was down regulated. Using the transfection of the miR-503 gene into U937 cells and Luciferase assay, we confirmed that miR-503 suppressed the expression of CD40, and was a negtive regulator of CD40.

Conclusions

To our knowledge, we are the first to describe involvement of miR-503 in radiobiological effect at a molecular level. This initial finding suggested the evidence that ionizing radiation could alter the expression of miR-503 and its target gene CD40, and may be very important to shed light on a possible mechanism regarding regulation of immune responses to irradiation.
Long term impact of large scale community-directed delivery of doxycycline for the treatment of onchocerciasis
Authors: Tamarozzi Francesca , Tendongfor Nicholas , Enyong Peter A , Esum Mathias , Faragher Brian , Wanji Samuel , Taylor Mark J
Published: March 2012

Background

Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA) strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery.

Findings

Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014) and load (p = 0.012) were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only.

Conclusions

This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to compliment existing control strategies for onchocerciasis, where needed.
Vector-Borne Diseases - constant challenge for practicing veterinarians: recommendations from the CVBD World Forum
Authors: Baneth Gad , Bourdeau Patrick , Bourdoiseau Gilles , Bowman Dwight , Breitschwerdt Edward , Capelli Gioia , Cardoso Luís , Dantas-Torres Filipe , Day Michael , Dedet Jean-Pierre , Dobler Gerhard , Ferrer Lluís , Irwin Peter , Kempf Volkhard , Kohn Babara , Lappin Michael , Little Susan , Maggi Ricardo , Miró Guadalupe , Naucke Torsten , Oliva Gaetano , Otranto Domenico , Penzhorn Banie , Pfeffer Martin , Roura Xavier , Sainz Angel , Shaw Susan , Shin SungShik , Solano-Gallego Laia , Straubinger Reinhard , Traub Rebecca , Trees Alexander , Truyen Uwe , Demonceau Thierry , Fitzgerald Ronan , Gatti Diego , Hostetler Joe , Kilmer Bruce , Krieger Klemens , Mencke Norbert , Mendão Cláudio , Mottier Lourdes , Pachnicke Stefan , Rees Bob , Siebert Susanne , Stanneck Dorothee , Tarancón Mingote Montserrat , von Simson Cristiano , Weston Sarah
Published: March 2012

The human-animal bond has been a fundamental feature of mankind's history for millennia. The first, and strongest of these, man's relationship with the dog, is believed to pre-date even agriculture, going back as far as 30,000 years. It remains at least as powerful today. Fed by the changing nature of the interactions between people and their dogs worldwide and the increasing tendency towards close domesticity, the health of dogs has never played a more important role in family life. Thanks to developments in scientific understanding and diagnostic techniques, as well as changing priorities of pet owners, veterinarians are now able, and indeed expected, to play a fundamental role in the prevention and treatment of canine disease, including canine vector-borne diseases (CVBDs).

The CVBDs represent a varied and complex group of diseases, including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, leishmaniosis, rickettsiosis and thelaziosis, with new syndromes being uncovered every year. Many of these diseases can cause serious, even life-threatening clinical conditions in dogs, with a number having zoonotic potential, affecting the human population.

Today, CVBDs pose a growing global threat as they continue their spread far from their traditional geographical and temporal restraints as a result of changes in both climatic conditions and pet dog travel patterns, exposing new populations to previously unknown infectious agents and posing unprecedented challenges to veterinarians.

In response to this growing threat, the CVBD World Forum, a multidisciplinary group of experts in CVBDs from around the world which meets on an annual basis, gathered in Nice (France) in 2011 to share the latest research on CVBDs and discuss the best approaches to managing these diseases around the world.

As a result of these discussions, we, the members of the CVBD Forum have developed the following recommendations to veterinarians for the management of CVBDs.
Effectiveness of Mindfulness-Based Stress Reduction in Mood, Breast- and Endocrine-Related Quality of Life, and Well-Being in Stage 0 to III Breast Cancer: A Randomized, Controlled Trial
Authors: Hoffman Caroline J. , Ersser Steven J. , Hopkinson Jane B. , Nicholls Peter G. , Harrington Julia E. , Thomas Peter W.
Published: March 2012

Purpose

To assess the effectiveness of mindfulness-based stress reduction (MBSR) for mood, breast- and endocrine-specific quality of life, and well-being after hospital treatment in women with stage 0 to III breast cancer.

Patients and Methods

A randomized, wait-listed, controlled trial was carried out in 229 women after surgery, chemotherapy, and radiotherapy for breast cancer. Patients were randomly assigned to the 8-week MBSR program or standard care. Profile of Mood States (POMS; primary outcome), Functional Assessment of Cancer Therapy–Breast (FACT-B), Functional Assessment of Cancer Therapy–Endocrine Symptoms (FACT-ES) scales and the WHO five-item well-being questionnaire (WHO-5) evaluated mood, quality of life, and well-being at weeks 0, 8, and 12. For each outcome measure, a repeated-measures analysis of variance model, which incorporated week 0 measurements as a covariate, was used to compare treatment groups at 8 and 12 weeks.

Results

There were statistically significant improvements in outcome in the experimental group compared with control group at both 8 and 12 weeks (except as indicated) for POMS total mood disturbance (and its subscales of anxiety, depression [8 weeks only], anger [12 weeks only], vigor, fatigue, and confusion [8 weeks only]), FACT-B, FACT-ES, (and Functional Assessment of Cancer Therapy subscales of physical, social [8 weeks only], emotional, and functional well-being), and WHO-5.

Conclusion

MSBR improved mood, breast- and endocrine-related quality of life, and well-being more effectively than standard care in women with stage 0 to III breast cancer, and these results persisted at three months. To our knowledge, this study provided novel evidence that MBSR can help alleviate long-term emotional and physical adverse effects of medical treatments, including endocrine treatments. MBSR is recommended to support survivors of breast cancer.
Randomized Phase II Trial of Sunitinib on an Intermittent Versus Continuous Dosing Schedule As First-Line Therapy for Advanced Renal Cell Carcinoma
Authors: Motzer Robert J. , Hutson Thomas E. , Olsen Mark R. , Hudes Gary R. , Burke John M. , Edenfield William J. , Wilding George , Agarwal Neeraj , Thompson John A. , Cella David , Bello Akintunde , Korytowsky Beata , Yuan Jinyu , Valota Olga , Martell Bridget , Hariharan Subramanian , Figlin Robert A.
Published: March 2012

Purpose

Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules.

Patients and Methods

Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on the CDD schedule (n = 146) for up to 2 years. The primary end point was time to tumor progression.

Results

Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77; 95% CI, 0.57 to 1.04; P = .090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034).

Conclusion

There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC.
Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers
Authors: Finkelman Brian S. , Rubinstein Wendy S. , Friedman Sue , Friebel Tara M. , Dubitsky Shera , Schonberger Niecee Singer , Shoretz Rochelle , Singer Christian F. , Blum Joanne L. , Tung Nadine , Olopade Olufunmilayo I. , Weitzel Jeffrey N. , Lynch Henry T. , Snyder Carrie , Garber Judy E. , Schildkraut Joellen , Daly Mary B. , Isaacs Claudine , Pichert Gabrielle , Neuhausen Susan L. , Couch Fergus J. , van't Veer Laura , Eeles Rosalind , Bancroft Elizabeth , Evans D. Gareth , Ganz Patricia A. , Tomlinson Gail E. , Narod Steven A. , Matloff Ellen , Domchek Susan , Rebbeck Timothy R.
Published: March 2012

Purpose

Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction.

Methods

Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status.

Results

Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups.

Conclusion

Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.
TET2 Mutations in Acute Myeloid Leukemia (AML): Results From a Comprehensive Genetic and Clinical Analysis of the AML Study Group
Authors: Gaidzik Verena I. , Paschka Peter , Späth Daniela , Habdank Marianne , Köhne Claus-Henning , Germing Ulrich , von Lilienfeld-Toal Marie , Held Gerhard , Horst Heinz-August , Haase Detlef , Bentz Martin , Götze Katharina , Döhner Hartmut , Schlenk Richard F. , Bullinger Lars , Döhner Konstanze
Published: March 2012

Purpose

The tet oncogene family member 2 (TET2) gene was recently identified to be mutated in myeloid disorders including acute myeloid leukemia (AML). To date, there is increasing evidence for a functional role of TET2 mutations (TET2mut) in AML. Thus, we explored the frequency, gene-expression pattern, and clinical impact of TET2mut in a large cohort of patients with AML in the context of other AML-associated aberrations.

Patients and Methods

Samples from 783 younger adult patients with AML were analyzed for the presence of TET2mut (coding exons 3 to 11), and results were correlated with data from molecular genetic analyses, gene-expression profiling, and clinical outcome.

Results

In total, 66 TET2mut were found in 60 patients (60 of 783 patients; 7.6%), including missense (n = 37), frameshift (n = 16), and nonsense (n = 13) mutations, which, with one exception, were all heterozygous. TET2mut were not correlated with distinct clinical features or genetic alterations, except for isocitrate dehydrogenase mutations (IDHmut) that were almost mutually exclusive with TET2mut (P < .001). TET2mut were characterized by only a weak gene-expression pattern, which, nevertheless, reflected TET2mut-associated biology. TET2mut did not impact the response to induction therapy and clinical outcome; the combination of patients who exhibited TET2mut and/or IDHmut revealed shorter overall survival (P = .03), although this association was not independent from known risk factors.

Conclusion

TET2mut were identified in 7.6% of younger adult patients with AML and did not impact the response to therapy and survival. Mutations were mutually exclusive with IDHmut, which supported recent data on a common mechanism of action that might obscure the impact of TET2mut if compared against all other patients with AML.
Optimal Colorectal Cancer Staging Criteria in TNM Classification
Authors: Ueno Hideki , Mochizuki Hidetaka , Akagi Yoshito , Kusumi Takaya , Yamada Kazutaka , Ikegami Masahiro , Kawachi Hiroshi , Kameoka Shingo , Ohkura Yasuo , Masaki Tadahiko , Kushima Ryoji , Takahashi Keiichi , Ajioka Yoichi , Hase Kazuo , Ochiai Atsushi , Wada Ryo , Iwaya Keiichi , Shimazaki Hideyuki , Nakamura Takahiro , Sugihara Kenichi
Published: March 2012

Purpose

Histologic components of the TNM classification system have been repeatedly revised since the fifth edition (TNM5). TNM classification revisions provide different criteria for categorizing tumor nodules without residual lymph node structure (ND). However, there are few systematic evaluations regarding the effectiveness of these revisions.

Patients and Methods

A multicenter pathologic review for ND in colorectal cancer (CRC) was performed. Tumor staging defined by TNM5, sixth edition (TNM6), and seventh edition (TNM7) were compared on the basis of Akaike information criterion (AIC) and Harrell's concordance index (c-index). Moreover, TNM7's prognostic value was compared between the original ND and modified criteria, which considered all regional NDs as lymph node metastasis (LNM) irrespective of the original structure.

Results

In 1,716 treated patients with CRC (1994 to 1998), tumor stages (I/II/III) exhibited better prognoses in TNM7 (AIC, 3055.1; c-index, 0.7215) than in TNM6 (AIC, 3063.7; c-index, 0.7149), but not better than in TNM5 (AIC, 3051.6; c-index, 0.7240). Comparing the original TNM7 and modified criteria, 4.2% of patients were classified in different N stages (N0/N1/N2a/N2b); both AIC and the c-index were superior in the modified criteria (AIC, 3029.40; c-index, 0.7271) compared with the original criteria (AIC, 3040.58; c-index, 0.7230). Modified criteria were also associated with improved prognostic power of tumor stages (I/IIA/IIB/IIC/IIIA/IIIB/IIIC). These results were similar in another cohort of 2,242 treated patients with CRC (1999 to 2003).

Conclusion

The prognostic value of TNM7 is better than that of TNM6; however, improvement over TNM5 is insignificant. By considering all regional NDs as LNM irrespective of their morphology, TNM classification can be simplified and its prognostic value improved.
Diverse roles for VEGF-A in the nervous system
Authors: Mackenzie Francesca , Ruhrberg Christiana
Published: March 2012

Vascular endothelial growth factor A (VEGF-A) is best known for its essential roles in blood vessel growth. However, evidence has emerged that VEGF-A also promotes a wide range of neuronal functions, both in vitro and in vivo, including neurogenesis, neuronal migration, neuronal survival and axon guidance. Recent studies have employed mouse models to distinguish the direct effects of VEGF on neurons from its indirect, vessel-mediated effects. Ultimately, refining our knowledge of VEGF signalling pathways in neurons should help us to understand how the current use of therapeutics targeting the VEGF pathway in cancer and eye disease might be expanded to promote neuronal health and nerve repair.
Development of the social brain in adolescence
Authors: Blakemore Sarah-Jayne
Published: March 2012

The brain has evolved to understand and interact with other people. We are increasingly learning more about the neurophysiological basis of social cognition and what is known as the social brain, that is the network of brain regions involved in understanding others. This paper focuses on how the social brain develops during adolescence. Adolescence is a time characterized by change – hormonally, physically, psychologically and socially. Yet until recently this period of life was neglected by cognitive neuroscience. In the past decade, research has shown that the brain develops both structurally and functionally during adolescence. Large-scale structural MRI studies have demonstrated development during adolescence in white matter and grey matter volumes in regions within the social brain. Activity in some of these regions, as measured using fMRI, also shows changes between adolescence and adulthood during social cognition tasks. I will also present evidence that theory of mind usage is still developing late in adolescence. Finally, I will speculate on potential implications of this research for society.
Absence of the right iliac vein and an unusual connection between both common femoral veins
Authors: Yahyayev A , Bulakci M , Yilmaz E , Ucar A , Sayin O A , Yekeler E
Published: March 2012

The aim of the study is to report a case of a rare congenital anomaly of the venous system and to emphasize its clinical importance. We describe a case of aplasia of the right common and external iliac veins in a healthy seven-year-old boy who was referred for Doppler ultrasound examination for further evaluation of an abnormal varicosity in the suprapubic region. Colour Doppler ultrasound revealed a dilated, arch-shaped vein. Contrast-enhanced magnetic resonance angiography showed the absence of the right common iliac vein and external iliac vein. It also clearly demonstrated the aberrant venous structure, originating from the right common femoral vein and draining to the left common femoral vein. In conclusion, in our case, the patient's life was threatened because the aberrant venous connection crossing within subcutaneous fatty tissue was not protected from external trauma and possible abdominal surgical interventions. Additional attention should be given to avoid such injuries, which can cause significant haemorrhage.
Autologous chondrocyte implantation for osteochondral lesions in the knee using a bilayer collagen membrane and bone graft
Authors: Vijayan S. , Bartlett W. , Bentley G. , Carrington R. W. J. , Skinner J. A. , Pollock R. C. , Alorjani M. , Briggs T. W. R.
Published: March 2012

Matrix-induced autologous chondrocyte implantation (MACI) is an established technique used to treat osteochondral lesions in the knee. For larger osteochondral lesions (> 5 cm2) deeper than approximately 8 mm we have combined the use of two MACI membranes with impaction grafting of the subchondral bone. We report our results of 14 patients who underwent the ‘bilayer collagen membrane’ technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There were 12 men and two women with a mean age of 23.6 years (16 to 40). The mean size of the defect was 7.2 cm2(5.2 to 12 cm2) and were located on the medial (ten) or lateral (four) femoral condyles. The mean modified Cincinnati knee score improved from 45.1 (22 to 70) pre-operatively to 82.8 (34 to 98) at the most recent review (p < 0.05). The visual analogue pain score improved from 7.3 (4 to 10) to 1.7 (0 to 6) (p < 0.05). Twelve patients were considered to have a good or excellent clinical outcome. One graft failed at six years.

The BCMT resulted in excellent functional results and durable repair of large and deep osteochondral lesions without a high incidence of graft-related complications.
A prospective clinical and radiological study comparing hydroxyapatite-coated with cemented tibial components in total knee replacement
Authors: Bercovy M. , Beldame J. , Lefebvre B. , Duron A.
Published: March 2012

This prospective study compares the outcome of 157 hydroxyapatite (HA)-coated tibial components with 164 cemented components in the ROCC Rotating Platform total knee replacement in 291 patients. The mean follow-up was 7.6 years (5.2 to 11). There were two revisions for loosening: one for an HA-coated and one for a cemented tibial component. Radiological evaluation demonstrated no radiolucent lines with the HA-coated femoral components. A total of three HA-coated tibial components exhibited radiolucent lines at three months post-operatively and these disappeared after three further months of protected weight-bearing. With HA-coated components the operating time was shorter (p <  0.006) and the radiological assessment of the tibial interface was more stable (p < 0.01). Using revision for aseptic loosening of the tibial component as the end point, the survival rates at nine years was identical for both groups at 99.1%.

Our results suggest that HA-coated components perform at least as well as the same design with cemented components and compare favourably with those of series describing cemented or porous-coated knee replacements, suggesting that fixation of both components with hydroxyapatite is a reliable option in primary total knee replacement.
The development of fibronectin-functionalised hydroxyapatite coatings to improve dermal fibroblast attachmentin vitro
Authors: Pendegrass C. J. , El-Husseiny M. , Blunn G. W.
Published: March 2012

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.
The World Health Organization ‘5 Moments of Hand Hygiene’
Authors: Chou D. T. S. , Achan P. , Ramachandran M.
Published: March 2012

The World Health Organization (WHO) launched the first Global Patient Safety Challenge in 2005 and introduced the ‘5 moments of hand hygiene’ in 2009 in an attempt to reduce the burden of health care associated infections. Many NHS trusts in England adopted this model of hand hygiene, which prompts health care workers to clean their hands at five distinct stages of caring for the patient. Our review analyses the scientific foundation for the five moments of hand hygiene and explores the evidence, as referenced by WHO, to support these recommendations. We found no strong scientific support for this regime of hand hygiene as a means of reducing health care associated infections. Consensus-based guidelines based on weak scientific foundations should be assessed carefully to prevent shifting the clinical focus from more important issues and to direct limited resources more effectively.

We recommend caution in the universal adoption of the WHO ‘5 moments of hand hygiene’ by orthopaedic surgeons and other health care workers and emphasise the need for evidence-based principles when adopting hospital guidelines aimed at promoting excellence in clinical practice.
Zona conoidea of the elbow
Authors: Jeon I-H. , Chun J-M. , Lee C-S. , Yoon J-O. , Kim P-T. , An K-N. , Morrey B. F. , Shin H-D.
Published: March 2012

The zona conoidea comprises the area of the lateral trochlear ridge of the humerus. The purpose of this study is to reintroduce this term ‘zona conoidea’ to the discussion of the human elbow and to investigate its significance in the development of osteoarthritis of the elbow.

The upper extremities of 12 cadavers were prepared. With the forearm in neutral, pronation and supination, the distance between the bevel of the radial head and zona conoidea was inspected. A total of 12 healthy volunteers had a CT scan. The distance between the zona conoidea and the bevelled rim of the radial head was measured in these positions.

In the anatomical specimens, early osteo-arthritic changes were identified in the posteromedial bevelled rim of the radial head, and the corresponding zona conoidea in supination. Measurement in the CT study showed that in full supination, the distance between the bevel of the radial head and the zona conoidea was at a minimum.

This study suggests that the significant contact between the bevel of the radial head and the zona conoidea in supination is associated with the initiation of osteoarthritis of the elbow in this area.
Hip resurfacing with femoral osteotomy for painful subluxed or dislocated hips in patients with cerebral palsy
Authors: Prosser G. H. , Shears E. , O’Hara J. N.
Published: March 2012

The painful subluxed or dislocated hip in adults with cerebral palsy presents a challenging problem. Prosthetic dislocation and heterotopic ossification are particular concerns. We present the first reported series of 19 such patients (20 hips) treated with hip resurfacing and proximal femoral osteotomy. The pre-operative Gross Motor Function Classification System (GMFCS) was level V in 13 (68%) patients, level IV in three (16%), level III in one (5%) and level II in two (11%). The mean age at operation was 37 years (13 to 57).

The mean follow-up was 8.0 years (2.7 to 11.6), and 16 of the 18 (89%) contactable patients or their carers felt that the surgery had been worthwhile. Pain was relieved in 16 of the 18 surviving hips (89%) at the last follow-up, and the GMFCS level had improved in seven (37%) patients. There were two (10%) early dislocations; three hips (15%) required revision of femoral fixation, and two hips (10%) required revision, for late traumatic fracture of the femoral neck and extra-articular impingement, respectively. Hence there were significant surgical complications in a total of seven hips (35%). No hips required revision for instability, and there were no cases of heterotopic ossification.

We recommend hip resurfacing with proximal femoral osteotomy for the treatment of the painful subluxed or dislocated hip in patients with cerebral palsy.
Nerve injuries sustained during warfare
Authors: Birch R. , Misra P. , Stewart M. P. M. , Eardley W. G. P. , Ramasamy A. , Brown K. , Shenoy R. , Anand P. , Clasper J. , Dunn R. , Etherington J.
Published: March 2012

We describe 261 peripheral nerve injuries sustained in war by 100 consecutive service men and women injured in Iraq and Afghanistan. Their mean age was 26.5 years (18.1 to 42.6), the median interval between injury and first review was 4.2 months (mean 8.4 months (0.36 to 48.49)) and median follow-up was 28.4 months (mean 20.5 months (1.3 to 64.2)). The nerve lesions were predominantly focal prolonged conduction block/neurapraxia in 116 (45%), axonotmesis in 92 (35%) and neurotmesis in 53 (20%) and were evenly distributed between the upper and the lower limbs. Explosions accounted for 164 (63%): 213 (82%) nerve injuries were associated with open wounds. Two or more main nerves were injured in 70 patients. The ulnar, common peroneal and tibial nerves were most commonly injured. In 69 patients there was a vascular injury, fracture, or both at the level of the nerve lesion. Major tissue loss was present in 50 patients: amputation of at least one limb was needed in 18. A total of 36 patients continued in severe neuropathic pain.

This paper outlines the methods used in the assessment of these injuries and provides information about the depth and distribution of the nerve lesions, their associated injuries and neuropathic pain syndromes.
Corrigenda/Errata
Authors: Scott J.
Published: March 2012

Thomas WJ, Jenkins EF, Owen JM, Sangster MJ, Kirubanandan R, Beynon C, Woods DA. Treatment of frozen shoulder by manipulation under anaesthetic and injection: does the timing of treatment affect the outcome? J Bone Joint Surg [Br] 2011;93-B:1377-81. doi: 10.1302/0301-620X.93B10.27224.
Legal Framework for the Single Window Concept in ASEAN: A Successful Movement towards Trade Facilitation in East Asian Countries
Authors: Weber Rolf H.
Published: March 2012

The Single Window concept refers to an «exchange» facility that allows parties involved in trade and transport to lodge standardized information and documents with a single entry point to fulfill all import, export, and transit-related regulatory requirements. The implementation and use of up-to-date Information and Communication Technologies (ICT) facilitates trade and a Single Window should lead to a close co-operation between all involved governmental authorities and agencies as well as the trading community.
A Bottom-Up Approach for Climate Change: The Trade Experience
Authors: Leal-Arcas Rafael
Published: March 2012

This article argues that the Kyoto Protocol to the 1992 Framework Convention on Climate Change was doomed to face difficulties ab initio. Moving the climate change agenda forward multilaterally among the 195 parties to the United Nations Framework Convention on Climate Change (UNFCCC) is proving to be a serious challenge. The lack of progress in UNFCCC negotiations in recent years, especially the failure to obtain an international agreement on emissions limitations targets and timetables by all major developed and developing country emitters, has led many to question whether the UNFCCC is, in fact, the best and most effective forum for mobilizing a global response to climate change. The current approach to negotiating a comprehensive, universal, and legally binding global agreement on climate change is unlikely to succeed. The article concludes that no breakthroughs will take place regarding a global climate change agreement until there is more political maturity on the side of the U.S., and until rapidly emerging economies such as China and India indicate that they are ready to play their part in tackling the climate change challenge, since they are part of the solution. Large emitters of GHG need to be involved for negotiations to come to a conclusion. Much progress is still needed until we reach an international agreement that covers all the world’s countries and that is strong enough to tackle climate change effectively and is equitable enough to gain the sympathy of all countries.
A fluorescence correlation spectroscopy-based enzyme assay for human Dicer
Authors: Werner Arne , Skakun Victor V. , Ziegelmüller Patrick , Hahn Ulrich
Published: March 2012

Here, we present an in vitro assay based on fluorescence correlation spectroscopy (FCS), which allows investigation of the kinetic behaviour of human Dicer. The assay is based on the different mobilities of substrate and product. The change of substrate mobility was independent of the choice of the fluorescence label, allowing exclusion of non-specific photophysical artefacts. Dicer and RNase III cleavage led to different product diffusion times. Single-stranded RNA did not change its mobility after cleavage by both double-strand-specific RNases. In agreement with the literature, the RNase activity of Dicer could be inhibited by substituting Ca2+ for Mg2+. In a defined system of two diffusion species of similar label and mobility differences, such as substrate and product, the linearity of the assay could be proven. An FCS-based enzyme assay is proposed, which allows monitoring of Dicer activity with high specificity in vitro.
Diskrepanzbasierte Regelung der kontinuierlichen Kristallisation
Authors: Palis Stefan , Kienle Achim
Published: March 2012

Der Beitrag beschreibt einen neuen Regelungsansatz zur Stabilisierung von Kristallisatoren. Es ist bekannt, dass diese in Verbindung mit einer Feinkornauflösung zu Instabilitäten und dem Auftreten von unerwünschten Oszillationen neigen. Modelle für Kristallisatoren bestehen meist aus einer nichtlinearen partiellen Integrodifferentialgleichung, der Populationsbilanz für die Kristallgrößenverteilung, gekoppelt mit einer gewöhnlichen Differentialgleichung zur Beschreibung der flüssigen Phase, was einen rigorosen Reglerentwurf vor erhebliche Probleme stellt. Deshalb wird im Rahmen dieser Arbeit auf ein Stabilitätskonzept zurückgegriffen, welches Aussagen über die Stabilität eines Prozesses bezüglich zweier verallgemeinerter Abstandmaße, den sogenannten Diskrepanzen, erlaubt.
Reverse Code Engineering — State of the Art and Countermeasures
Authors: Willems Carsten , Freiling Felix C.
Published: March 2012

Reverse Code Engineering (RCE) is, loosely speaking, the process of analyzing a piece of code in order to understand it. RCE is often used to analyze proprietary, binary programs, and in the last few years this research area has evolved a lot. In this article, we survey and structure the area of reverse code engineering. We focus on different techniques to recover both the control and data flow of a given binary program, for which no source code is available. Furthermore, we also discuss analysis techniques for malicious software (short: malware), which is commonly protected to resist analysis. We present the current state of the art of such protection techniques, while dividing them into active and passive measures. Our survey focusses on reverse engineering of binary native code for the Intel/AMD x86 architecture, and we thus disregard analysis of byte-code like Java or .NET. Nevertheless, most of the techniques presented in this article can be transferred to other architectures and operating system as well.
Platform-Independent Recognition of Procedures in Binaries Based on Simple Characteristics
Authors: Eschweiler Sebastian , Gerhards-Padilla Elmar
Published: March 2012

Malware analysts are more and more overstrained by today´s flood of malware. Hence, the need for automated tools to assist malware analysis becomes apparent. A common approach of malware analysis is reverse engineering its components, namely (sub-)procedures. We present and evaluate simple procedure characteristics such as the number of instructions for their robustness with respect to different compilers, compilation options and even across operating systems. We identify robust characteristics and apply standard machine learning algorithms based on these characteristics to automatically identify already known procedures in new malware. This prevents analysts from repeatedly reversing known procedures.
Modeling and Describing Misuse Scenarios Using Signature-Nets and Event Description Language
Authors: Flegel Ulrich , Meier Michael
Published: March 2012

In the area of intrusion detection the misuse detection approach assumes that relevant activity violating security policies is known a priori and it provides for fast intrusion detection with low false alarm rate, thereby complementing the anomaly detection approach. Hence, misuse detection is an indispensable ingredient to a suitable strategy for intrusion detection. Misuse detection calls for a comprehensive framework for modeling and analysing attack activity. This contribution presents the highly expressive and modular Signature-net framework. Signature-nets allow for visual modeling and simulation of attack detection signatures, as well as for formal analysis. The framework lends itself to highly optimized implementation and may be flexibly deployed, e. g., for network-based and host-based intrusion detection or alarm correlation.