bluuebunny/crossref_metadata_2025 huggingface dataset:
The reliability, precision and clinically meaningful change of walking assessments in multiple sclerosis
Authors: Learmonth Yvonne C , Dlugonski Deirdre D , Pilutti Lara A , Sandroff Brian M , Motl Robert W
Published: April 2013

Background:

Assessing walking impairment in those with multiple sclerosis (MS) is common, however little is known about the reliability, precision and clinically important change of walking outcomes.

Objective:

The purpose of this study was to determine the reliability, precision and clinically important change of the Timed 25-Foot Walk (T25FW), Six-Minute Walk (6MW), Multiple Sclerosis Walking Scale-12 (MSWS-12) and accelerometry.

Methods:

Data were collected from 82 persons with MS at two time points, six months apart. Analyses were undertaken for the whole sample and stratified based on disability level and usage of walking aids. Intraclass correlation coefficient (ICC) analyses established reliability: standard error of measurement (SEM) and coefficient of variation (CV) determined precision; and minimal detectable change (MDC) defined clinically important change.

Results:

All outcome measures were reliable with precision and MDC varying between measures in the whole sample: T25FW: ICC=0.991; SEM=1 s; CV=6.2%; MDC=2.7 s (36%), 6MW: ICC=0.959; SEM=32 m; CV=6.2%; MDC=88 m (20%), MSWS-12: ICC=0.927; SEM=8; CV=27%; MDC=22 (53%), accelerometry counts/day: ICC=0.883; SEM=28450; CV=17%; MDC=78860 (52%), accelerometry steps/day: ICC=0.907; SEM=726; CV=16%; MDC=2011 (45%). Variation in these estimates was seen based on disability level and walking aid.

Conclusion:

The reliability of these outcomes is good and falls within acceptable ranges. Precision and clinically important change estimates provide guidelines for interpreting these outcomes in clinical and research settings.
Implementation of a Telehealth Programme for Patients with Severe Chronic Obstructive Pulmonary Disease Treated with Long-Term Oxygen Therapy
Authors: Jódar-Sánchez Francisco , Ortega Francisco , Parra Carlos , Gómez-Suárez Cristina , Jordán Ana , Pérez Pablo , Bonachela Patricia , Leal Sandra , Barrot Emilia
Published: April 2013

We conducted a pilot study of the effectiveness of home telehealth for patients with advanced chronic obstructive pulmonary disease treated with long-term oxygen therapy. Patients were randomized into a telehealth group (n = 24) and a control group (n = 21) who received usual care. Patients in the telehealth group measured their vital signs on weekdays and performed spirometry on two days per week. The data were transmitted automatically to a clinical call centre. After four months of monitoring the mean number of accident and emergency department visits in the telehealth group was slightly lower than in the control group (0.29 versus 0.43, P = 0.25). The mean number of hospital admissions was 0.38 in the telehealth group and 0.14 in the control group ( P = 0.47). During the study a total of 40 alerts were detected. The clinical triage process detected eight clinical exacerbations which were escalated by the case manager for a specialist consultation. There were clinically important differences in health-related quality of life in both groups. The mean score on the SGRQ was 10.9 versus 4.5 in the control group (P = 0.53). The EuroQol-5D score improved by 0.036 in the telehealth group and by 0.003 in the control group ( P = 0.68). Both patients and healthcare professionals showed a high level of satisfaction with the telehealth programme.
A Randomised Controlled Trial of an Sms-Based Mobile Epilepsy Education System
Authors: Lua Pei Lin , Neni Widiasmoro Selamat
Published: April 2013

We evaluated an epilepsy education programme based on text messaging (SMS). Epilepsy outpatients from three hospitals in Malaysia were randomised into two groups: intervention and control. Patients in the control group were supplied with printed epilepsy educational material while those in the intervention group also received text messages from the Mobile Epilepsy Educational System (MEES). A total of 136 patients completed the study (mean age 31 years; 91% Malay; 51% with an illness duration of more than 5 years). A between-group analysis showed that the awareness, knowledge and attitudes (AKA) about epilepsy did not significantly differ between the groups at baseline ( P > 0.05). The intervention patients reported better AKA levels during follow-up compared to the control patients ( P < 0.05). A within-group analysis showed that in intervention patients, there were significant improvements in all AKA domains with larger effect sizes ( P < 0.01) while control patients also exhibited significant improvement in most domains except for Awareness but with smaller effect sizes. After controlling for possible confounding variables (age, gender, educational qualification, monthly income and baseline mean for each domain), the intervention group still reported significantly higher AKA than the control group particularly in Awareness ( P < 0.001) and Total AKA ( P = 0.003). There was also significantly better medication adherence and clinic attendance in the intervention group ( P < 0.05). The results suggest that the addition of the MEES to conventional epilepsy education is effective in improving AKA.
Telephone Follow-Up for the Management of Thyrotoxicosis: A Patient Satisfaction Survey
Authors: Davies Charlotte , Vas Prashanth , Oyibo Samson O
Published: April 2013

We conducted a postal survey to assess patient satisfaction with our use of telephone follow-up for the management of thyrotoxicosis. Patients were asked to answer nine questions using the five-point Likert scale. They could also make comments and suggestions for improvement. Over a 17-month period, 135 patients with thyrotoxicosis were followed up by telephone (32 males and 103 females, aged 17–85 years). Eighty-two completed questionnaires were returned (61% response rate). More than 90% of responders strongly agreed or agreed that they were comfortable with telephone follow-up, that it saved them time, that it met their needs and that they would use the telephone follow-up service again. Twelve percent of responders felt that telephone follow-up was not as good as conventional face-to-face consultation. The survey shows that the use of telephone follow-up for the management of thyrotoxicosis is acceptable to most patients, as long as it is mixed with face-to-face consultations.
A Pilot Trial of the Ipad Tablet Computer as a Portable Device for Visual Acuity Testing
Authors: Zhang Zhao-Tian , Zhang Shao-Chong , Huang Xiong-Gao , Liang Ling-Yi
Published: April 2013

We evaluated the accuracy of an app for the iPad tablet computer (Eye Chart Pro) as a portable method of visual acuity (VA) testing. A total of 120 consecutive patients (240 eyes) underwent visual acuity test with an iPad 2 and a conventional light-box chart. The logMAR VA results from the iPad were significantly higher than those from the light-box ( P < 0.001). Bland-Altman analysis revealed a mean difference (bias) of 0.02 logMAR units between the VA results from the iPad chart and the light-box chart, with 95% limits of agreement of −0.14 to 0.19. Two groups of patients were defined: in Group 1 there were 182 eyes with VA better than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 0.54 and by the light-box chart it was 0.52; there was no significant difference between them ( P = 0.69). In Group 2 there were 58 eyes with VA equal to or worse than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 1.26 and was 1.10 by the light box; the result from the iPad was significantly lower ( P < 0.001). The Eye Chart Pro app installed on the iPad is reliable for VA testing only when the Snellen VA is better than 0.1 (20/200).
The effects of explosion on the musculoskeletal system
Authors: Ramasamy Arul , Hughes Anna , Carter Nicholas , Kendrew Jon
Published: April 2013

Explosions remain the leading cause of death and injury to combatants in conflict. The current ‘Global War on Terror’ has resulted in a shift of explosive-related injuries from the battlefield into civilian centres. Despite musculoskeletal injuries being the most common injury witnessed in blast, there remains little research into the effects of blast on this system. In order to develop new treatment regimens and mitigation systems, there is a requirement to have a better understanding of skeletal trauma in this unique environment. The aim of this review article is to deconstruct the complex injury mechanisms witnessed in blast and relate them to its effects on the musculoskeletal system.
Competing models of journalism? Political affairs coverage in US, British, German, Swiss, French and Italian newspapers
Authors: Esser Frank , Umbricht Andrea
Published: April 2013

A content analysis of 6525 randomly sampled political news stories from national, regional and weekly newspapers in six western countries between 1960 and today examines to which degree discursively defined reporting styles correspond to conceptual typologies of media systems and historical classifications of journalistic traditions. Univariate and multivariate analyses of three key indicators (opinion-orientation, objectivity, negativity) reveal three approaches to newsmaking: a US-led model of rational news analysis, an Italian-led model of polarized reporting, and a Germanic model of disseminating news with views. Merging a historically informed institutionalist approach with systematic content analysis, the study’s main contribution to comparative communication research is to clarify our understanding of divergent models of journalism, contextualize existing media-system typologies, and revise assumptions about the affiliation of individual systems to certain models.
Political orientation and the resonance of ethnic mobilization: Understanding the prospects for reducing ethnic politics in Fiji
Authors: Larson Erik
Published: April 2013

How do attempts to politically mobilize support on the basis of ethnicity resonate with the people targeted? This paper develops theory about the affinities between institutionalized political orientations—how individuals understand their place in political processes and how they make decisions about political issues—and the ways that ethnic appeals may make sense to people. By focusing on institutionalized orientations as a form of consciousness, this theory enables analysis of how orientations of different segments of a polity facilitate the resonance of ethnic appeals and relate to one another, which holds implications for attempts to counter ethnic mobilization. The paper applies this theory to Fiji, a country that has experienced divisive ethnic politics and attempts to forge alternate models of national unity. Based on in-depth interviews with a sample of citizens from across Fiji, I conclude that distinct political orientations characterize different parts of the population and find within-orientation differences between those who understand political developments in more ethnic terms and those who do not. Using this evidence, I draw implications about the types of changes that might transform the resonance of ethnic mobilization in Fiji.
The impact of reasons for attending university on academic resourcefulness and adjustment
Authors: Kennett Deborah J , Reed Maureen J , Stuart Amanda S
Published: April 2013

It is a well-known phenomenon that generally resourceful students are more likely to employ specific self-control skills, such as academic resourcefulness, to overcome stressors in their life, and as a result, are more likely to be better adjusted, to receive higher grades, and to remain in university than their less resourceful counterparts. To what extent the reasons students attend university further explains academic resourcefulness and why some students fail to persevere with academic challenges were examined in this study. A sample of 481 undergraduate students completed scales assessing general and academic resourcefulness, academic self-efficacy, explanatory style, university adaptation, and reasons for attending university. Students were also asked questions concerning retention, and expected and past grade performance. The results showed that students attending university for more internal reasons and less so to please others and to delay responsibilities uniquely contributed to higher levels of academic resourcefulness. Insight as to why some students may attribute academic failure to lack of effort and personal ability, be less adjusted, decide to leave university, and be expecting and attaining lower grades is provided.
Grip and pinch strength: Normative data for healthy Indian adults
Authors: Mullerpatan Rajani P , Karnik Gayatri , John Rebecca
Published: April 2013

Introduction

Normative values of grip and pinch strength are used to determine the effect of treatment, to assess patients’ initial limitation and provide a baseline for re-assessment of patient progress. Data gathered from western populations cannot be used for reference in Indian populations due to variations in genetic, environmental and nutritional factors.

Methods

A convenience sample of 1005 healthy adults was recruited for this descriptive study. Grip and pinch strength were measured with elbow positioned at 0°, 45°, 90° and full elbow flexion using a JAMAR dynamometer and B&L Pinch gauge.

Results

Men presented significantly higher values for grip strength ( p ≤ 0.001) at 0° of elbow flexion (37.8 kg) than women (22.12 kg). For remaining positions of the elbow, average grip strength values in men were 33 kg and in women were 20 kg. Men presented significantly higher values of tip, palmar and key pinch (3.9, 6.7 and 7.2 kg) than women (3.2, 4.71 and 4.81 kg). Grip strength was significantly different at different positions of the elbow ( p ≤ 0.001); it was highest at 0° and lowest at 135° of elbow flexion among men.

Conclusions

Findings from study will provide reference values for grip, tip, palmar and key pinch strength for healthy Indian adults. Grip and pinch strength of healthy Indian adults is less compared with age and gender-matched population from other continents.
Scaling Irrational Beliefs in the General Attitude and Belief Scale
Authors: Owings Lindsay R. , Thorpe Geoffrey L. , McMillan Elaine S. , Burrows Rachel D. , Sigmon Sandra T. , Alley Dorothy C.
Published: April 2013

Accurate measurement of key constructs is essential to the continued development of Rational-Emotive Behavior Therapy (REBT). The General Attitude and Belief Scale (GABS), a contemporary inventory of rational and irrational beliefs based on current REBT theory, is one of the most valid and widely used instruments available, and recent research has continued to improve its psychometric standing. In this study of 544 students, item response theory (IRT) methods were used (a) to identify the most informative item in each irrational subscale of the GABS, (b) to determine the level of irrationality represented by each of those items, and (c) to suggest a condensed form of the GABS for further study with clinical populations. Administering only the most psychometrically informative items to clients could result in economies of time and effort. Further research based on the scaling of items could clarify the specific patterns of irrational beliefs associated with particular clinical syndromes.
Pan-Africanism
Authors: Guevara Raul Diaz
Published: April 2013

This essaic-article goes against established conventions that there is anything ethno-cultural (and hence national) about the so-called African tribes. Drawing largely from the culture history of precolonial/prepolitical Africans—that is, the Bantu/Cushitic-Ethiopians (Azanians)—the author has demonstrated vividly that far from being distinct ethno-culture national communities, the so-called tribes of African states are better considered subculture groups, whose regional culture practices erstwhile paid tribute to their nation’s main culture center in Karnak. For example, using the culture symbols and practices of some local groups and linking them to the predynastic and dynastic Pharaonic periods, I argued that there is compelling evidence against qualifying Africa’s tribes as distinct ethno-culture national entities. In genuine culture context, I stressed that the Ritual of Resurrection and its twin culture process of the mummification of deceased indigenous Pharaohs tend to suggest that the object of the Bantu/Cushitic-Ethiopians national culture was life (in its eternal manifestation) and then resurrection later, and that there are recurring (culturally sanctioned) ethical examples among the culture custodians of these subculture groups that generally pay tribute to the overarching culture norm. Furthermore, the fact that the Ritual of Resurrection began in the Delta region and ended at the Sources of the Nile, where the spirit of the deceased indigenous Pharaohs was introduced into the spiritual world of their ancestors, contradicts conventional perceptions that ancient Egypt was a distinct national community isolated from precolonial/prepolitical Africa/Azania.
The Acute Care Physical Therapy HIV/AIDS Patient Population
Authors: Kinirons Stacy A. , Do Sandy
Published: April 2013

This study was based on an analysis of an existing database compiled from 475 medical records of people living with HIV/AIDS admitted to an acute-care hospital in New York City in 2004. The characteristics of patients with HIV infection that received physical therapy were determined. Differences between patients with HIV infection that did and did not receive physical therapy, as well as predictors of receipt of physical therapy, were identified. The physical therapy subgroup (n = 69) had a mean age of 48.3 years, consisted of more men than women, and was predominately black, with public health insurance. Admissions were commonly due to non-AIDS-defining illness as the primary diagnoses, accompanied by several comorbidities. Admissions often presented with functional deficits, incurred a prolonged length of stay, and required assistance at discharge. Differences existed between the physical therapy subgroup and the non-physical therapy subgroup (n = 406). Predictors of receipt of physical therapy were functional status on admission and length of stay.
The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial
Authors: Hunt Peter W. , Shulman Nancy S. , Hayes Timothy L. , Dahl Viktor , Somsouk Ma , Funderburg Nicholas T. , McLaughlin Bridget , Landay Alan L. , Adeyemi Oluwatoyin , Gilman Lee E. , Clagett Brian , Rodriguez Benigno , Martin Jeffrey N. , Schacker Timothy W. , Shacklett Barbara L. , Palmer Sarah , Lederman Michael M. , Deeks Steven G.
Published: April 2013

Key Points

Maraviroc intensification unexpectedly increases T-cell activation in peripheral blood and rectal mucosa during treated HIV infection. Maraviroc appears to redistribute CD8+ T cells from the gut to peripheral blood during treated HIV infection.
Interleukin-7 promotes HIV persistence during antiretroviral therapy
Authors: Vandergeeten Claire , Fromentin Rémi , DaFonseca Sandrina , Lawani Mariam B. , Sereti Irini , Lederman Michael M. , Ramgopal Moti , Routy Jean-Pierre , Sékaly Rafick-Pierre , Chomont Nicolas
Published: April 2013

Key Points

IL-7 does not disrupt viral latency in highly pure resting latently infected CD4+ T cells from HIV-infected subjects receiving ART. IL-7 therapy leads to a 70% increase in the absolute number of circulating CD4+ T cells harboring integrated HIV DNA 4 weeks posttherapy.
A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia
Authors: Petersdorf Stephen H. , Kopecky Kenneth J. , Slovak Marilyn , Willman Cheryl , Nevill Thomas , Brandwein Joseph , Larson Richard A. , Erba Harry P. , Stiff Patrick J. , Stuart Robert K. , Walter Roland B. , Tallman Martin S. , Stenke Leif , Appelbaum Frederick R.
Published: April 2013

Key Points

The addition of gemtuzumab ozogamicin to induction or maintenance therapy failed to improve the complete response rate or overall survival in patients with acute myeloid leukemia.
Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients
Authors: Shi Yeen Tiffany Ng , Pathmanathan Rajadurai , Shiran Mohd Sidik , Ahmad Zaid Fattah Azman , Cheah Yoke Kqueen
Published: April 2013

Background

Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.

Results

All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.

Conclusions

Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.
Cancer physicians’ attitude towards treatment of the elderly cancer patient in a developed Asian country
Authors: Pang Angela , Ho Shirlynn , Lee Soo-Chin
Published: April 2013

Background

With an aging population and an increasing number of elderly patients with cancer, it is essential for us to understand how cancer physicians approach the management and treatment of elderly cancer patients as well as their methods of cancer diagnosis disclosure to older versus younger patients in Singapore, where routine geriatric oncology service is not available.

Methods

57 cancer physicians who are currently practicing in Singapore participated in a written questionnaire survey on attitudes towards management of the elderly cancer patient, which included 2 hypothetical clinical scenarios on treatment choices for a fit elderly patient versus that for a younger patient.

Results

The participants comprised of 68% medical oncologists, 18% radiation oncologists, and 14% haematologists. Most physicians (53%) listed performance status (PS) as the top single factor affecting their treatment decision, followed by cancer type (23%) and patient’s decision (11%). The top 5 factors were PS (95%), co-morbidities (75%), cancer stage (75%), cancer type (75%), patient’s decision (53%), and age (51%). 72% of physicians were less likely to treat a fit but older patient aggressively; 53% and 79% opted for less intensive treatments for older patients in two clinical scenarios of lymphoma and early breast cancer, respectively. 37% of physicians acknowledged that elderly cancer patients were generally under-treated.

Only 9% of physicians chose to disclose cancer diagnosis directly to the older patient compared to 61% of physicians to a younger patient, citing family preference as the main reason. Most participants (61%) have never engaged a geriatrician’s help in treatment decisions, although the majority (90%) would welcome the introduction of a geriatric oncology programme.

Conclusions

Advanced patient age has a significant impact on the cancer physician’s treatment decision-making process in Singapore. Many physicians still accede to family members’ request and practice non-disclosure of cancer diagnosis to geriatric patients, which may pose as a hurdle to making an informed decision regarding management for the geriatric cancer patients. Having a formal geriatric oncology programme in Singapore could potentially help to optimize the management of geriatric oncology patients.
Oral intake of phenylbutyrate with or without vitamin D3upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis
Authors: Mily Akhirunnesa , Rekha Rokeya Sultana , Kamal S M Mostafa , Akhtar Evana , Sarker Protim , Rahim Zeaur , Gudmundsson Gudmundur H , Agerberth Birgitta , Raqib Rubhana
Published: April 2013

Background

We earlier showed that 4-phenylbutyrate (PB) can induce cathelicidin LL-37 expression synergistically with 1,25-dihydroxyvitamin D3 in a lung epithelial cell line. We aimed to evaluate a therapeutic dose of PB alone or in combination with vitamin D3 for induction of LL-37 expression in immune cells and enhancement of antimycobacterial activity in monocyte-derived macrophages (MDM).

Methods

Healthy volunteers were enrolled in an 8-days open trial with three doses of PB [250 mg (Group-I), 500 mg (Group-II) or 1000 mg (Group-III)] twice daily (b.d.) together with vitamin D3 {5000 IU once daily (o.d.)}, PB (500 mg b.d.) (Group-IV) or vitamin D3 (5000 IU o.d.) (Group-V), given orally for 4 days. Blood was collected on day-0, day-4 and day-8; plasma was separated, peripheral blood mononuclear cells (PBMC), non-adherent lymphocytes (NAL) and MDM were cultured. LL-37 transcript in cells and peptide concentrations in supernatant were determined by qPCR and ELISA, respectively. In plasma, 25-hydorxyvitamin D3 levels were determined by ELISA. MDM-mediated killing of Mycobacterium tuberculosis (Mtb) (H37Rv) was performed by conventional culture method.

Results

MDM from Group-II had increased concentration of LL-37 peptide and transcript at day-4, while Group-I showed increased transcript at day-4 and day-8 compared to day-0 (p < 0.05). Both Group-I and -II exhibited higher levels of transcript on day-4 compared to Group-III and Group-V (p < 0.035). Increased induction of peptide was observed in lymphocytes from Group-II on day-4 compared to Group-I and Group-IV (p < 0.05), while Group-IV showed increased levels on day-8 compared to Group-I and Group-III (p < 0.04). Intracellular killing of Mtb on day-4 was significantly increased compared to day-0 in Group-I, -II and -V (p < 0.05).

Conclusion

The results demonstrate that 500 mg b.d. PB with 5000 IU o.d. vitamin D3 is the optimal dose for the induction of LL-37 in macrophages and lymphocytes and intracellular killing of Mtb by macrophages. Hence, this dose has potential application in the treatment of TB and is now being used in a clinical trial of adults with active pulmonary TB (NCT01580007).
Assessing the validity of a self-administered food-frequency questionnaire (FFQ) in the adult population of Newfoundland and Labrador, Canada
Authors: Liu Lin , Wang Peizhong Peter , Roebothan Barbara , Ryan Ann , Tucker Christina Sandra , Colbourne Jennifer , Baker Natasha , Cotterchio Michelle , Yi Yanqing , Sun Guang
Published: April 2013

Background

The Food- Frequency Questionnaire (FFQ) is a dietary assessment tool frequently used in large-scale nutritional epidemiology studies. The goal of the present study is to validate a self-administered version of the Hawaii FFQ modified for use in the general adult population of Newfoundland and Labrador (NL).

Methods

Over a one year period, 195 randomly selected adults completed four 24-hour dietary recalls (24-HDRs) by telephone and one subsequent self-administered FFQ. Estimates of energy and nutrients derived from the 24-HDRs and FFQs were compared (protein, carbohydrate, fibre, fat, vitamin A, carotene, vitamin D, and calcium). Data were analyzed using the Pearson’s correlation coefficients, cross-classification method, and Bland–Altman plots.

Results

The mean nutrient intake values of the 24-HDRs were lower than those of the FFQs, except for protein in men. Sex and energy-adjusted de-attenuated Pearson correlation coefficients for each nutrient varied from 0.13 to 0.61. Except for protein in men, all correlations were statistically significant with p < 0.05. Cross-classification analysis revealed that on average, 74% women and 78% men were classified in the same or adjacent quartile of nutrient intake when comparing data from the FFQ and 24-HDRs. Bland–Altman plots showed no serious systematic bias between the administration of the two instruments over the range of mean intakes.

Conclusion

This 169-item FFQ developed specifically for the adult NL population had moderate relative validity and therefore can be used in studies to assess food consumption in the general adult population of NL. This tool can be used to classify individual energy and nutrient intakes into quartiles, which is useful in examining relationships between diet and chronic disease.
The infectious synapse formed between mature dendritic cells and CD4+T cells is independent of the presence of the HIV-1 envelope glycoprotein
Authors: Rodriguez-Plata Maria T , Puigdomènech Isabel , Izquierdo-Useros Nuria , Puertas Maria C , Carrillo Jorge , Erkizia Itziar , Clotet Bonaventura , Blanco Julià , Martinez-Picado Javier
Published: April 2013

Background

Since cell-mediated infection of human immunodeficiency virus type 1 (HIV-1) is more efficient than cell-free infection, cell-to-cell propagation plays a crucial role in the pathogenesis of HIV-1 infection. Transmission of HIV-1 is enabled by two types of cellular contacts, namely, virological synapses between productively infected cells and uninfected target cells and infectious synapses between uninfected dendritic cells (DC) harboring HIV-1 and uninfected target cells. While virological synapses are driven by expression of the viral envelope glycoprotein on the cell surface, little is known about the role of envelope glycoprotein during contact between DC and T cells. We explored the contribution of HIV-1 envelope glycoprotein, adhesion molecules, and antigen recognition in the formation of conjugates comprising mature DC (mDC) and CD4+ T cells in order to further evaluate their role in mDC-mediated HIV-1 transmission at the immunological synapse.

Results

Unlike virological synapse, HIV-1 did not modulate the formation of cell conjugates comprising mDC harboring HIV-1 and non-activated primary CD4+ T cells. Disruption of interactions between ICAM-1 and LFA-1, however, resulted in a 60% decrease in mDC-CD4+ T-cell conjugate formation and, consequently, in a significant reduction of mDC-mediated HIV-1 transmission to non-activated primary CD4+ T cells (p < 0.05). Antigen recognition or sustained MHC-TcR interaction did not enhance conjugate formation, but significantly boosted productive mDC-mediated transmission of HIV-1 (p < 0.05) by increasing T-cell activation and proliferation.

Conclusions

Formation of the infectious synapse is independent of the presence of the HIV-1 envelope glycoprotein, although it does require an interaction between ICAM-1 and LFA-1. This interaction is the main driving force behind the formation of mDC-CD4+ T-cell conjugates and enables transmission of HIV-1 to CD4+ T cells. Moreover, antigen recognition boosts HIV-1 replication without affecting the frequency of cellular conjugates. Our results suggest a determinant role for immune activation driven by mDC-CD4+ T-cell contacts in viral dissemination and that this activation likely contributes to the pathogenesis of HIV-1 infection.
Unrooted unordered homeomorphic subtree alignment of RNA trees
Authors: Milo Nimrod , Zakov Shay , Katzenelson Erez , Bachmat Eitan , Dinitz Yefim , Ziv-Ukelson Michal
Published: April 2013

We generalize some current approaches for RNA tree alignment, which are traditionally confined to ordered rooted mappings, to also consider unordered unrooted mappings. We define the Homeomorphic Subtree Alignment problem (HSA), and present a new algorithm which applies to several modes, combining global or local, ordered or unordered, and rooted or unrooted tree alignments. Our algorithm generalizes previous algorithms that either solved the problem in an asymmetric manner, or were restricted to the rooted and/or ordered cases. Focusing here on the most general unrooted unordered case, we show that for input trees T and S, our algorithm has an O(n

T

n

S
 + min(d

T
,d

S
)L

T

L

S
) time complexity, where n

T
,L

T
 and d

T
are the number of nodes, the number of leaves, and the maximum node degree in T, respectively (satisfying d

T
 ≤ L

T
 ≤ n

T
), and similarly for n

S
,L

S
 and d

S
 with respect to the tree S. This improves the time complexity of previous algorithms for less general variants of the problem.

In order to obtain this time bound for HSA, we developed new algorithms for a generalized variant of the Min-Cost Bipartite Matching problem (MCM), as well as to two derivatives of this problem, entitled All-Cavity-MCM and All-Pairs-Cavity-MCM. For two input sets of size n and m, where n ≤ m, MCM and both its cavity derivatives are solved in O(n
3 + n
m) time, without the usage of priority queues (e.g. Fibonacci heaps) or other complex data structures. This gives the first cubic time algorithm for All-Pairs-Cavity-MCM, and improves the running times of MCM and All-Cavity-MCM problems in the unbalanced case where n ≪ m.

We implemented the algorithm (in all modes mentioned above) as a graphical software tool which computes and displays similarities between secondary structures of RNA given as input, and employed it to a preliminary experiment in which we ran all-against-all inter-family pairwise alignments of RNAse P and Hammerhead RNA family members, exposing new similarities which could not be detected by the traditional rooted ordered alignment approaches. The results demonstrate that our approach can be used to expose structural similarity between some RNAs with higher sensitivity than the traditional rooted ordered alignment approaches. Source code and web-interface for our tool can be found in http://www.cs.bgu.ac.il/\~negevcb/FRUUT.
Interstage mortality for functional single ventricle with heterotaxy syndrome: a retrospective study of the clinical experience of a single tertiary center
Authors: Song Jinyoung , Kang I-Seok , Huh June , Lee Ok Jeong , Kim Geena , Jun Tae Gook , Yang Ji Hyuk
Published: April 2013

Background

In spite of improved survival after palliation for single ventricle, interstage mortality for a single ventricle with heterotaxy syndrome is unknown. The purpose of this study was to quantify interstage mortality and influence mortality risk factors.

Methods

From November 1994 until February 2012, all patients that had a functional single ventricle and heterotaxy syndrome who underwent palliative operations at our center were included. Patients with hypoplastic left heart syndrome and operative mortality cases were excluded. The factors that influenced interstage mortality were determined by multivariate Cox analysis.

Results

There were 16 patients with interstage mortality (41.0%), much higher than the non-heterotaxy group (vs. 11.3%, P = 0.001, OR = 5.478). The major presumptive causes of death were infection or sepsis (37.5%) and unknown sudden death (31.3%). When we compared the survival group and the mortality group with heterotaxy syndrome, Blalock-Taussig shunt as a 1st palliation is most common for both groups but there were more for the mortality group (81.2% vs. 52.2%), and there were more with bidirectional cavo-pulmonary shunt as a 1st palliation in the survival group (10 patients vs. 2 patients). The existence of pulmonary vein stenosis at initial diagnosis was more common for the mortality group. In multivariate Cox analysis, however, the duration of hospitalization at palliation, the duration of intensive care unit stay after palliation and the existence of pulmonary vein stenosis at diagnosis were significant risk factors.

Conclusion

Interstage mortality for a functional single ventricle with heterotaxy syndrome is significantly higher than for non-heterotaxy syndrome. Therefore more attention should be given to the prevention of interstage mortality in these patients with risk factors.
Azacitidine might be beneficial in a subgroup of older AML patients compared to intensive chemotherapy: a single centre retrospective study of 227 consecutive patients
Authors: van der Helm Lieke H , Scheepers Ellen RM , Veeger Nic JGM , Daenen Simon MGJ , Mulder André B , van den Berg Eva , Vellenga Edo , Huls Gerwin
Published: April 2013

Background

Treatment options in older acute myeloid leukaemia (AML) patients include intensive chemotherapy, best supportive care (BSC), and hypomethylating agents. Currently, limited data is available on hypomethylating agents in older AML patients in unselected patient populations.

Methods

To compare the effectiveness of azacitidine with conventional therapy, we collected data of 227 consecutive AML patients (≥60 years) who were treated with azacitidine (N = 26), intensive chemotherapy (N = 90), or BSC (N = 97).

Results

Azacitidine-treated patients were older and had more comorbidities, but lower white blood cell- and bone marrow blast counts compared with intensive chemotherapy patients. Complete or partial response was achieved in 42% of azacitidine-treated patients and in 73% of intensive chemotherapy patients (P = 0.005). However, the overall survival (OS) was similar (1-year-OS 57% versus 56%,P = 0.93; 2-year-OS 35% versus 35%,P = 0.92), and remained similar after correction for risk factors in a multivariate analysis. Patients treated with BSC had an inferior OS (1-year- and 2-year-OS 16% and 2%,P < 0.001). Compared to intensive chemotherapy, azacitidine-treated patients spent less days in the hospital (median in first three months 0.5 versus 56,P < 0.001), and needed less red blood cell and platelet transfusions (median per month 2.7 versus 7,P < 0.001 and 0.3 versus 5,P < 0.001) in the first three months.

Conclusions

Azacitidine treatment is associated with a comparable OS but higher tolerability in a subgroup of older AML patients compared with intensive chemotherapy. Patients receiving BSC had a poor prognosis.
Training the next generation of clinical researchers: evaluation of a graduate podiatrist research internship in rheumatology
Authors: Naidoo Serena , Bowen Catherine , Arden Nigel , Redmond Anthony
Published: April 2013

Background

The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors.

Methods

Nine new graduates completed the internship programme (July 2006–June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes.

Results

Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent ‘Jewel in the Crown’ award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees.

Seven important themes arose from the qualitative phases: perceptions of the internship pre‐application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme.

Conclusions

The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales.
Journal of Ovarian Research reviewer acknowledgement 2012
Authors: Curiel David T , Kakar Sham S , Palomba Stefano , Tsang Benjamin K
Published: April 2013

Contributing reviewers

The editors of Journal of Ovarian Research would like to thank all of our reviewers who have contributed to the journal in volume 5 (2012).
TEOS/PDMS-OH hybrid material for the consolidation of damaged pottery
Authors: Zhao Jing , Luo Hongjie , Wang Liqin , Li Weidong , Zhou Tie , Rong Bo
Published: April 2013

The use of organic–inorganic hybrid compounds containing tetraethoxysilane (TEOS) and hydroxyl-terminated polydimethylsiloxane (PDMS-OH) is one of the most promising approaches for using alkoxysilane-based formulations to improve the effectiveness of the consolidation of traditional silicate artifacts, such as ancient stone. Based on analysis of existing damaged potteries influenced by the crystallization of NaCl salt, the hybrid we prepared in this study provided a crack-free and homogeneous gel on the premise of appropriate PDMS-OH content. The consolidants were applied to samples prepared following procedures that simulate old pottery and the effect of the protective products was evaluated by characterizing the surface morphology, the determination of the consolidant uptake, color changes, water vapour permeability and several wet-dry cycles with salt. The best formulation found for the hybrid in the present work was made up of 10% PDMS-OH with TEOS, which showed a significant increase in compressive strength, with a value of 3.50 MPa at 3 mm depth of consolidation, similar to the sample treated with Primal SF(the commercial protective agents used for comparison purposes), which had 3.20 MPa in compressive strength at 2 mm depth of consolidation. Except for small color changes and excellent water vapor permeability, there was still no significant change, and the destructive effects from NaCl crystallization for the hydrophobic surface of the sample treated with hybrid material was different to what happened for the hydrophilic case in the original. Thus, this study has revealed, for the first time, the addition of an appropriate amount of PDMS-OH to TEOS helps to improve the mechanical properties, hydrophobic behavior and salt resistance of damaged pottery effloresced by the NaCl crystals; in addition small color changes and excellent water vapor permeability should also be taken into consideration.
Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit
Authors: Alge Joseph L , Karakala Nithin , Neely Benjamin A , Janech Michael G , Velez Juan Carlos Q , Arthur John M ,   The SAKInet Investigators
Published: April 2013

Introduction

Acute kidney injury (AKI) is commonly observed in the intensive care unit (ICU), where it can be caused by a variety of factors. The objective of this study was to evaluate the prognostic value of urinary angiotensinogen, a candidate prognostic AKI biomarker identified in post-cardiac surgery patients, in this heterogeneous population.

Methods

Urinary angiotensinogen was measured by ELISA and corrected for urine creatinine in 45 patients who developed AKI in the ICU. Patients were grouped by AKI etiology, and the angiotensinogen-to-creatinine ratio (uAnCR) was compared among the groups using the Kruskal-Wallis test. The ability of uAnCR to predict the following endpoints was tested using the area under the ROC curve (AUC): the need for renal replacement therapy (RRT) or death, increased length of stay (defined as hospital discharge > 7 days or death ≤ 7 days from sample collection), and worsening AKI (defined as an increase in serum creatinine > 0.3 mg/dL after sample collection or RRT).

Results

uAnCR was significantly elevated in patients who met the composite outcome RRT or death (89.4 vs 25.4 ng/mg; P = 0.01), and it was a strong predictor of this outcome (AUC = 0.73). Patients with uAnCR values above the median for the cohort (55.21 ng/mg) had increased length of stay compared to patients with uAnCR ≤ 55.21 ng/mg (22 days vs 7 days after sample collection; P = 0.01). uAnCR was predictive of the outcome increased length of stay (AUC = 0.77). uAnCR was also a strong predictor of worsening of AKI (AUC = 0.77). The uAnCR of patients with pre-renal AKI was lower compared to patients with AKI of other causes (median uAnCR 11.3 vs 80.2 ng/mg; P = 0.02).

Conclusions

Elevated urinary angiotensinogen is associated with adverse events in AKI patients in the ICU. It could be used to identify high risk patients who would benefit from timely intervention that could improve their outcomes.
Building a Personalized Medicine Infrastructure at a Major Cancer Center
Authors: Meric-Bernstam Funda , Farhangfar Carol , Mendelsohn John , Mills Gordon B.
Published: April 2013

Our understanding of cancer biology is rapidly increasing, as is the availability and affordability of high throughput technologies for comprehensive molecular characterization of tumors and the individual's own genetic makeup. Thus, the time is right to implement personalized molecular medicine for all patients with cancer. Personalized approaches span the full cancer care spectrum from risk stratification to prevention, screening, therapy, and survivorship programs. Several molecular therapeutics have entered clinical trials creating a huge opportunity to couple genomic markers with this emerging drug tool kit. The number of patients managed in major cancer centers creates a challenge to the implementation of genomic technologies required to successfully deliver on the promise of personalized cancer care. This requires a major investment in infrastructure to facilitate rapid deployment of multiplex, cost-effective, and tissue-sparing assays relevant across multiple tumor lineages in the Clinical Laboratory Improvement Amendments (CLIA) environment. Efforts must be made to ensure that assays are accessible to patients most likely to be enrolled onto molecular-marker–driven trials and that the tests are billable and payable, which will make them accessible to a wide range of patients. As the number of patients and aberrations increase, it will become critical to provide decision support for genomic medicine. Institutional commitment is needed to optimize accessibility and quality of research biopsies and to facilitate novel personalized cancer therapy trials. This article will focus on the challenges and opportunities that accompany the building of infrastructure for personalized cancer therapy.
Lessons Learned From Lung Cancer Genomics: The Emerging Concept of Individualized Diagnostics and Treatment
Authors: Buettner Reinhard , Wolf Jürgen , Thomas Roman K.
Published: April 2013

The advent of novel therapeutics that specifically target signaling pathways activated by genetic alterations has revolutionized the way patients with lung cancer are treated. Although only few and largely ineffective chemotherapeutic regimens were available 10 years ago, a lung tumor diagnosed today requires extensive pathologic subtyping and diagnosis of genome alterations to afford more effective treatment (eg, in EGFR-mutant adenocarcinoma). This change of paradigm has several profound implications, ranging from preclinical work on the mechanism of action to a novel, more biologically oriented taxonomy and from genome diagnostics to trial design. Here, we have summarized these developments into six conceptual paradigms that illustrate the transition from empirical cancer medicine to mechanistically based individualized oncology.