bluuebunny/crossref_metadata_2025 huggingface dataset:
Myths and misconceptions about cervical cancer among Zambian women: rapid assessment by peer educators
Authors: Chirwa Susan , Mwanahamuntu Mulindi , Kapambwe Sharon , Mkumba Gracilia , Stringer Jeff , Sahasrabuddhe Vikrant , Pfaendler Krista , Parham Groesbeck
Published: July 2010

Objective. To make a rapid assessment of the common myths and misconceptions surrounding the causes of cervical cancer and lack of screening among unscreened low-income Zambian women. Methods. We initiated a door-to-door community-based initiative, led by peer educators, to inform unscreened women about the existence of a new see-and-treat cervical cancer prevention program. During home visits peer educators posed the following two questions to women: 1. What do you think causes cervical cancer? 2. Why haven’t you been screened for cervical cancer? The most frequent types of responses gathered in this exercise were analyzed thematically. Results. Peer educators contacted over 1100 unscreened women over a period of two months. Their median age was 33 years, a large majority (58%) were not educated beyond primary school, over two-thirds (71%) did not have monthly incomes over 500,000 Zambian Kwacha (US$100) per month, and just over half (51%) were married and cohabiting with their spouses. Approximately 75% of the women engaged in discussions had heard of cervical cancer and had heard of the new cervical cancer prevention program in the local clinic. The responses of unscreened low-income Zambian women to questions posed by peer educators in urban Lusaka reflect the variety of prevalent ‘folk’ myths and misconceptions surrounding cervical cancer and its prevention methods. Conclusion. The information in our rapid assessment can serve as a basis for developing future educational and intervention campaigns for improving uptake of cervical cancer prevention services in Zambia. It also speaks to the necessity of ensuring that programs addressing women’s reproductive health take into account societal inputs at the time they are being developed and implemented. Taking a community-based participatory approach to program development and implementation will help ensure sustainability and impact. (Global Health Promotion, 2010; Supp (2): pp. 47—50)
Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis
Authors: Jo Seung-Hee , Schatz Jonathan H. , Acquaviva Jaime , Singh Harinder , Ren Ruibao
Published: June 2010

Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a very early age a more aggressive chronic myelogenous leukemia-like disease than mice deficient in IRF-8 alone, correlating with a greater expansion of granulocyte-monocyte progenitors. Although these results demonstrate, for the first time, that IRF-4 can function as tumor suppressor in myeloid cells, interestingly, all mice deficient in both IRF-4 and IRF-8 eventually develop and die of a B-lymphoblastic leukemia/lymphoma. Combined losses of IRF-4 and IRF-8 therefore can cooperate in the development of both myeloid and lymphoid tumors.
Problematic severe asthma in children, not one problem but many: a GA2LEN initiative
Authors: Hedlin G. , Bush A. , Lødrup Carlsen K. , Wennergren G. , De Benedictis F.M. , Melén E. , Paton J. , Wilson N. , Carlsen K.-H.
Published: July 2010

Although most children with asthma are easy to treat with low doses of safe medications, many remain symptomatic despite every therapeutic effort. The nomenclature regarding this group is confusing, and studies are difficult to compare due to the proliferation of terms describing poorly defined clinical entities.

In this review of severe asthma in children, the term problematic severe asthma is used to describe children with any combination of chronic symptoms, acute severe exacerbations and persistent airflow limitation despite the prescription of multiple therapies.

The approach to problematic severe asthma may vary with the age of the child, but, in general, three steps need to be taken in order to separate difficult-to-treat from severe therapy-resistant asthma. First, confirmation that the problem is really due to asthma requires a complete diagnostic re-evaluation. Secondly, the paediatrician needs to systematically exclude comorbidity, as well as personal or family psychosocial disorders. The third step is to re-evaluate medication adherence, inhaler technique and the child’s environment.

There is a clear need for a common international approach, since there is currently no uniform agreement regarding how best to approach children with problematic severe asthma. An essential first step is proper attention to basic care.
Reference values for lung function: past, present and future
Authors: Stanojevic S. , Wade A. , Stocks J.
Published: July 2010

Reliable interpretation of pulmonary function results relies on the availability of appropriate reference data to help distinguish between health and disease and to assess the severity and nature of any functional impairment.

The overwhelming number of published reference equations, with at least 15 published for spirometry alone in the past 3 yrs, complicates the selection of an appropriate reference. The use of inappropriate reference equations and misinterpretation, even when potentially appropriate equations are used, can lead to serious errors in both under and over diagnosis, with its associated burden in terms of financial and human costs.

Further misdiagnosis occurs when fixed cut-offs, such as 80% predicted forced expiratory volume in 1 s (FEV1) or 0.70 FEV1/forced vital capacity, are used; particularly in young children and elderly adults. While per cent predicted has historically been used to interpret lung function results, z-scores are more appropriate as they take into account the predicted value, as well as the between-subject variability of measurements.

We aim to highlight some of the main issues in selecting and using reference equations and discuss how recent developments may improve interpretation of pulmonary function results.
Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38
Authors: Mennella Julie A , Pepino M Yanina , Duke Fujiko F , Reed Danielle R
Published: July 2010

Background

The purpose of this study was to investigate the effect of TAS2R38 haplotypes and age on human bitter taste perception.

Results

Children (3 to 10 yrs), adolescents (11 to 19 yrs) and adults (mostly mothers, 20 to 55 yrs (N = 980) were measured for bitter taste thresholds for 6-n-propylthiouracil (PROP) and genotyped for three polymorphisms of the AS2R38 gene (A49P, V262A, I296V). Subjects were grouped by haplotype and age, as well as sex and race/ethnicity, and compared for PROP thresholds. Subjects with the same haplotype were similar in bitter threshold regardless of race/ethnicity (all ages) or sex (children and adolescents; all p-values > 0.05) but age was a modifier of the genotype-phenotype relationship. Specifically, AVI/PAV heterozygous children could perceive a bitter taste at lower PROP concentrations than could heterozygous adults, with the thresholds of heterozygous adolescents being intermediate (p < 0.001). Similar age effects were not observed for subjects with the PAV/PAV or AVI/AVI homozygous haplotypes (p > 0.05) perhaps because there is less variation in taste perception among these homozygotes.

Conclusions

These data imply that the change in PROP bitter sensitivity which occurs over the lifespan (from bitter sensitive to less so) is more common in people with a particular haplotype combination, i.e., AVI/PAV heterozygotes.
Spontaneous dural tear leading to intracranial hypotension and tonsillar herniation in Marfan syndrome: a case report
Authors: Pabaney Aqueel H , Mirza Farhan A , Syed Nadir A , Ahsan Humera
Published: June 2010

Background

We describe the case of a 38 year old male with Marfan syndrome who presented with orthostatic headaches and seizures.

Case Presentation

The patient was diagnosed with Spontaneous Intracranial Hypotension secondary to CSF leaks, objectively demonstrated by MR Myelogram with intrathecal contrast. Epidural autologus blood patch was administered at the leakage site leading to significant improvement.

Conclusion

Our literature search shows that this is the second reported case of a Marfan patient presenting with symptomatic spontaneous CSF leaks along with tonsillar herniation.
A study of HIV/AIDS related knowledge, attitude and behaviors among female sex workers in Shanghai China
Authors: Cai Yong , Shi Rong , Shen Tian , Pei Bei , Jiang Xueqin , Ye Xiuxia , Xu Gang , Li Shenghui , Huang Hong , Shang Meili
Published: June 2010

Background

China is currently facing a rapid and widespread increase in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The activities of female sex workers (FSWs) have contributed to the mounting epidemic of HIV/AIDS and other sexually transmitted diseases (STDs). Therefore, this study aimed to assess the HIV/AIDS-related knowledge, attitude and risk behaviors among FSWs operating in Shanghai China.

Methods

A cross-sectional study was conducted in five districts of Shanghai, including three suburbs and two downtown locales. We adopted a cluster randomized sampling method to obtain ten geographic sites which consisted of one or more communities/villages proximal to a location where FSWs were accessible. A total of 324 FSWs from 109 Xitou Fang, massage parlors and hair salons who explicitly provided sexual services were enrolled in the study. Each participant completed a questionnaire survey and interview aimed to collect information on the individual's knowledge, attitude, and behaviors associated with risk for HIV/AIDs.

Results

The overall correct answer rate of HIV/AIDS-related knowledge was 60.8%, and the knowledge of FSWs from downtown areas was significantly higher than those from suburban areas (P < 0.05). The percentage of FSWs who reported having experiences in commercial sexual services without the use of condoms was 33.6%. Condom slippage or breakage was reported as having occurred at least once by 51.2% of the FSWs. FSWs from suburban areas were found to more often engage in high-risk behaviors, including oral and anal sex, than those from downtown areas (P < 0.001). Many of the FSWs (65.7%) reported having non-client sexual partners (most were identified as boyfriends or husbands); however, condom usage with these partners were lower (34.3%).

Conclusions

Based on the findings from our survey, we advise that promotion of HIV/AIDS-related knowledge be targeted towards FSWs in Shanghai, especially those operating in the suburbs. HIV prevention efforts, such as urging constant condom usage with both clients and steady partners, should be sustained and reinforced among the female sex workers population.
Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study
Authors: Onifade Dami A , Bayer Angela M , Montoya Rosario , Haro Marie , Alva Jessica , Franco Jessica , Sosa Rosario , Valiente Betty , Valera Enit , Ford Carolyn M , Acosta Colleen D , Evans Carlton A
Published: June 2010

Background

There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns.

Methods

We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers.

Results

We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men.

Conclusions

There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification.
Psychological risk factors of micro- and macrovascular outcomes in primary care patients with type 2 diabetes: rationale and design of the DiaDDZoB Study
Authors: Nefs Giesje , Pouwer François , Denollet Johan , Pop Victor JM
Published: July 2010

Background

Depression is a common psychiatric complication of diabetes, but little is known about the natural course and the consequences of depressive symptoms in primary care patients with type 2 diabetes. While depression has been related to poor glycemic control and increased risk for macrovascular disease, its association with microvascular complications remains understudied. The predictive role of other psychological risk factors such as Type D (distressed) personality and the mechanisms that possibly link depression and Type D personality with poor vascular outcomes are also still unclear.

Methods/Design

This prospective cohort study will examine: (1) the course of depressive symptoms in primary care patients with type 2 diabetes; (2) whether depressive symptoms and Type D personality are associated with the development of microvascular and/or macrovascular complications and with the risk of all-cause or vascular mortality; and (3) the behavioral and physiological mechanisms that may mediate these associations. The DiaDDZoB Study is embedded within the larger DIAZOB Primary Care Diabetes study, which covers a comprehensive cohort of type 2 diabetes patients treated by over 200 primary care physicians in South-East Brabant, The Netherlands. These patients will be followed during their lifetime and are assessed annually for demographic, clinical, lifestyle and psychosocial factors. Measurements include an interviewer-administered and self-report questionnaire, regular care laboratory tests and physical examinations, and pharmacy medication records. The DiaDDZoB Study uses data that have been collected during the original baseline assessment in 2005 (M0; N = 2,460) and the 2007 (M1; N = 2,225) and 2008 (M2; N = 2,032) follow-up assessments.

Discussion

The DiaDDZoB Study is expected to contribute to the current understanding of the course of depression in primary care patients with type 2 diabetes and will also test whether depressed patients or those with Type D personality are at increased risk for (further) development of micro- and cardiovascular disease. More knowledge about the mechanisms behind this association is needed to guide new intervention studies.
Genome-scale metabolic reconstruction and in silico analysis of methylotrophic yeast Pichia pastoris for strain improvement
Authors: Chung Bevan KS , Selvarasu Suresh , Camattari Andrea , Ryu Jimyoung , Lee Hyeokweon , Ahn Jungoh , Lee Hongweon , Lee Dong-Yup
Published: July 2010

Background

Pichia pastorishas been recognized as an effective host for recombinant protein production. A number of studies have been reported for improving this expression system. However, its physiology and cellular metabolism still remained largely uncharacterized. Thus, it is highly desirable to establish a systems biotechnological framework, in which a comprehensivein silicomodel ofP. pastoriscan be employed together with high throughput experimental data analysis, for better understanding of the methylotrophic yeast's metabolism.

Results

A fully compartmentalized metabolic model ofP. pastoris(iPP668), composed of 1,361 reactions and 1,177 metabolites, was reconstructed based on its genome annotation and biochemical information. The constraints-based flux analysis was then used to predict achievable growth rate which is consistent with the cellular phenotype ofP. pastorisobserved during chemostat experiments. Subsequentin silicoanalysis further explored the effect of various carbon sources on cell growth, revealing sorbitol as a promising candidate for culturing recombinantP. pastorisstrains producing heterologous proteins. Interestingly, methanol consumption yields a high regeneration rate of reducing equivalents which is substantial for the synthesis of valuable pharmaceutical precursors. Hence, as a case study, we examined the applicability ofP. pastorissystem to whole-cell biotransformation and also identified relevant metabolic engineering targets that have been experimentally verified.

Conclusion

The genome-scale metabolic model characterizes the cellular physiology ofP. pastoris, thus allowing us to gain valuable insights into the metabolism of methylotrophic yeast and devise possible strategies for strain improvement throughin silicosimulations. This computational approach, combined with synthetic biology techniques, potentially forms a basis for rational analysis and design ofP. pastorismetabolic network to enhance humanized glycoprotein production.
Identification and characterization of retinoblastoma gene mutations disturbing apoptosis in human breast cancers
Authors: Berge Elisabet Ognedal , Knappskog Stian , Geisler Stephanie , Staalesen Vidar , Pacal Marec , Børresen-Dale Anne-Lise , Puntervoll Pål , Lillehaug Johan Richard , Lønning Per Eystein
Published: July 2010

Background

The tumor suppressor pRb plays a key role regulating cell cycle arrest, and disturbances in the RB1 gene have been reported in different cancer forms. However, the literature reports contradictory findings with respect to a pro - versus anti - apoptotic role of pRb, and the consequence of alterations in RB1 to chemotherapy sensitivity remains unclear. This study is part of a project investigating alterations in pivotal genes as predictive factors to chemotherapy sensitivity in breast cancer.

Results

Analyzing 73 locally advanced (stage III) breast cancers, we identified two somatic and one germline single nucleotide changes, each leading to amino acid substitution in the pRb protein (Leu607Ile, Arg698Trp, and Arg621Cys, respectively). This is the first study reporting point mutations affecting RB1 in breast cancer tissue. In addition, MLPA analysis revealed two large multiexon deletions (exons 13 to 27 and exons 21 to 23) with the exons 21-23 deletion occurring in the tumor also harboring the Leu607Ile mutation. Interestingly, Leu607Ile and Arg621Cys point mutations both localize to the spacer region of the pRb protein, a region previously shown to harbor somatic and germline mutations. Multiple sequence alignment across species indicates the spacer to be evolutionary conserved. All three RB1 point mutations encoded nuclear proteins with impaired ability to induce apoptosis compared to wild-type pRb in vitro. Notably, three out of four tumors harboring RB1 mutations displayed primary resistance to treatment with either 5-FU/mitomycin or doxorubicin while only 14 out of 64 tumors without mutations were resistant (p = 0.046).

Conclusions

Although rare, our findings suggest RB1 mutations to be of pathological importance potentially affecting sensitivity to mitomycin/anthracycline treatment in breast cancer.
Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2
Authors: Schachtele Scott J , Hu Shuxian , Little Morgan R , Lokensgard James R
Published: June 2010

Background

Using a murine model of herpes simplex virus (HSV)-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2)-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS) are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis.

Methods

Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia.

Results

Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice.

Conclusions

These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.
Impact of dual temperature profile in dilute acid hydrolysis of spruce for ethanol production
Authors: Bösch Peter , Wallberg Ola , Joelsson Elisabeth , Galbe Mats , Zacchi Guido
Published: July 2010

Background

The two-step dilute acid hydrolysis (DAH) of softwood is costly in energy demands and capital costs. However, it has the advantage that hydrolysis and subsequent removal of hemicellulose-derived sugars can be carried out under conditions of low severity, resulting in a reduction in the level of sugar degradation products during the more severe subsequent steps of cellulose hydrolysis. In this paper, we discuss a single-step DAH method that incorporates a temperature profile at two levels. This profile should simulate the two-step process while removing its major disadvantage, that is, the washing step between the runs, which leads to increased energy demand.

Results

The experiments were conducted in a reactor with a controlled temperature profile. The total dry matter content of the hydrolysate was up to 21.1% w/w, corresponding to a content of 15.5% w/w of water insoluble solids. The highest measured glucose yield, (18.3 g glucose per 100 g dry raw material), was obtained after DAH cycles of 3 min at 209°C and 6 min at 211°C with 1% H2SO4, which resulted in a total of 26.3 g solubilized C6 sugars per 100 g dry raw material. To estimate the remaining sugar potential, enzymatic hydrolysis (EH) of the solid fraction was also performed. EH of the solid residue increased the total level of solubilized C6 sugars to a maximum of 35.5 g per 100 g dry raw material when DAH was performed as described above (3 min at 210°C and 2 min at 211°C with 1% H2SO4).

Conclusion

The dual-temperature DAH method did not yield decisively better results than the single-temperature, one-step DAH. When we compared the results with those of earlier studies, the hydrolysis performance was better than with the one-step DAH but not as well as that of the two-step, single-temperature DAH. Additional enzymatic hydrolysis resulted in lower levels of solubilized sugars compared with other studies on one-step DAH and two-step DAH followed by enzymatic hydrolysis. A two-step steam pretreatment with EH gave rise to a considerably higher sugar yield in this study.
Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH
Authors: Neill Nicholas J , Torchia Beth S , Bejjani Bassem A , Shaffer Lisa G , Ballif Blake C
Published: June 2010

Background

Microarray-based comparative genomic hybridization (aCGH) is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo) arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC) arrays, yet this has not been systematically studied in a clinical diagnostic setting.

Results

To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater.

Conclusions

Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing.
An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo
Authors: Gracey Lia E , Chen Zhi-Ying , Maniar Jay M , Valouev Anton , Sidow Arend , Kay Mark A , Fire Andrew Z
Published: July 2010

Background

The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome in vitro, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage in vitro and in vivo have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the in vivo positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA.

Results

We describe here the in vivo consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active). This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent.

Conclusions

These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin in vivo, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.
Impact of Short-Course Preoperative Radiotherapy for Rectal Cancer on Patients' Quality of Life: Data From the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 Randomized Clinical Trial
Authors: Stephens Richard J. , Thompson Lindsay C. , Quirke Phil , Steele Robert , Grieve Robert , Couture Jean , Griffiths Gareth O. , Sebag-Montefiore David
Published: June 2010

Purpose

The Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 (MRC CR07/NCIC CTG C016) trial showed that, in patients with operable rectal cancer, short-course preoperative radiotherapy (PRE) reduced the rate of local recurrence compared with surgery followed by selective postoperative chemoradiotherapy for patients with a positive circumferential resection margin. However, the advantages of giving PRE to all patients needs to be balanced against any negative impact on patients' quality of life.

Patients and Methods

All 1,350 patients were asked to complete the Medical Outcomes Study Short-Form 36-item (MOS SF-36) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal 38-item (EORTC QLQ-CR38) questionnaires. A priori hypotheses related to the impact of treatment on sexual, bowel, and physical function and general health.

Results

Male sexual dysfunction was significantly increased following surgery (P < .001), although there was no difference between treatment arms. However, a treatment difference had emerged at 6 months (PRE patients reporting significantly greater dysfunction; P = .004), which persisted out to at least 2 years (an insufficient number of female patients completed the sexual dysfunction questions to draw firm conclusions). Both treatment groups reported similar levels of decreased physical function at 3 months, but thereafter it returned to baseline levels. There was no evidence of any major changes between treatments or time points in terms of general health or bowel function, but exploratory analysis indicated a significant (P = .006 at 2 years) increase in the level of fecal incontinence with PRE.

Conclusion

These results from a large randomized trial using validated patient-completed questionnaires show that, for males, the main adverse effect was sexual dysfunction, and the main cause of this was surgery, but that PRE also affected sexual and some aspects of bowel functioning.
Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release
Authors: Suzuki Toru , Yoshida Naoko , Suzuki Emi , Okuda Erina , Perry Anthony C. F.
Published: July 2010

In vertebrates, a rise in intracellular free Ca2+ (Ca2+i) levels during fertilization initiates second metaphase (mII) exit and the developmental programme. The Ca2+ rise has long been considered to be crucial for development, but verifying this contribution would benefit from defining its role during fertilization. Here, we delineate the role of Ca2+ release during mII exit in wild-type mouse eggs and show that it is dispensable for full-term development. Exit from mII can be induced by Zn2+-specific sequestration without Ca2+ release, eliciting Cyclin B degradation in a manner dependent upon the proteasome pathway and intact microtubules, but not accompanied by degradation of the meiotic regulator Emi2. Parthenogenotes generated by Zn2+ sequestration developed in vitro with normal expression of Ca2+-sensitive genes. Meiotic exit induced by either Ca2+ oscillations or a single Ca2+ rise in oocytes containing a signaling-deficient sperm resulted in comparable developmental rates. In the absence of Ca2+ release, full-term development occurred ∼50% less efficiently, but at readily detectable rates, with the birth of 27 offspring. These results show in intact mouse oocytes that Zn2+ is essential for mII arrest and suggest that triggering meiotic exit is the sole indispensable developmental role of Ca2+ signaling in mammalian fertilization.
The Fatigue Life of Contoured Cobalt Chrome Posterior Spinal Fusion Rods
Authors: Nguyen T-Q , Buckley J M , Ames C , Deviren V
Published: July 2010

Intraoperative contouring of posterior rods in lumbar arthrodesis constructs introduces stress concentrations that can substantially reduce fatigue life. The sensitivity of titanium (Ti) and stainless steel (SS) to intraoperative contouring has been established in the literature; however, notch sensitivity has yet to be quantified for cobalt chrome (CoCr), which is now being advocated for use in posterior arthrodesis constructs. The goal of this study is to evaluate the sensitivity of CoCr rods to intraoperative contouring for posterior lumbar screw—rod arthrodesis constructs.

In this paper lumbar bilateral vertebrectomy models are constructed based on ASTM F1717-01 with curved rods (26—30° total curvature) and poly-axial pedicle screws. Three types of constructs are assembled: first, 5.5 mm SS rods with SS screws (6.5×35 mm), second, 6.0 mm Ti rods with Ti screws (7.5×35 mm), and third, 6.0 mm CoCr rods with Ti screws (7.5×35 mm). All specimens are tested at 4 Hz in dynamic axial compression-bending with a load ratio of ten and maximum load levels of 250, 400, and 700 N until run-out at 2 000 000 cycles.

Results are presented that show that the fatigue life of CoCr constructs tend to be greater than Ti constructs at all levels. At the 400 N maximum loading, CoCr lasts an average of 350 000 cycles longer than the Ti constructs. The CoCr constructs are able to sustain the 250 N load until run-out at 2 000 000 cycles but they fail at high load levels (maximum 700 N). The CoCr constructs fail at the neck of the Ti screw at high loads whereas Ti screws fail at the notch induced by contouring. Since CoCr is compatible with magnetic resonance imaging and has high static strength characteristics, the results of this study suggest that it may be an appropriate substitute for Ti.
In vitro models for bone mechanobiology: Applications in bone regeneration and tissue engineering
Authors: Thompson M S , Epari D R , Bieler F , Duda G N
Published: July 2010

Healthy bone healing is a remarkable, mechanically sensitive, scar-free process that leads rapidly to repair tissue of high mechanical quality and functionality, and knowledge of this process is essential for driving advances in bone tissue engineering and regeneration. Gaining this knowledge requires the use of models to probe and understand the detailed mechanisms of healing, and the tight coupling of biology and mechanics make it essential that both of these aspects are controlled and analysed together, using a mechanobiological approach. This article reviews the literature on in vitro models used for this purpose, beginning with two-dimensional (2D) cell culture models used for applying controlled mechanical stimuli to relevant cells, and detailing the analysis techniques required for understanding both substrate strain and fluid flow stimuli in sufficient detail to relate them to biological response. The additional complexity of three-dimensional (3D) models, enabling more faithful representation of the healing situation, can require correspondingly more sophisticated tools for mechanical and biological analysis, but has recently uncovered exciting evidence for the mechanical sensitivity of angiogenesis, essential for successful healing. Studies using explanted tissue continue to be vital in informing these approaches, providing additional evidence for the relevance of effects in biological and mechanical environments close to those in the living organism. Mechanobiology is essential for the proper analysis of models for bone regeneration, and has an exciting integrative role to play not only in advancing knowledge in this area, but also in ensuring successful translation of new tissue engineering and regenerative therapies to the clinic.
Two countries divided by a common language: health systems in the UK and USA
Authors: Desai Monica , Rachet Bernard , Coleman Michel P , McKee Martin
Published: July 2010

Despite the historic significance of the healthcare reform bill that was passed into law by President Obama in March 2010, the debate still rages. The UK National Health Service (NHS) has featured prominently in the current American debate on healthcare reform, with critics calling attention to its perceived shortcomings. Some of these, such as the existence of ‘death panels’, can easily be dismissed, but others, such as the cancer survival deficit, cannot. This paper reviews the evidence on outcomes from cancer and other chronic non-communicable diseases, the two leading causes of death in both countries. The headline figures showing better cancer survival in the USA are exaggerated by methodological issues, but a gap remains, due in large part to better outcomes among older people. Outcomes among younger people with chronic disease are, however, much worse in the USA. Paradoxically, given the nature of the debate in the USA so far, those parts of the US health system that get the best results, such as the Veterans' Administration, or the elderly on Medicare, are those that most closely resemble the British NHS – but which are funded somewhat more generously.
Understanding What Matters to Patients – Identifying Key Patients’ Perceptions of Quality
Authors: Doyle Cathal , Reed Julie , Woodcock Tom , Bell Derek
Published: July 2010

Objectives

To demonstrate a statistical method to enable the identification of key drivers of quality from a patient perspective that can be used by service providers to help drive improvement.

Design

Crosstabulation, Chi-square analysis and Cramer's V calculation using SPSS software of NHS Inpatient Surveys 2006 and 2007.

Setting

The NHS Inpatient Survey is a standardized survey designed by the Picker Institute conducted on a sample of patients across all acute care hospital trusts in England.

Participants

The surveys (available from the UK Data Archive) provide anonymized patient data for over 77,000 patients in 2006 and 72,000 patients in 2007.

Main outcome measures

Cramer's V score testing associations between patient ratings on multiple components of care and ratings on the overall quality of care.

Results

Of the 58 questions analysed, some questions correlate more strongly with overall satisfaction of care than others and there is strong agreement of results over the two years. Of the top 20 rated components, communication (both between professionals and between professionals and patients) and trust engendered by that communication is a recurring theme.

Conclusions

Hospital trusts are required to develop quality indicators and collate detailed feedback from patients in addition to the annual inpatient survey to measure these. To make best use of resources, additional data collection should focus on those aspects of care of most importance to patients locally. This analysis demonstrates a statistical technique that can help to identify such priority areas by showing those aspects of care most strongly associated with the overall rating of care. The analysis uses national level data to demonstrate how this can be achieved. This shows the importance to patients of being treated with dignity and respect, and good communication between staff and between staff and patients.
The codon specificity of eubacterial release factors is determined by the sequence and size of the recognition loop
Authors: Young David J. , Edgar Christina D. , Poole Elizabeth S. , Tate Warren P.
Published: June 2010

The two codon-specific eubacterial release factors (RF1: UAA/UAG and RF2: UAA/UGA) have specific tripeptide motifs (PXT/SPF) within an exposed recognition loop shown in recent structures to interact with stop codons during protein synthesis termination. The motifs have been inferred to be critical for codon specificity, but this study shows that they are insufficient to determine specificity alone. Swapping the motifs or the entire loop between factors resulted in a loss of codon recognition rather than a switch of codon specificity. From a study of chimeric eubacterial RF1/RF2 recognition loops and an atypical shorter variant in Caenorhabditis elegans mitochondrial RF1 that lacks the classical tripeptide motif PXT, key determinants throughout the whole loop have been defined. It reveals that more than one configuration of the recognition loop based on specific sequence and size can achieve the same desired codon specificity. This study has provided unexpected insight into why a combination of the two factors is necessary in eubacteria to exclude recognition of UGG as stop.
Sharing Supermodular Costs
Authors: Schulz Andreas S. , Uhan Nelson A.
Published: July 2010

We study cooperative games with supermodular costs. We show that supermodular costs arise in a variety of situations; in particular, we show that the problem of minimizing a linear function over a supermodular polyhedron—a problem that often arises in combinatorial optimization—has supermodular optimal costs. In addition, we examine the computational complexity of the least core and least core value of supermodular cost cooperative games. We show that the problem of computing the least core value of these games is strongly NP-hard and, in fact, is inapproximable within a factor strictly less than 17/16 unless P = NP. For a particular class of supermodular cost cooperative games that arises from a scheduling problem, we show that the Shapley value—which, in this case, is computable in polynomial time—is in the least core, while computing the least core value is NP-hard.
Simulation of a localized surface-plasmon-resonance-based fiber optic temperature sensor
Authors: Srivastava Sachin K. , Gupta Banshi D.
Published: June 2010

A fiber optic temperature sensor based on localized surface plasmon resonance of spherical gold nanoparticles embedded in a dielectric layer around the unclad core of a small portion of the fiber has been analyzed. Simulations have been carried out for a number of dielectric materials that show considerable changes in their refractive indices due to a change in the temperature in addition to having refractive indices higher than that of the fiber core. The analysis is based on the spectral interrogation method. The surface plasmons in metal nanoparticles have been excited by the light refracted through the core and the dielectric interface. The sensitivity of the sensor has been determined for each dielectric material used, and it is found to be the maximum for CdGeP2 as a sensing medium. The temperature sensing range of the present sensor is also wide because the melting points of the metal and the fiber core, as well as the sensing medium, are large. The proposed fiber optic temperature sensor is compact, light weight, and highly sensitive with a wide temperature sensing range.
How Addictive Can Cigarettes Be? Two Case Reports
Authors: West Oliver , McRobbie Hayden , Hajek Peter
Published: July 2010

The addiction literature contains numerous case reports of individuals dependent on a range of chemical substances, but strong dependence on cigarettes has not been similarly documented. This report attempts to fill this gap by describing two exceptionally dependent smokers. Both suffer with a smoking-related disease and have a very strong motivation to quit. Despite receiving intensive behavioural and pharmacological treatments to help them stop smoking, they have been unable to maintain even a short period of abstinence. The two cases provide reference examples for the assertion that while not all smokers are hopelessly hooked, some are. Such illustrative cases may stimulate research into the area of individual differences in cigarette dependence.
Asian Smokefree Communities: Evaluation of a Community-Focused Smoking Cessation and Smokefree Environments Intervention In New Zealand
Authors: Wong Grace , Whittaker Robyn , Chen Janet , Cowling Lis , Mil Janice van , Lim Sue
Published: July 2010

Language, culture and not knowing how to access services are barriers to the use of health services for Asian migrants. Asian Smokefree Communities (ASC) pilot-tested a novel Asian-specific service model to address these issues for Asian smokers. Korean- and Chinese-speaking coordinators delivered home-, workplace- or clinic-based interventions to support smokers with cessation and create smoke-free environments with families. A prior planned evaluation investigated the acceptability of the service, quit rates and exposure to second-hand smoke. The methods included analysis of ASC service records, a client satisfaction survey and key informant interviews. Clients were satisfied with factors associated with culture, such as being comfortable when talking to coordinators (88.9%) and family involvement in treatment (79.4%). Appointment attendance was high (97%). The self-reported quit rate for the 93 cessation clients was 72% at 1 month, 53.8 % at 3 months and 40.9 % at 6 months. All homes (100%) were smoke-free after the intervention, an increase of 18% from preintervention levels. The ASC model was acceptable to Asian clients. It helped them stop smoking and increased household protection from second-hand smoke. The model could make an effective contribution to smoke-free services for Asian populations in western countries.
Explorations of Self-Efficacy: Personal Narratives as Qualitative Data in the Analysis of Smoking Cessation Efforts
Authors: Rollins Erin , Terrion Jenepher Lennox
Published: July 2010

Research has found that an individual's perceived self-efficacy, supported by goals and the acceptance of potential obstacles, has the ability to assist in behaviour modification. By examining the narratives of cardiovascular patients undergoing smoking cessation counselling, this study highlights factors that individuals communicate in their narratives regarding changes to self-efficacy throughout the process of smoking cessation. Narrative analysis is used to establish those factors that cardiovascular patients assert to be the motivating or impeding factors in their smoking cessation efforts, particularly in relation to their initial readiness to quit smoking. The study's findings illustrate the social, physical and psychological barriers and motivating factors that exist for cardiovascular patients in the process of quitting smoking. The current study supplements past research illustrating that in-hospital programs are among the most influential smoking intervention strategies because they can be tailored to each patient's specific health problems and personal and social circumstances. The study concludes that the relationship formed between patients and intervention specialists can assist in raising an individual's self-efficacy to end an addictive behaviour.
A Qualitative Perspective on Multiple Health Behaviour Change: Views of Smoking Cessation Advisors Who Promote Physical Activity
Authors: Everson-Hock Emma S. , Taylor Adrian H. , Ussher Michael , Faulkner Guy
Published: July 2010

There are mixed views on whether smoking cessation advisors should focus only on quitting smoking or also promote simultaneous health behaviour changes (e.g., diet, physical activity), but no studies have qualitatively examined the views and vicarious experiences of such health professionals. Semi-structured interviews were conducted with 11 trained smoking cessation advisors who promote physical activity to their clients. The data were categorised into themes using thematic analysis supported by qualitative data analysis software. We report themes that were related to why advisors promote multiple health behaviour change and issues in timing. Physical activity could be promoted as a cessation aid and also as part of a holistic lifestyle change consistent with a nonsmoker identity, thereby increasing feelings of control and addressing fear of weight gain. Multiple changes were promoted pre-quit, simultaneously and post-quit, and advisors asserted that it is important to focus on the needs and capabilities of individual clients when deciding how to time multiple changes. Also, suggesting that PA was a useful and easily performed cessation aid rather than a new behaviour (i.e., structured exercise that may seem irrelevant) may help some clients to avoid a sense of overload.