bluuebunny/crossref_metadata_2025 huggingface dataset:
Study Protocol: The Behaviour and Pain in Dementia Study (BePAID)
Authors: Scott Sharon , Jones Louise , Blanchard Martin R , Sampson Elizabeth L
Published: October 2011

Background

People with dementia admitted to the acute hospital often receive poor quality care particularly with regards to management of behavioural and psychiatric symptoms of dementia (BPSD) and of pain. There have been no UK studies on the prevalence and type of pain or BPSD in people with dementia in this setting, or on how these may impact on patients, carers, staff and costs of care.

Methods/Design

We shall recruit older people with dementia who have unplanned acute medical admissions and measure the prevalence of BPSD using the Behave-AD (Behaviour in Alzheimer's Disease) and the CMAI (Cohen Mansfield Agitation Inventory). Pain prevalence and severity will be assessed by the PAINAD (Pain Assessment in Advanced Dementia) and the FACES pain scale. We will then analyse how these impact on a variety of outcomes and test the hypothesis that poor management of pain is associated with worsening of BPSD.

Discussion

By demonstrating the costs of BPSD to individuals with dementia and the health service this study will provide important evidence to drive improvements in care. We can then develop effective training for acute hospital staff and alternative treatment strategies for BPSD in this setting.
Amsterdam wrist rules: A clinical decision aid
Authors: Bentohami Abdelali , Walenkamp Monique MJ , Slaar Annelie , Beerekamp M Suzan H , de Groot Joris AH , Verhoog Eva M , Jager L Cara , Maas Mario , Bijlsma Taco S , van Dijkman Bart A , Schep Niels WL , Goslings J C
Published: October 2011

Background

Acute trauma of the wrist is one of the most frequent reasons for visiting the Emergency Department. These patients are routinely referred for radiological examination. Most X-rays however, do not reveal any fractures. A clinical decision rule determining the need for X-rays in patients with acute wrist trauma may help to percolate and select patients with fractures.

Methods/Design

This study will be a multi-center observational diagnostic study in which the data will be collected cross-sectionally. The study population will consist of all consecutive adult patients (≥18 years) presenting with acute wrist trauma at the Emergency Department in the participating hospitals.

This research comprises two components: one study will be conducted to determine which clinical parameters are predictive for the presence of a distal radius fracture in adult patients presenting to the Emergency Department following acute wrist trauma. These clinical parameters are defined by trauma-mechanism, physical examination, and functional testing. This data will be collected in two of the three participating hospitals and will be assessed by using logistic regression modelling to estimate the regression coefficients after which a reduced model will be created by means of a log likelihood ratio test. The accuracy of the model will be estimated by a goodness of fit test and an ROC curve. The final model will be validated internally through bootstrapping and by shrinking it, an adjusted model will be generated.

In the second component of this study, the developed prediction model will be validated in a new dataset consisting of a population of patients from the third hospital. If necessary, the model will be calibrated using the data from the validation study.

Discussion

Wrist trauma is frequently encountered at the Emergency Department. However, to this date, no decision rule regarding this type of trauma has been created. Ideally, radiographs are obtained of all patients entering one of the participating hospitals with trauma to the wrist. However, this is ethically and logistically not feasible and one could argue that patients, for whom no radiography is required according to their physician, are not suspected of having a distal radius fracture and thus are not part of the domain.

Trial registration

This study is registered at the Netherlands Trial Register (NTR 2544) and was granted permission by the Medical Ethical Committee of the Academic Medical Center Amsterdam on 06-01-2011.
Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch -1 receptor
Authors: Raghu Hari , Gondi Christopher S , Dinh Dzung H , Gujrati Meena , Rao Jasti S
Published: October 2011

Background

uPA/uPAR is a multifunctional system that is over expressed in many cancers and plays a critical role in glioblastoma (GBM) invasion. Previous studies from our lab have also shown that uPA/uPAR down regulation inhibits cancer cell invasion in SNB 19 GBM cells.

Methods

As Notch 1 is known to be over expressed and promotes invasion in glioblastoma, we therefore tested our hypothesis of whether down regulation of uPA/uPAR, singly or in tandem, attenuates GBM invasion via Notch 1 receptor. Targeted down regulation of uPA/uPAR, either singly or simultaneously, inhibited the anchorage independent growth of U251MG and GBM xenograft cell lines 4910 and 5310 as assessed by soft agar colony formation assay. Expression of all four Notch receptors was confirmed in GBM tissue array analysis by immunohistochemistry.

Results

Down regulation of uPA/uPAR, either singly or simultaneously, in U251 MG and tumor xenografts inhibited the cleavage of the Notch receptor between the Gly 1743 and Val 1744 positions, thereby suggesting inhibition of activated cytosolic fragment-related Notch gene transcription. Morphological analysis confirmed inhibition of NICD when U251 MG cells were treated with puPA, puPAR or pU2. uPA/uPAR down regulation inhibited Notch 1 mRNA in all three examined cell lines. uPA/uPAR shRNA down regulated nuclear activation of NF-κB subunits and phosphorylation of AKT/mTOR pathway in U251 MG and GBM xenografts. puPA down regulated NICD and HES induced phosphorylation of AKT/ERK and NF-κB. Down regulation of Notch 1 using siRNA inhibited uPA activity as shown by fibrinogen zymography. It also decreased uPA expression levels as shown by western blotting. Exogenous addition of uPA activated Notch 1 in uPAR antisense U251 MG cells and also in uPAR antisense cells transfected with siRNA against Delta and Jagged. The Notch 1 receptor co-localized with LAMP-1, a marker for lysosomes in uPA, uPAR and U2, down regulated U251 MG cells which probably indicates inhibition of Notch 1 receptor trafficking in GBM cells. Notch 1 expression was significantly inhibited in puPA- and pU2-treated pre-established intracranial tumors in mice.

Conclusions

Overall our results show that down regulation of uPA/uPAR, either singly or simultaneously, could be an effective approach to attenuate Notch 1 receptor cleavage, signaling and endosomal trafficking in U251MG cells and xenografts, and ultimately inhibiting GBM invasion.
An effective hybrid of hill climbing and genetic algorithm for 2D triangular protein structure prediction
Authors: Su Shih-Chieh , Lin Cheng-Jian , Ting Chuan-Kang
Published: October 2011

Background

Proteins play fundamental and crucial roles in nearly all biological processes, such as, enzymatic catalysis, signaling transduction, DNA and RNA synthesis, and embryonic development. It has been a long-standing goal in molecular biology to predict the tertiary structure of a protein from its primary amino acid sequence. From visual comparison, it was found that a 2D triangular lattice model can give a better structure modeling and prediction for proteins with short primary amino acid sequences.

Methods

This paper proposes a hybrid of hill-climbing and genetic algorithm (HHGA) based on elite-based reproduction strategy for protein structure prediction on the 2D triangular lattice.

Results

The simulation results show that the proposed HHGA can successfully deal with the protein structure prediction problems. Specifically, HHGA significantly outperforms conventional genetic algorithms and is comparable to the state-of-the-art method in terms of free energy.

Conclusions

Thanks to the enhancement of local search on the global search, the proposed HHGA achieves promising results on the 2D triangular protein structure prediction problem. The satisfactory simulation results demonstrate the effectiveness of the proposed HHGA and the utility of the 2D triangular lattice model for protein structure prediction.
Cervical adenoid basal carcinoma associated with invasive squamous cell carcinoma: A report of rare co-existence and review of literature
Authors: Viriyapak Boonlert , Park Sung Taek , Lee Ah Won , Park Jong Sup , Lee Chung Won , Song Min Jong , Hur Soo Young
Published: October 2011

Cervical adenoid basal carcinoma (ABC) rarely can harbor associated malignancies like adenoid cystic carcinoma or squamous cell carcinoma (SCC), which express markedly different prognosis from a pure ABC, making an appropriate biopsy essential to provide a clear diagnosis and therapeutic plan. We report a 64-year-old asymptomatic lady with an abnormal cervical cytology, who underwent a conization to reveal an ABC with overlying microinvasive SCC. Doubtful resection margins led us to perform radical hysterectomy with lymph node dissection. Subsequent pathological examination showed a true invasive SCC co-existing with ABC, with invasion of the parametrium. Unlike the indolent course of many pure ABC patients, the prognosis of 11 previously reported co-existing invasive SCC with ABC patients appears to depend on the SCC component. Our case reiterates the importance of adequate biopsy with careful interpretation to cover the possibility of a co-existent malignancy. Besides, it presents an argument in favor of radical surgery for the primary treatment of suspicious associated malignancy, and supports adjuvant treatment according to the unfavorable extent of the co-existent invasive carcinoma.
Effects of nutritional cues on the duration of the winter anovulatory phase and on associated hormone levels in adult female Welsh pony horses (Equus caballus)
Authors: Salazar-Ortiz Juan , Camous Sylvaine , Briant Christine , Lardic Lionel , Chesneau Didier , Guillaume Daniel
Published: October 2011

Background

Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm.

Methods

Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim of mimicking the natural seasonal variation of pasture availability, but a few months in advance of this natural rhythm.

Results

Winter ovarian inactivity always occurred and was long in the restricted group. In contrast, in the 'well-fed' group, 40% of mares showed this inactivity, which was shorter than in the other groups. Re-feeding the 'variable' group in autumn and winter did not advance the first ovulation in spring, compared with the 'restricted' group. Measurements of glucose and insulin concentrations in mares from the 'restricted' group during two 24 h periods of blood sampling, revealed no post-prandial peaks. For GH (Growth hormone), IGF-1 and leptin levels, large differences were found between the 'well-fed' group and the other groups. The glucose, insulin, GH and leptin levels but not melatonin level are highly correlated with the duration of ovulatory activity.

Conclusions

The annual rhythm driven by melatonin secretion is only responsible for the timing of the breeding season. The occurrence and length of winter ovarian inactivity is defined by metabolic hormones.
Synthesis of NaYF4:Yb3+, Er3+ upconversion nanoparticles in normal microemulsions
Authors: Shan Shu-Nan , Wang Xiu-Ying , Jia Neng-Qin
Published: October 2011

An interface-controlled reaction in normal microemulsions (water/ethanol/sodium oleate/oleic acid/n-hexane) was designed to prepare NaYF4:Yb3+, Er3+ upconversion nanoparticles. The phase diagram of the system was first studied to obtain the appropriate oil-in-water microemulsions. Transmission electron microscopy and X-ray powder diffractometer measurements revealed that the as-prepared nanoparticles were spherical, monodisperse with a uniform size of 20 nm, and of cubic phase with good crystallinity. Furthermore, these nanoparticles have good dispersibility in nonpolar organic solvents and exhibit visible upconversion luminescence of orange color under continuous excitation at 980 nm. Then, a thermal treatment for the products was found to enhance the luminescence intensity. In addition, because of its inherent merit in high yielding and being economical, this synthetic method could be utilized for preparation of the UCNPs on a large scale.
Improved characteristics of near-band-edge and deep-level emissions from ZnO nanorod arrays by atomic-layer-deposited Al2O3 and ZnO shell layers
Authors: Sun Wen-Cheng , Yeh Yu-Cheng , Ko Chung-Ting , He Jr-Hau , Chen Miin-Jang
Published: October 2011

We report on the characteristics of near-band-edge (NBE) emission and deep-level band from ZnO/Al2O3 and ZnO/ZnO core-shell nanorod arrays (NRAs). Vertically aligned ZnO NRAs were synthesized by an aqueous chemical method, and the Al2O3 and ZnO shell layers were prepared by the highly conformal atomic layer deposition technique. Photoluminescence measurements revealed that the deep-level band was suppressed and the NBE emission was significantly enhanced after the deposition of Al2O3 and ZnO shells, which are attributed to the decrease in oxygen interstitials at the surface and the reduction in surface band bending of ZnO core, respectively. The shift of deep-level emissions from the ZnO/ZnO core-shell NRAs was observed for the first time. Owing to the presence of the ZnO shell layer, the yellow band associated with the oxygen interstitials inside the ZnO core would be prevailed over by the green luminescence, which originates from the recombination of the electrons in the conduction band with the holes trapped by the oxygen vacancies in the ZnO shell.

PACS 68.65.Ac; 71.35.-y; 78.45.+h; 78.55.-m; 78.55.Et; 78.67.Hc; 81.16.Be; 85.60.Jb.
Liposomal doxorubicin improves radiotherapy response in hypoxic prostate cancer xenografts
Authors: Hagtvet Eirik , Røe Kathrine , Olsen Dag R
Published: October 2011

Background

Tumor vasculature frequently fails to supply sufficient levels of oxygen to tumor tissue resulting in radioresistant hypoxic tumors. To improve therapeutic outcome radiotherapy (RT) may be combined with cytotoxic agents.

Methods

In this study we have investigated the combination of RT with the cytotoxic agent doxorubicin (DXR) encapsulated in pegylated liposomes (PL-DXR). The PL-DXR formulation Caelyx® was administered to male mice bearing human, androgen-sensitive CWR22 prostate carcinoma xenografts in a dose of 3.5 mg DXR/kg, in combination with RT (2 Gy/day × 5 days) performed under normoxic and hypoxic conditions. Hypoxic RT was achieved by experimentally inducing tumor hypoxia by clamping the tumor-bearing leg five minutes prior to and during RT. Treatment response evaluation consisted of tumor volume measurements and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with subsequent pharmacokinetic analysis using the Brix model. Imaging was performed pre-treatment (baseline) and 8 days later. Further, hypoxic fractions were determined by pimonidazole immunohistochemistry of excised tumor tissue.

Results

As expected, the therapeutic effect of RT was significantly less effective under hypoxic than normoxic conditions. However, concomitant administration of PL-DXR significantly improved the therapeutic outcome following RT in hypoxic tumors. Further, the pharmacokinetic DCE MRI parameters and hypoxic fractions suggest PL-DXR to induce growth-inhibitory effects without interfering with tumor vascular functions.

Conclusions

We found that DXR encapsulated in liposomes improved the therapeutic effect of RT under hypoxic conditions without affecting vascular functions. Thus, we propose that for cytotoxic agents affecting tumor vascular functions liposomes may be a promising drug delivery technology for use in chemoradiotherapy.
Clinical application of CT-guided 125I seed interstitial implantation for local recurrent rectal carcinoma
Authors: Wang Zhongmin , Lu Jian , Liu Lin , Liu Tao , Chen Kemin , Liu Fenju , Huang Gang
Published: October 2011

Purpose

The present study aimed to explore the safety profile and clinical efficacy of CT-guided radioactive seed implantation in treating local recurrent rectal carcinoma.

Materials and methods

CT-guided 125I seed implantation was carried out in 20 patients with locally recurrent rectal carcinoma. 14 of the 20 patient had prior adjuvant external-beam radiation therapy (EBRT). The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 120 Gy (range, 100-160 Gy).

Results

Of the 20 patients, 12 were male, 8 were female, and ages ranged from 38 to 78, with a median age of 62. Duration of follow-up was 3-34 months. The response rate of pain relief was 85% (17/20). Repeat CT scan 2 months following the procedure revealed complete response (CR) of the tumor in 2 patients, partial response (PR) in 13 patients, stable disease (SD) in 3 patients, and progressive disease (PD) in 2 patients. 75% of patients had either CR or PR. Median survival time was 18.8 months (95% CI: 3.5-22.4 months). 1 and 2 year survival rates were 75% and 25%, respectively. 4 patients died of recurrent tumor; 4 patients died of distant metastases; 9 patients died of recurrent tumor and distant metastases. 3 patients survived after 2 year follow up. Two patients were found to have mild hematochezia, which was reversible with symptomatic management.

Conclusion

CT-guided 125I seed implantation appeared to be a safe, useful and less complicated interventional treatment option for local recurrent rectal carcinoma.
Prognostic factors of atrial fibrillation following elective coronary artery bypass grafting: the impact of quantified intraoperative myocardial ischemia
Authors: Koletsis Efstratios N , Prokakis Christos , Crockett James R , Dedeilias Panagiotis , Panagiotou Matthew , Panagopoulos Nikolaos , Anastasiou Nikolaos , Dougenis Dimitrios , Apostolakis Efstratios
Published: October 2011

Background

Atrial fibrillation (AF) occurs in 28-33% of the patients undergoing coronary artery revascularization (CABG). This study focuses on both pre- and peri-operative factors that may affect the occurrence of AF. The aim is to identify those patients at higher risk to develop AF after CABG.

Patients and methods

Two patient cohorts undergoing CABG were retrospectively studied. The first group (group A) consisted of 157 patients presenting AF after elective CABG. The second group (group B) consisted of 191 patients without AF postoperatively.

Results

Preoperative factors presenting significant correlation with the incidence of post-operative AF included: 1) age > 65 years (p = 0.029), 2) history of AF (p = 0.022), 3) chronic obstructive pulmonary disease (p = 0.008), 4) left ventricular dysfunction with ejection fraction < 40% (p = 0.015) and 5) proximal lesion of the right coronary artery (p = 0.023). The intraoperative factors that appeared to have significant correlation with the occurrence of postoperative AF were: 1) CPB-time > 120 minutes (p = 0.011), 2) myocardial ischemia index < 0.27 ml.m2/Kg.min (p = 0.011), 3) total positive fluid-balance during ICU-stay (p < 0.001), 4) FiO2/PO2 > 0, 4 after extubation and during the ICU-stay (p = 0.021), 5) inotropic support with doses 15-30 μg/Kg/min (p = 0.016), 6) long ICU-stay recovery for any reason (p < 0.001) and perioperative myocardial infarction (p < 0.001).

Conclusions

Our results suggest that the incidence of post-CABG atrial fibrillation can be predicted by specific preoperative and intraoperative measures. The intraoperative myocardial ischemia can be sufficiently quantified by the myocardial ischemia index. For those patients at risk we would suggest an early postoperative precautionary anti-arrhythmic treatment.
Solitary pulmonary nodule of benign metastasizing leiomyoma associated with primary lung cancer: a case report
Authors: Naito Masahiro , Kobayashi Tetsu , Yoshida Masamichi , Fujiwara Kentaro , Onishi Masahiro , Fujiwara Atsushi , Takagi Takehiro , Kobayashi Hiroyasu , Gabazza Esteban C , Takei Yoshiyuki , Taguchi Osamu
Published: October 2011

Introduction

Benign metastasizing leiomyoma in the lung is a very rare disease characterized by the growth of uterine leiomyoma tissue. In most cases there is a previous history of hysterectomy for uterine leiomyoma.

Case presentation

A 50-year-old Asian woman underwent a total abdominal hysterectomy for uterine leiomyoma at the age of 37 years old. She was referred to our hospital because of sudden anterior chest pain. A chest computed tomography scan revealed a ground-glass opacity in her left S10 lung segment and a solitary small nodule in her left bronchial segment, S4. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to enable us to determine a further therapeutic strategy. The ground-glass opacity in her left S10 was a primary lung adenocarcinoma, while the small nodule in her left S4 was diagnosed as a benign metastasizing leiomyoma. No additional therapy was done and our patient was followed up with chest computed tomography. Up to date, repetitive evaluation by chest computed tomography has shown no sign of benign metastasizing leiomyoma or lung cancer recurrence.

Conclusion

This is a very rare case of benign metastasizing leiomyoma of the lung associated with primary lung cancer. This comorbid association should be considered in the differential diagnosis when a solitary lung nodule is detected in a patient with a history of uterine leiomyoma.
De novo 7p partial trisomy characterized by subtelomeric FISH and whole-genome array in a girl with mental retardation
Authors: S Aswini , Padmalatha Venkata O , G Saranya , T Durgadatta , T Raseswari , Kulashekaran Kanakavalli M , J Meena , N Chandra , S Lalji , Kandukuri Lakshmi R
Published: October 2011

Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.
Performance measures in aeromagnetic compensation
Authors: Noriega Gerardo
Published: October 2011

Aeromagnetic compensation is essential for the generation of highly accurate data in airborne geophysical surveys. Its objective is the removal of magnetic interference (or noise) in the signals, measured by magnetometer sensors, which is caused by the maneuvering of an aircraft flying within the Earth's magnetic field. These interference effects associated with the airframe of the aircraft, can be divided into three groups (Leliak, 1961): (a) permanent magnetism, from ferromagnetic parts in the aircraft; (b) induced magnetism, created by the Earth's magnetic field in soft iron or paramagnetic parts; and (c) eddy-current magnetic fields, created from electric currents produced on electrically conducting paths of the airframe, directly proportional to the rate of change of the magnetic flux.
The synchronized electromagnetic impulsive source
Authors: Pramik Bill , Bell Lee
Published: October 2011

Land seismic acquisition can be challenging, even in the best conditions and terrains. When the terrain changes from rural fields to industrial, urban, or environmentally sensitive areas, the challenges become more significant. A major factor that influences the difficulty and cost of seismic acquisition is the seismic source.
Phosphatidylinositol 3-Kinase and Antiestrogen Resistance in Breast Cancer
Authors: Miller Todd W. , Balko Justin M. , Arteaga Carlos L.
Published: October 2011

Although antiestrogen therapies targeting estrogen receptor (ER) α signaling prevent disease recurrence in the majority of patients with hormone-dependent breast cancer, a significant fraction of patients exhibit de novo or acquired resistance. Currently, the only accepted mechanism linked with endocrine resistance is amplification or overexpression of the ERBB2 (human epidermal growth factor receptor 2 [HER2]) proto-oncogene. Experimental and clinical evidence suggests that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway, the most frequently mutated pathway in breast cancer, promotes antiestrogen resistance. PI3K is a major signaling hub downstream of HER2 and other receptor tyrosine kinases. PI3K activates several molecules involved in cell-cycle progression and survival, and in ER-positive breast cancer cells, it promotes estrogen-dependent and -independent ER transcriptional activity. Preclinical tumor models of antiestrogen-resistant breast cancer often remain sensitive to estrogens and PI3K inhibition, suggesting that simultaneous targeting of the PI3K and ER pathways may be most effective. Herein, we review alterations in the PI3K pathway associated with resistance to endocrine therapy, the state of clinical development of PI3K inhibitors, and strategies for the clinical investigation of such drugs in hormone receptor–positive breast cancer.
Compromised Health-Related Quality of Life in Patients With Low-Grade Glioma
Authors: Aaronson Neil K. , Taphoorn Martin J.B. , Heimans Jan J. , Postma Tjeerd J. , Gundy Chad M. , Beute Guus N. , Slotman Ben J. , Klein Martin
Published: October 2011

Purpose

To investigate the generic and condition-specific health-related quality of life (HRQL) of patients with low-grade glioma (LGG).

Patients and Methods

A total of 195 patients with LGG, which was diagnosed, on average, 5.6 years before the study, were compared with 100 patients with hematologic (non-Hodgkin's) lymphoma and chronic lymphatic leukemia cancer (NHL/CLL) and 205 general population controls who were comparable with patients with LGG at the group level for age, sex, and education (healthy controls). Generic HRQL was assessed with the Short Form-36 (SF-36) Health Survey, and condition-specific HRQL was assessed with the Medical Outcomes Study cognitive function questionnaire and the European Organisation for Research and Treatment of Cancer brain cancer module. Objective neurocognitive functioning was assessed with a standardized battery of neuropsychological tests.

Results

No statistically significant differences were observed between patients with LGG and patients with NHL/CLL in SF-36 scores. Patients with LGG scored significantly lower than healthy controls on six of eight scales and on the mental health component score of the SF-36. Approximately one quarter of patients with LGG reported serious neurocognitive symptoms. Female sex, epilepsy burden, and number of objectively assessed neurocognitive deficits were associated significantly with both generic and condition-specific HRQL. Clinical variables, including the time since diagnosis, tumor lateralization, extent of surgery, and radiotherapy, did not show a consistent relationship with HRQL.

Conclusion

Patients with LGG experienced significant problems across a broad range of HRQL domains, many of which were not condition-specific. However, the neurocognitive deficits and epilepsy that were relatively prevalent among patients with LGG were associated with negative HRQL outcomes and, thus, contributed additionally to the vulnerability of this population of patients with cancer.
Discordance in Perceived Needs Between Patients and Physicians in Oncology Practice: A Nationwide Survey in Korea
Authors: Shin Dong Wook , Kim So Young , Cho Juhee , Sanson-Fisher Robert W. , Guallar Eliseo , Chai Gyu Young , Kim Hak-Soon , Park Bo Ram , Park Eun-Cheol , Park Jong-Hyock
Published: October 2011

Purpose

Identification of supportive care needs in patients with cancer is essential for planning appropriate interventions. We aimed to determine patient–physician concordance in perceived supportive care needs in cancer care and to explore the predictors and potential consequences of patient–physician concordance.

Patients and Methods

A national, multicenter, cross-sectional survey of patient–physician dyads was performed, and 97 oncologists (participation rate, 86.5%) and 495 patients (participation rate, 87.4%) were included. A short form of the Comprehensive Needs Assessment Tool for Cancer Patients was independently administered to patients and their oncologists. Concordance and agreement rates between physicians and patients were calculated. Mixed logistic regression was used to identify predictors of concordance and to explore the association of concordance with patient satisfaction and trust in physicians.

Results

Physicians systematically underestimated patient needs and patient–physician concordance was generally poor, with weighted κ statistics ranging from 0.04 to 0.15 for individual items and Spearman's ρ coefficients ranging from 0.11 to 0.21 for questionnaire domains. Length of experience as oncologist was the only significant predictor of concordance (adjusted odds ratio for overall concordance [aOR] = 2.09; 95% CI, 1.02 to 4.31). Concordance was not significantly associated with overall patient satisfaction (aOR = 1.24; 95% CI, 0.74 to 2.07) or trust in physician (aOR = 1.17; 95% CI, 0.76 to 1.81).

Conclusion

Our findings revealed significant underestimation of patient needs and poor concordance between patients and physicians in assessing perceived needs of supportive care. The clinical implications of this discordance warrant further investigation.
On the ruin probability of the generalised Ornstein–Uhlenbeck process in the cramér case
Authors: Bankovsky Damien , Klüppelberg Claudia , Maller Ross
Published: October 2011

For a bivariate Lévy process (ξt,ηt)t≥ 0 and initial value V0 define the generalised Ornstein–Uhlenbeck (GOU) process Vt:=eξt (V0+∫t0 e-ξs-dηs), t≥0, and the associated stochastic integral process Zt:=∫0t e-ξs-dηs, t≥0. Let Tz:=inf{t>0: Vt<0|V0=z} and ψ(z):=P(Tz<∞) for z≥0 be the ruin time and infinite horizon ruin probability of the GOU process. Our results extend previous work of Nyrhinen (2001) and others to give asymptotic estimates for ψ(z) and the distribution of Tz as z→∞, under very general, easily checkable, assumptions, when ξ satisfies a Cramér condition.
Ruin probabilities in a diffusion environment
Authors: Grandell Jan , Schmidli Hanspeter
Published: October 2011

We consider an insurance model, where the underlying point process is a Cox process. Using a martingale approach applied to diffusion processes, finite-time Lundberg inequalities are obtained. By change-of-measure techniques, Cramér–Lundberg approximations are derived.
Asymptotics of conditional moments of the summand in Poisson compounds
Authors: Rolski Tomasz , Tomanek Agata
Published: October 2011

Suppose that N is a ℤ+-valued random variable and that X,X1,X2,… is a sequence of independent and identically distributed ℤ+ random variables independent of N. In this paper we are interested in properties of the conditional variable In particular, we want to know the asymptotic behavior of the conditional mean ENk or the conditional variance varNk as k→∞. We consider the cases when X is Poisson and when X is mixed Poisson. The problem is motivated by modeling loss reserves in nonlife insurance.
A comparison of cross-entropy and variance minimization strategies
Authors: Chan Joshua C. C. , Glynn Peter W. , Kroese Dirk P.
Published: October 2011

The variance minimization (VM) and cross-entropy (CE) methods are two versatile adaptive importance sampling procedures that have been successfully applied to a wide variety of difficult rare-event estimation problems. We compare these two methods via various examples where the optimal VM and CE importance densities can be obtained analytically. We find that in the cases studied both VM and CE methods prescribe the same importance sampling parameters, suggesting that the criterion of minimizing the CE distance is very close, if not asymptotically identical, to minimizing the variance of the associated importance sampling estimator.
The size of a major epidemic of a vector-borne disease
Authors: Daley Daryl J. , Swift Randall J.
Published: October 2011

Based on a simple model due to Dietz, it is shown that the size of a major epidemic of a vector-borne disease with basic reproduction ratio R0>1 is dominated by the size of a standard SIR (susceptible–infected–removed) epidemic with direct host-to-host transmission of disease and the same R0. Further bounds and numerical illustrations are provided, broadly spanning situations where the size of the epidemic is short of infecting almost all those susceptible. The total size is moderately sensitive to changes in the population parameters that contribute to R0, so that the fluctuating behaviour in ‘annual’ epidemics is not surprising.
Asymptotic normality of M-estimators in nonhomogeneous hidden Markov models
Authors: Jensen Jens Ledet
Published: October 2011

Results on asymptotic normality for the maximum likelihood estimate in hidden Markov models are extended in two directions. The stationarity assumption is relaxed, which allows for a covariate process influencing the hidden Markov process. Furthermore, a class of estimating equations is considered instead of the maximum likelihood estimate. The basic ingredients are mixing properties of the process and a general central limit theorem for weakly dependent variables.
Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3
Authors: Gore Aniket V. , Swift Matthew R. , Cha Young R. , Lo Brigid , McKinney Mary C. , Li Wenling , Castranova Daniel , Davis Andrew , Mukouyama Yoh-suke , Weinstein Brant M.
Published: October 2011

Here, we show that a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway plays an essential role in developmental angiogenesis. A mutation in R-spondin1 (rspo1), a Wnt signaling regulator, was uncovered during a forward-genetic screen for angiogenesis-deficient mutants in the zebrafish. Embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis. Endothelial cell-autonomous inhibition of canonical Wnt signaling also blocks angiogenesis in vivo. The pro-angiogenic effects of Rspo1/Wnt signaling are mediated by Vegfc/Vegfr3(Flt4) signaling. Vegfc expression is dependent on Rspo1 and Wnt, and Vegfc and Vegfr3 are necessary to promote angiogenesis downstream from Rspo1-Wnt. As all of these molecules are expressed by the endothelium during sprouting stages, these results suggest that Rspo1-Wnt-VegfC-Vegfr3 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis.
The cytoskeletal regulator Genghis khan is required for columnar target specificity in theDrosophilavisual system
Authors: Gontang Allison C. , Hwa Jennifer J. , Mast Joshua D. , Schwabe Tina , Clandinin Thomas R.
Published: October 2011

A defining characteristic of neuronal cell type is the growth of axons and dendrites into specific layers and columns of the brain. Although differences in cell surface receptors and adhesion molecules are known to cause differences in synaptic specificity, differences in downstream signaling mechanisms that determine cell type-appropriate targeting patterns are unknown. Using a forward genetic screen in Drosophila, we identify the GTPase effector Genghis khan (Gek) as playing a crucial role in the ability of a subset of photoreceptor (R cell) axons to innervate appropriate target columns. In particular, single-cell mosaic analyses demonstrate that R cell growth cones lacking Gek function grow to the appropriate ganglion, but frequently fail to innervate the correct target column. Further studies reveal that R cell axons lacking the activity of the small GTPase Cdc42 display similar defects, providing evidence that these proteins regulate a common set of processes. Gek is expressed in all R cells, and a detailed structure-function analysis reveals a set of regulatory domains with activities that restrict Gek function to the growth cone. Although Gek does not normally regulate layer-specific targeting, ectopic expression of Gek is sufficient to alter the targeting choices made by another R cell type, the targeting of which is normally Gek independent. Thus, specific regulation of cytoskeletal responses to targeting cues is necessary for cell type-appropriate synaptic specificity.
Apolipoprotein B100 is a better treatment target than calculated LDL and non-HDL cholesterol in statin-treated patients
Authors: Soran Handrean , France Michael W , Kwok See , Dissanayake Sanjaya , Charlton-Menys Valentine , Younis Nahla N , Durrington Paul N
Published: October 2011

Introduction

Clinical trials have shown that apolipoprotein B100 (apoB) is better than calculated low-density lipoprotein cholesterol (c-LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) as a target for statin treatment. However, there are no published reports of how well these targets are reached in patients with more severe hyperlipidaemias than represented in trials, as seen in lipid clinics.

Methods

We audited 195 patients attending a tertiary centre lipid clinic, who had been treated with a statin for more than one year. We measured total cholesterol, HDL-cholesterol (HDL-C) and triglyceride and from these calculated LDL-cholesterol (LDL-C) and non-HDL-C. We determined the average measured apoB values, at critical target values of LDL-C and non-HDL-C, by linear regression and compared them with values of apoB considered equivalent to these cholesterol indexes by expert groups. We also assessed the number of patients, both before and after treatment, in whom c-LDL-C and non-HDL-C could not be calculated due to hypertriglyceridaemia.

Results

At the LDL-C target of 2.6 mmol L−1 and the non-HDL-C target of 3.4 mmol L−1, the measured apoB values were significantly higher than consensus apoB target values. The difference was most marked for c-LDL-C in hypertriglyceridaemic subjects and for non-HDL-C in patients without hypertriglyceridaemia. A similar pattern was seen using centile-derived consensus values but the differences were accentuated because this approach generates lower equivalent consensus apoB values.

Conclusion

ApoB offers a more consistent treatment target independent of hypertriglyceridaemia and would obviate technical problems related to high triglycerides.
The need for innovative sexually transmitted infection screening initiatives for young men: evidence from genitourinary medicine clinics across England
Authors: Dave S S , French R S , Jungmann E , Brook G , Cassell J A , Mercer C H
Published: October 2011

The study objectives were to ascertain behavioural, access-related, health-seeking factors and sexually transmitted infection (STI) prevalence in young men (<25 years) attending genitourinary (GU) medicine clinics and compare them with older men (≥25 years) and young women (<25 years). Between October 2004 and March 2005, 4600 new attendees at seven sociodemographically and geographically contrasting GU medicine clinics across England completed questionnaires, which were linked to routine clinical data. Young men waited significantly less time to be seen in clinic compared with older men and young women. They were less likely to report symptoms than older men ( P = 0.021) yet more likely to be diagnosed with chlamydia ( P = 0.001) and gonorrhoea ( P = 0.007). They were also more likely to be diagnosed with an acute STI relative to young women ( P = 0.007). Our data confirm the need to make comprehensive STI screening readily available for young men and to develop effective and innovative screening strategies in different settings.
High uptake of hepatitis C virus treatment in HIV/hepatitis C virus co-infected patients attending an integrated HIV/hepatitis C virus clinic
Authors: Kieran J , Dillon A , Farrell G , Jackson A , Norris S , Mulcahy F , Bergin C
Published: October 2011

Hepatitis C virus (HCV) is a major cause of liver disease in HIV-infected patients. The HCV treatment outcomes and barriers to HCV referral were examined in a centre with a HIV/HCV co-infection clinic. Patients who were antibody positive for both HIV and HCV between 1987 and January 2009 were identified. A retrospective chart review was undertaken. Multivariate analysis was performed to assess predictors of HCV clinic referral. Data were collected on 386 HIV/HCV patients; 202/386 had been referred to the co-infection clinic and 107/202 had HCV treatment. In addition, 29/202 were undergoing pretreatment work-up. Overall sustained virologic response (SVR) was 44%; SVR was equivalent in those who acquired HIV/HCV infection from intravenous drug use (IDU) and others. On multivariate analysis, patients who missed appointments, were younger, with active IDU and advanced HIV and who were not offered HCV treatment were less likely to be referred to the clinic. Patients attending the clinic were more likely to have been screened for hepatocellular carcinoma than those attending the general HIV service. Two-thirds of patients referred to the clinic had engaged with the HCV treatment programme. Dedicated co-infection clinics lower the threshold for treatment and improve management of liver disease in co-infected patients.
Can plasma HHV8 viral load be used to differentiate multicentric Castleman disease from Kaposi sarcoma?
Authors: Sayer R , Paul J , Tuke P W , Hargreaves S , Noursadeghi M , Tedder R S , Grant P , Edwards S G , Miller R F
Published: October 2011

We measured plasma human herpesvirus 8 (HHV8) DNA load in consecutive patients presenting with HIV-associated multicentric Castleman disease (MCD) and in contemporaneous patients who had Kaposi sarcoma (KS), lymphoma or other diagnoses. All 11 patients with MCD had detectable plasma HHV8 DNA compared with 18 (72%) of 25 patients with KS, none with lymphoma and one of 38 patients with other diagnoses. Detectable plasma HHV8 DNA levels were higher among MCD patients, median (interquartile range [IQR]) = 43,500 (5200–150,000) copies/mL, when compared with those with KS, median (IQR) = 320 (167–822) copies/mL and those with lymphoma and other diagnoses (one-way analysis of variance; P = 0.0303). Using receiver operating characteristic analysis, a cut-off of >1000 copies HHV8 DNA/mL of plasma helped to discriminate between MCD and other diagnoses, with a specificity of 94.7% and a negative predictive value of 97.3%. The level of HHV8 viraemia, while not diagnostic, may aid discrimination between patients with MCD and those with KS and other systemic illnesses.
HIV encephalitis despite suppressed viraemia: a case of compartmentalized viral escape
Authors: Bingham R , Ahmed N , Rangi P , Johnson M , Tyrer M , Green J
Published: October 2011

There is increasing concern that HIV treatment failure may result from inadequate central nervous system (CNS) penetration of antiretroviral drugs, allowing compartmentalized viral replication and development of resistance. We discuss a patient who maintained a suppressed plasma viral load for four years on antiretroviral therapy (ART) before developing HIV encephalitis with a cerebrospinal fluid (CSF) HIV viral load of 861 copies/mL and newly detectable plasma viral load of 68 copies/mL. Identification of major resistance mutations to his combination therapy supported concerns that resistant HIV had developed within the CNS. His ART was changed to optimize CNS penetration, leading to maintained clinical improvement. Imaging presented demonstrates corresponding radiological improvement. The report illustrates the need to exclude CNS viral rebound or incomplete suppression in HIV patients with neurological symptoms, and suggests that the extent of this emerging problem is only beginning to be recognized as the implications of long-term peripheral HIV suppression unfold.
UK national guideline for the management of gonorrhoea in adults, 2011
Authors: Bignell C , FitzGerald M ,   (Guideline Development Group)
Published: October 2011

The British Association for Sexual Health and HIV (BASHH) UK gonorrhoea guideline has been updated in 2011. It offers advice on diagnosis, treatment and health promotion for anogenital and pharyngeal gonorrhoea. Nucleic acid amplification tests (NAATs) are now being used more for diagnosis and are increasing detection rates in the pharynx and rectum. First line treatment using ceftriaxone with azithromycin is now advised, along with routine test of cure (TOC). The aim is to slow the spread of resistant gonorrhoea now that fewer antibiotics remain effective. A patient information leaflet has been developed.
A New Graph-Theoretical Model for the Guillotine-Cutting Problem
Authors: Clautiaux François , Jouglet Antoine , Moukrim Aziz
Published: October 2011

We consider the problem of determining whether a given set of rectangular items can be cut from a larger rectangle using so-called guillotine cuts only. We introduce a new class of arc-colored directed graphs called guillotine graphs and show that each guillotine graph can be associated with a specific class of pattern solutions that we call a guillotine-cutting class. The properties of guillotine graphs are examined, and some effective algorithms for dealing with guillotine graphs are proposed. As an application, we then describe a constraint programming method based on guillotine graphs, and we propose effective filtering techniques that use the graph model properties in order to reduce the search space efficiently. Computational experiments are reported on benchmarks from the literature: our algorithm outperforms previous methods when solving the most difficult instances exactly.
The Generalized Covering Salesman Problem
Authors: Golden Bruce , Naji-Azimi Zahra , Raghavan S. , Salari Majid , Toth Paolo
Published: October 2011

Given a graph G = (N, E), the covering salesman problem (CSP) is to identify the minimum length tour “covering” all the nodes. More specifically, it seeks the minimum-length tour visiting a subset of the nodes in N such that each node i not on the tour is within a predetermined distance di of a node on the tour. In this paper, we define and develop a generalized version of the CSP, and we refer to it as the generalized covering salesman problem (GCSP). Here, each node i needs to be covered at least ki times, and there is a cost associated with visiting each node. We seek a minimum-cost tour such that each node i is covered at least ki times by the tour. We define three variants of the GCSP. In the first case, each node can be visited by the tour at most once. In the second case, visiting a node i more than once is possible, but an overnight stay is not allowed (i.e., to revisit a node i, the tour has to visit another node before it can return to i). Finally, in the third case, the tour can visit each node more than once consecutively. In this paper, we develop two local search heuristics to find high-quality solutions to the three GCSP variants. To test the proposed algorithms, we generated data sets based on traveling salesman problem library instances. Because the CSP and the generalized traveling salesman problem are special cases of the GCSP, we tested our heuristics on both of those problems as well. Overall, the results show that our proposed heuristics find high-quality solutions very rapidly.