bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosticators and Risk Grouping in Patients with Lung Metastasis from Nasopharyngeal Carcinoma: A more accurate and appropriate assessment of prognosis
Authors: Cao Xun , Luo Rong-Zhen , He Li-Ru , Li Yong , Lin Wen-Qian , Chen You-Fang , Wen Zhe-Sheng
Published: August 2011

Background

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC.

Methods

A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves.

Results

The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%.

Conclusions

In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.
Alzheimer's disease: synapses gone cold
Authors: Koffie Robert M , Hyman Bradley T , Spires-Jones Tara L
Published: August 2011

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by insidious cognitive decline and memory dysfunction. Synapse loss is the best pathological correlate of cognitive decline in AD and mounting evidence suggests that AD is primarily a disease of synaptic dysfunction. Soluble oligomeric forms of amyloid beta (Aβ), the peptide that aggregates to form senile plaques in the brain of AD patients, have been shown to be toxic to neuronal synapses both in vitro and in vivo. Aβ oligomers inhibit long-term potentiation (LTP) and facilitate long-term depression (LTD), electrophysiological correlates of memory formation. Furthermore, oligomeric Aβ has also been shown to induce synapse loss and cognitive impairment in animals. The molecular underpinnings of these observations are now being elucidated, and may provide clear therapeutic targets for effectively treating the disease. Here, we review recent findings concerning AD pathogenesis with a particular focus on how Aβ impacts synapses.
Compliance with eight years of annual ivermectin treatment of onchocerciasis in Cameroon and Nigeria
Authors: Brieger William R , Okeibunor Joseph C , Abiose Adenike O , Wanji Samuel , Elhassan Elizabeth , Ndyomugyenyi Richard , Amazigo Uche V
Published: August 2011

Background

As the African Programme for Onchocerciasis Control (APOC) matured into its 10th year of ensuring community involvement in mass annual treatment of onchocerciasis with ivermectin, there was recognition of a need to study not only annual coverage of ivermectin in villages but also the compliance of individual villagers with these annual treatments. This was based on the concern that while population coverage goals may be achieved each year, there might be segments of the population who systematically are not complying with the annual regimen, thus creating a reservoir of infection and threatening program gains.

Methods

A multi-site study in five APOC sponsored projects in Nigeria and Cameroon was undertaken to identify the socio-demographic correlates of compliance with ivermectin treatment. A total of 8,480 villagers above 9 years of age selected through a systematic random sampling from 101 communities were surveyed to ascertain their levels of compliance, by adapting APOC's standard household ivermectin survey form. Community leaders, community directed distributors (CDDs) of ivermectin and health workers were interviewed with in-depth interview guides, while focus group discussions were held with community members to help explain how socio-demographic factors might affect compliance.

Results

Eight-year compliance ranged from 0 to 8 times with 42.9% taking ivermectin between 6-8 times annually (high compliance). In bivariate analysis high compliance was positively associated with being male, over 24 years of age, having been married, not being Christian, having little or no formal education and being in the ethnic majority. These variables were also confirmed through regression analysis based on total times ivermectin was taken over the period. While these factors explained only 8% of the overall variation in compliance, ethnic status and education appeared to be the strongest factors. Those with higher education may be more mobile and harder to reach while neglect of ethnic minorities has also been documented in other programs.

Conclusion

These findings can help managers of CDTI programmes to ensure ivermectin reaches all segments of the population equally.
Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization
Authors: Ramírez César A , Requena José M , Puerta Concepción J
Published: August 2011

Background

The heat stress suffered by Leishmania sp during its digenetic life-cycle is a key trigger for its stage differentiation. In Leishmania subgenera two classes of HSP70 genes differing in their 3' UTR were described. Although the presence of HSP70-I genes was previously suggested in Leishmania (Viannia) braziliensis, HSP70-II genes had been reluctant to be uncovered.

Results

Here, we report the existence of two types of HSP70 genes in L. braziliensis and the genomic organization of the HSP70 locus. RT-PCR experiments were used to map the untranslated regions (UTR) of both types of genes. The 3' UTR-II has a low sequence identity (55-57%) when compared with this region in other Leishmania species. In contrast, the 5' UTR, common to both types of genes, and the 3' UTR-I were found to be highly conserved among all Leishmania species (77-81%). Southern blot assays suggested that L. braziliensis
HSP70 gene cluster may contain around 6 tandemly-repeated HSP70-I genes followed by one HSP70-II gene, located at chromosome 28. Northern blot analysis indicated that levels of both types of mRNAs are not affected by heat shock.

Conclusions

This study has led to establishing the composition and structure of the HSP70 locus of L. braziliensis, complementing the information available in the GeneDB genome database for this species. L. braziliensis
HSP70 gene regulation does not seem to operate by mRNA stabilization as occurs in other Leishmania species.
Association of acid phosphatase locus 1*Callele with the risk of cardiovascular events in rheumatoid arthritis patients
Authors: Teruel María , Martin Jose-Ezequiel , González-Juanatey Carlos , López-Mejias Raquel , Miranda-Filloy Jose A , Blanco Ricardo , Balsa Alejandro , Pascual-Salcedo Dora , Rodriguez-Rodriguez Luis , Fernández-Gutierrez Benjamin , Ortiz Ana M , González-Alvaro Isidoro , Gómez-Vaquero Carmen , Bottini Nunzio , Llorca Javier , González-Gay Miguel A , Martin Javier
Published: August 2011

Introduction

Acid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell. The aim of this study was to determine the contribution of ACP1 polymorphisms to susceptibility to rheumatoid arthritis (RA), as well as the potential contribution of these polymorphisms to the increased risk of cardiovascular disease (CV) observed in RA patients.

Methods

A set of 1,603 Spanish RA patients and 1,877 healthy controls were included in the study. Information related to the presence/absence of CV events was obtained from 1,284 of these participants. All individuals were genotyped for four ACP1 single-nucleotide polymorphisms (SNPs), rs10167992, rs11553742, rs7576247, and rs3828329, using a predesigned TaqMan SNP genotyping assay. Classical ACP1 alleles (*A, *B and *C) were imputed with SNP data.

Results

No association between ACP1 gene polymorphisms and susceptibility to RA was observed. However, when RA patients were stratified according to the presence or absence of CV events, an association between rs11553742*T and CV events was found (P = 0.012, odds ratio (OR) = 2.62 (1.24 to 5.53)). Likewise, the ACP1*C allele showed evidence of association with CV events in patients with RA (P = 0.024, OR = 2.43).

Conclusions

Our data show that the ACP1*C allele influences the risk of CV events in patients with RA.
High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts
Authors: Wähämaa Heidi , Schierbeck Hanna , Hreggvidsdottir Hulda S , Palmblad Karin , Aveberger Anne-Charlotte , Andersson Ulf , Harris Helena Erlandsson
Published: August 2011

Introduction

In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other proinflammatory molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through the formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it is suggested to promote inflammation as intra-articular injections of HMGB1 induce synovitis in mice and HMGB1 neutralizing therapy suppresses development of experimental arthritis. The aim of this study was to determine whether HMGB1 in complex with LPS, interleukin (IL)-1α or IL-1β has enhancing effects on the production of proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll-like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects of the investigated HMGB1-ligand complexes.

Methods

Synovial fibroblasts obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were stimulated with HMGB1 alone or in complex with LPS, IL-1α or IL-1β. Tumour necrosis factor (TNF) production was determined by enzyme-linked immunospot assay (ELISPOT) assessment. Levels of IL-10, IL-1-β, IL-6 and IL-8 were measured using Cytokine Bead Array and matrix metalloproteinase (MMP) 3 production was determined by ELISA.

Results

Stimulation with HMGB1 in complex with LPS, IL-1α or IL-1β enhanced production of TNF, IL-6 and IL-8. HMGB1 in complex with IL-1β increased MMP production from both RASF and OASF. The cytokine production was inhibited by specific receptor blockade using detoxified LPS or IL-1 receptor antagonist, indicating that the synergistic effects were mediated through the partner ligand-reciprocal receptors TLR4 and IL-1RI, respectively.

Conclusions

HMGB1 in complex with LPS, IL-1α or IL-1β boosted proinflammatory cytokine- and MMP production in synovial fibroblasts from RA and OA patients. A mechanism for the pathogenic role of HMGB1 in arthritis could thus be through enhancement of inflammatory and destructive mechanisms induced by other proinflammatory mediators present in the arthritic joint.
sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy
Authors: Arabi Yaseen M , Dehbi Mohammed , Rishu Asgar H , Baturcam Engin , Kahoul Salim H , Brits Riette J , Naidu Brintha , Bouchama Abderrezak
Published: August 2011

Introduction

Hyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE).

Methods

A predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.

Results

Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.

Conclusions

These findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.
Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis
Authors: Zaragosi Laure-Emmanuelle , Wdziekonski Brigitte , Brigand Kevin Le , Villageois Phi , Mari Bernard , Waldmann Rainer , Dani Christian , Barbry Pascal
Published: August 2011

Background

In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation.

Results

We used deep sequencing to identify small RNAs that are differentially expressed during adipogenesis of adipose tissue-derived stem cells. This approach revealed the un-annotated miR-642a-3p as a highly adipocyte-specific miRNA. We then focused our study on the miR-30 family, which was also up-regulated during adipogenic differentiation and for which the role in adipogenesis had not yet been elucidated. Inhibition of the miR-30 family blocked adipogenesis, whilst over-expression of miR-30a and miR-30d stimulated this process. We additionally showed that both miR-30a and miR-30d target the transcription factor RUNX2, and stimulate adipogenesis via the modulation of this major regulator of osteogenesis.

Conclusions

Overall, our data suggest that the miR-30 family plays a central role in adipocyte development. Moreover, as adipose tissue-derived stem cells can differentiate into either adipocytes or osteoblasts, the down-regulation of the osteogenesis regulator RUNX2 represents a plausible mechanism by which miR-30 miRNAs may contribute to adipogenic differentiation of adipose tissue-derived stem cells.
Hair testing is taking root
Authors: Cooper Gail Audrey Ann
Published: August 2011

An increasing number of toxicology laboratories are choosing to expand the services they offer to include hair testing in response to customer demands. Hair provides the toxicologist with many advantages over conventional matrices in that it is easy to collect, is a robust and stable matrix that does not require refrigeration, and most importantly, provides a historical profile of an individual's exposure to drugs or analytes of interest. The establishment of hair as a complementary technique in forensic toxicology is a direct result of the success of the matrix in medicolegal cases and the wide range of applications. However, before introducing hair testing, laboratories must consider what additional requirements they will need that extend beyond simply adapting methodologies already validated for blood or urine. Hair presents many challenges with respect to the lack of available quality control materials, extensive sample handling protocols and low drug concentrations requiring greater instrument sensitivity. Unfortunately, a common pitfall involves over-interpretation of the findings and must be avoided.
Perception, satisfaction and utilization of the VALUE home telehealth service
Authors: Finkelstein Stanley M , Speedie Stuart M , Zhou Xinyu , Potthoff Sandra , Ratner Edward R
Published: August 2011

We conducted a randomized controlled trial to evaluate the perception, satisfaction and utilization of a home telehealth service for frail elderly people living independently in their home communities. Control group subjects continued with their usual care and intervention group subjects were able to supplement their usual care with the use of a web portal. The web portal allowed videoconferencing and electronic messaging between home care nurses and clients, ordering health-related and home care services, access to health-related information and general access to the Internet. A total of 99 eligible people (59 female, 40 male) from one urban and one rural study site agreed to participate in the study. Eighty-four subjects were active participants for nine months. There were no significant differences in perception of technology between the two groups at baseline. At 60-day follow-up, the intervention group was significantly more positive towards technology compared to their own baseline ( P < 0.001) and compared to the 60-day scores for the controls ( P < 0.001). The intervention group indicated that overall the telehealth service met their expectations (mean score 9 out of 10) and they would recommend it to others (mean score 9.5 out of 10). All subjects were able to use the portal without difficulty after brief instructions from the nurses. A total of 1054 videoconferences were conducted with the intervention subjects. Fifty-six of these (5%) had to be discontinued after successful connection because of technical problems. Intervention subjects made fewer emergency department visits than control subjects, more visits to the eye doctor, fewer visits in all categories of home care utilization, and lower use of transportation services. Frail elderly people are able to adopt home telehealth technologies which may enable them to maintain independent living arrangements.
A telepsychiatry transition clinic: the first 12 months experience
Authors: Detweiler Mark B , Arif Saira , Candelario Joseph , Altman Joanne , Murphy Pamela F , Halling Mary H , Detweiler Jonna G , Vasudeva Sachinder
Published: August 2011

To improve the management of soldiers with combat-related mental health problems, an interdisciplinary telepsychiatry service was established between a clinic at the Fort Bragg army base and the Veterans Affairs (VA) Medical Center in Salem. In the first 12 months of operation, 120 soldiers (105 males) were seen in a total of 394 telepsychiatry sessions. The time spent on telepsychiatry by the six VA psychiatrists increased from 13 hours in the first month to 41 hours in the twelfth month. The number of telepsychiatry sessions increased from nine in the first month to 56 in the twelfth month. The mean global assessment of function score (GAF) in the soldiers increased significantly ( P < 0.001) from 58.0 at intake to 62.3 at the last visit. Soldiers received VA telepsychiatry on average 22 days after the initial consultation with a primary care provider, a reduction of at least eight days compared to the previous delay. The majority of soldiers (89%) who were treated by VA psychiatrists enrolled in the VA within about six months of discharge. Similar VA-US Military collaborations may prove beneficial for other military bases that have returning combat soldiers.
Automated home telephone self-monitoring reduces hospitalization in patients with advanced heart failure
Authors: Kurtz Baptiste , Lemercier Mathieu , Pouchin Sophie Cordier , Benmokhtar Emmanuelle , Vallet Charlotte , Cribier Alain , Bauer Fabrice
Published: August 2011

We studied 138 patients admitted for heart failure (HF). Patients were allocated one of three treatment strategies. Group 1 (G1, n = 50) were given usual care for HF, Group 2 (G2, n = 56) received a multi-disciplinary team approach, while Group 3 (G3, n = 32) had home telephone self-monitoring. Telemonitoring was based on the answers to three simple queries about bodyweight change, dyspnoea and general health. The system stratified the HF severity of each patient once a week, and recommended a prompt medical appointment or simple follow-up. Over a 12-month follow-up period, there were 43 adverse events (cardiovascular deaths and rehospitalizations for HF: G1 = 22, G2 = 14, G3 = 7). There was no difference between G2 and G3 ( P = 0.78) but there was significant disadvantage with usual care ( P = 0.02 vs. G2 and P = 0.04 vs. G3). Time to re-admission for HF increased in G2 and G3 compared to G1 (188 and 198 days vs. 95 days, P = 0.03 and P = 0.02 respectively). Automated home telephone self-monitoring reduced rehospitalization in patients with advanced HF.
Trial of a mobile phone method for recording dietary intake in adults with type 2 diabetes: evaluation and implications for future applications
Authors: Rollo Megan E , Ash Susan , Lyons-Wall Philippa , Russell Anthony
Published: August 2011

We evaluated a mobile phone application (Nutricam) for recording dietary intake. It allowed users to capture a photograph of food items before consumption and store a voice recording to explain the contents of the photograph. This information was then sent to a website where it was analysed by a dietitian. Ten adults with type 2 diabetes (BMI 24.1–47.9 kg/m2) recorded their intake over a three-day period using both Nutricam and a written food diary. Compared to the food diary, energy intake was under-recorded by 649 kJ (SD 810) using the mobile phone method. However, there was no trend in the difference between dietary assessment methods at levels of low or high energy intake. All subjects reported that the mobile phone system was easy to use. Six subjects found that the time taken to record using Nutricam was shorter than recording using the written diary, while two reported that it was about the same. The level of detail provided in the voice recording and food items obscured in photographs reduced the quality of the mobile phone records. Although some modifications to the mobile phone method will be necessary to improve the accuracy of self-reported intake, the system was considered an acceptable alternative to written records and has the potential to be used by adults with type 2 diabetes for monitoring dietary intake by a dietitian.
Mobile computing and the quality of home care nursing practice
Authors: Paré Guy , Sicotte Claude , Moreault Marie-Pierre , Poba-Nzaou Placide , Nahas Georgette , Templier Mathieu
Published: August 2011

We investigated the effects of the introduction of mobile computing on the quality of home care nursing practice in Québec. The software, which structured and organized the nursing activities in patients' homes, was installed sequentially in nine community health centres. The completeness of the nursing notes was compared in 77 paper records (pre-implementation) and 73 electronic records (post-implementation). Overall, the introduction of the software was associated with an improvement in the completeness of the nursing notes. All 137 nurse users were asked to complete a structured questionnaire. A total of 101 completed questionnaires were returned (74% response rate). Overall, the nurses reported a very high level of satisfaction with the quality of clinical information collected. A total of 57 semi-structured interviews were conducted and most nurses believed that the new software represented a user-friendly tool with a clear and understandable structure. A postal questionnaire was sent to approximately 1240 patients. A total of 223 patients returned the questionnaire (approximately 18% response rate). Overall, patients felt that the use of mobile computing during home visits allowed nurses to manage their health condition better and, hence, provide superior care services. The use of mobile computing had positive and significant effects on the quality of care provided by home nurses.
Teleconsultation via the web: an analysis of the type of questions that Iranian patients ask
Authors: Deldar Kolsum , Marouzi Parviz , Assadi Reza
Published: August 2011

We evaluated an ask-the-doctor service which was set up as one of the accessory services of a health education website in Iran. The study lasted for five months. A total of 500 enquiries were submitted to the question and answer system. Eighty enquiries were excluded because they were duplicated submissions, not replied to by doctors or gave insufficient information for a reply. Most enquirers (33%) were female and aged 21–35 years. The most frequently asked questions were about embarrassing and sensitive topics, particularly on women's health and mental health. The majority of the questions were submitted on behalf of the enquirers themselves, with only 13% asking for others (children, parents, friends). Although there are various problems associated with online consultation, it does at least overcome one of the great drawbacks of some cultures, where people are reluctant to talk openly about certain matters, even with their doctors.
Managing suicidality in home-based telehealth
Authors: Gros Daniel F , Veronee Kimberly , Strachan Martha , Ruggiero Kenneth J , Acierno Ron
Published: August 2011

We describe the case of a US veteran from the war in Afghanistan with post-traumatic stress disorder (PTSD). The patient was undergoing treatment at home via telehealth as part of a research trial. In week six, he presented with severe suicidal ideation and required emergency hospitalization. Through a series of immediate enhanced communications (i.e. by videoconference) between the patient, patient's family, treatment team and local resources, the patient's symptoms were assessed to identify suicidality and an intervention was successfully carried out, involving the development of a safety plan and eventual transportation to an inpatient unit at the local Veterans Administration Medical Center, where he was hospitalized for three days. This demonstrates the value of telehealth in identifying and treating severe psychiatric symptoms in addition to supporting the safety of these procedures to address suicidality.
Finite-Sample Performance of Absolute Precision Stopping Rules
Authors: Singham Dashi I. , Schruben Lee W.
Published: August 2011

Absolute precision stopping rules are often used to determine the length of sequential experiments to estimate confidence intervals for simulated performance measures. Much is known about the asymptotic behavior of such procedures. In this paper, we introduce coverage contours to quantify the trade-offs in interval coverage, stopping times, and precision for finite-sample experiments using absolute precision rules. We use these contours to evaluate the coverage of a basic absolute precision stopping rule, and we show that this rule will lead to a bias in coverage even if all of the assumptions supporting the procedure are true. We define optimal stopping rules that deliver nominal coverage with the smallest expected number of observations. Contrary to previous asymptotic results that suggest decreasing the precision of the rule to approach nominal coverage in the limit, we find that it is optimal to increase the confidence coefficient used in the stopping rule, thus obtaining nominal coverage in a finite-sample experiment. If the simulation data are independent and identically normally distributed, we can calculate coverage contours analytically and find a stopping rule that is insensitive to the variance of the data while delivering at least nominal coverage for any precision value.
Sequential and Temporal Dynamics of Online Opinion
Authors: Godes David , Silva José C.
Published: August 2011

We investigate the evolution of online ratings over time and sequence. We first establish that there exist two distinct dynamic processes, one as a function of the amount of time a book has been available for review and another as a function of the sequence of reviews themselves. We find that, once we control for calendar date, the residual average temporal pattern is increasing. This is counter to existing findings that suggest that without this calendar-date control, the pattern is decreasing. With respect to sequential dynamics, we find that ratings decrease: the nth rating is, on average, lower than the n-1th when controlling for time, reviewer effects, and book effects. We test and find some support for existing theories for this decline based on motivation. We then offer two additional explanations for this “order effect.” We find support for the idea that one's ability to assess the diagnosticity of previous reviews decreases: when previous reviewers are very different, more reviews may thus lead to more purchase errors and lower ratings.
Assessing the Effect of Marketing Investments in a Business Marketing Context
Authors: Kumar V. , Sriram S. , Luo Anita , Chintagunta Pradeep K.
Published: August 2011

Recent research has empirically characterized the buyer–seller relationship as dynamically evolving from one discrete state to another. Conventional wisdom would suggest that a customer in a higher relationship state that has a higher transaction value would also have greater lifetime value to the firm. However, recent evidence suggests that higher relationship states can be ephemeral. Hence, the link between transaction value and lifetime value is not obvious. In this study, we seek to understand, within a specific empirical context, (i) the relationship between a customer's transaction value and that customer's lifetime value and (ii) the relationship between the lifetime value of a customer and the optimal level of marketing activity that needs to be directed at that customer. To this end, we develop a trivariate Tobit hidden Markov model that allows for (a) transitions among relationship states, (b) possible synergies between the various products that the supplier firm offers, (c) endogeneity in marketing activity, (d) heterogeneity in model parameters, and (e) the presence of the no-purchase option. Our results reinforce recent findings by Schweidel et al. [Schweidel, D. A., E. T. Bradlow, P. S. Fader. 2011. Portfolio dynamics for customers of a multiservice provider. Management Sci. 57(3) 471–486] that higher relationship states can be short-lived. Importantly for the supplier firm, a customer in the highest relationship state in a given period does not yield the highest lifetime value to the firm. Hence, the relationship between transaction value (i.e., relationship state) and lifetime value can be nonmonotonic. At the same time, we also find a nonmonotonic relationship between the optimal expenditures that should be directed at a customer and that customer's lifetime value; i.e., the optimal level of marketing contacts is not the highest for customers with the highest lifetime value. Furthermore, we find that the optimal marketing expenditures for myopic agents are 14%–33% lower than the corresponding values for forward-looking agents. Therefore, not accounting for the long-term effects of marketing contacts would lead to suboptimal marketing budgets. Moreover, a comparison with the current marketing expenditures suggests that the current practice is closer to the myopic policy than to the forward-looking one.
Modeling Customer Lifetimes with Multiple Causes of Churn
Authors: Braun Michael , Schweidel David A.
Published: August 2011

Customer retention and customer churn are key metrics of interest to marketers, but little attention has been placed on linking the different reasons for which customers churn to their value to a contractual service provider. In this paper, we put forth a hierarchical competing-risk model to jointly model when customers choose to terminate their service and why. Some of these reasons for churn can be influenced by the firm (e.g., service problems or price–value trade-offs), but others are uncontrollable (e.g., customer relocation and death). Using this framework, we demonstrate that the impact of a firm's efforts to reduce customer churn for controllable reasons is mitigated by the prevalence of uncontrollable ones, resulting in a “damper effect” on the return from a firm's retention marketing efforts. We use data from a provider of land-based telecommunication services to demonstrate how the competing-risk model can be used to derive a measure of the incremental customer value that a firm can expect to accrue through its efforts to delay churn, taking this damper effect into account. In addition to varying across customers based on geodemographic information, the magnitude of the damper effect depends on a customer's tenure to date. We discuss how our framework can be used to tailor the firm's retention strategy to individual customers, both in terms of which customers to target and when retention efforts should be deployed.
Experimental confirmation that vibrations at soft tissue conduction sites induce hearing by way of a new mode of auditory stimulation
Authors: de Jong Marrigje , Perez Ronen , Adelman Cahtia , Chordekar Shai , Rubin Melissa , Kriksunov Leonid , Sohmer Haim
Published: August 2011

Background: A new mode of auditory stimulation has been demonstrated which is through soft tissue conduction (STC). It involves evoking auditory sensations by applying the clinical bone vibrator to the skin over soft tissue (not over bone) sites on the head and neck.

Methods: This study was designed to show that stimulation by STC excites the cochlea in a way similar to that of air conduction (AC) and bone conduction (BC).

Results: It is shown here that auditory nerve brainstem evoked response (ABR) thresholds in mice and in the fat sand rat to AC, to BC and to STC stimulation are all elevated following administration of drugs (salicylic acid and furosemide) which depress the cochlear amplifier. In addition, the present study brings evidence that STC stimulation is not a variant of BC since the sound pressures recorded in the occluded external auditory canal (the occlusion effect) in response to STC are significantly smaller than that to BC stimulation, though both are of equal loudness.

Conclusions: This new mode, STC, therefore appears to bypass the middle ear mechanisms and consequently may contribute to auditory diagnosis.
Determinants of cardiac disease in newly diagnosed patients with acromegaly: results of a 10 year survey study
Authors: Colao Annamaria , Pivonello Rosario , Grasso Ludovica Francesca Stella , Auriemma Renata Simona , Galdiero Mariano , Savastano Silvia , Lombardi Gaetano
Published: August 2011

Context

The most frequent cause of death in acromegaly is cardiomyopathy.

Objective

To evaluate determinants of acromegalic cardiomyopathy.

Design

Observational, open, controlled, retrospective study.

Subjects

Two hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex- and age-matched with the patients.

Main outcome measures

Left ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated.

Results

Compared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total- and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-β. The relative risk to develop mild (odds ratio (OR)=1.67 (1.05–2.66);P=0.027) or severe hypertension (OR=1.58 (1.04–2.32);P=0.027), arrhythmias (OR=4.93 (1.74–15.9);P=0.001), impaired fasting glucose/impaired glucose tolerance (OR=2.65 (1.70–4.13);P<0.0001), diabetes (OR=2.14 (1.34–3.40);P=0.0009), LVH (OR=11.9 (7.4–19.5);P<0.0001), diastolic (OR=3.32 (2.09–5.31);P<0.0001) and systolic dysfunction (OR=14.2 (6.95–32.2);P<0.0001), was higher in acromegaly. The most important predictor of LVH (t=2.4,P=0.02) and systolic dysfunction (t=−2.77,P=0.006) was disease duration and that of diastolic dysfunction was patient's age (t=−3.3,P=0.001). Patients with an estimated disease duration of >10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration ≤5 years.

Conclusions

The prevalence of different features of cardiomyopathy is 3.3–14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.
A case of acromegaly (Greece, 7th century AD)
Authors: Charlier Philippe , Tsigonaki Christina
Published: August 2011

Objective

To diagnose hormone-secreting pituitary adenoma in dry bones.

Design

We present here the case of a pathological skull from the Byzantine site of Eleutherna (Greece).

Methods

A complete anthropological and medical examination of the skull and the whole conserved skeleton was performed in the laboratory.

Results

All anatomical signs of acromegaly were present on this skull. More importantly, enlargement of the sella turcica clearly indicated the development of a macroadenoma, at the origin of the disease.

Conclusions

This skeletal case, and other ancient ones are discussed, to better describe the history of the disease, and the possibilities of the diagnosis.
Quantitative validation of GJC1 promoter hypermethylation in benign and malignant colorectal tumors
Authors: Ahmed Deeqa , Lothe Ragnhild A , Rivedal Edgar , Lind Guro E
Published: August 2011

We have previously shown that the gap junction protein γ 1 (GJC1) gene, encoding the connexin-45 protein, is inactivated by promoter hypermethylation in colorectal cancer. This was confirmed in a recent Endocrine-Related Cancer publication analyzing a limited number of samples. The aim of this study was to analyze GJC1 in a larger clinical cohort (n=485) and to assess whether or not the promoter hypermethylation was associated with clinical or pathological features. The methylation of GJC1 was confirmed to be tumor specific and was observed in 33% of colorectal cancers and 12% of adenomas. The methylation was strongly associated with BRAF mutations (P=5.64×10−13) as well as with proximal tumor location (P=1.42×10−3), features compatible with a CpG island methylator phenotype.
Cost of Adaptation and Fitness Effects of Beneficial Mutations inPseudomonas fluorescens
Authors: Bataillon Thomas , Zhang Tianyi , Kassen Rees
Published: August 2011

Adaptations are constructed through the sequential substitution of beneficial mutations by natural selection. However, the rarity of beneficial mutations has precluded efforts to describe even their most basic properties. Do beneficial mutations typically confer small or large fitness gains? Are their fitness effects environment specific, or are they broadly beneficial across a range of environments? To answer these questions, we used two subsets (n = 18 and n = 63) of a large library of mutants carrying antibiotic resistance mutations in the bacterium Pseudomonas fluorescens whose fitness, along with the antibiotic sensitive ancestor, was assayed across 95 novel environments differing in the carbon source available for growth. We explore patterns of genotype-by-environment (G×E) interactions and ecological specialization among the 18 mutants initially found superior to the sensitive ancestor in one environment. We find that G×E is remarkably similar between the two sets of mutants and that beneficial mutants are not typically associated with large costs of adaptation. Fitness effects among beneficial mutants depart from a strict exponential distribution: they assume a variety of shapes that are often roughly L shaped but always right truncated. Distributions of (beneficial) fitness effects predicted by a landscape model assuming multiple traits underlying fitness and a single optimum often provide a good description of the empirical distributions in our data. Simulations of data sets containing a mixture of single and double mutants under this landscape show that inferences about the distribution of fitness effects of beneficial mutants is quite robust to contamination by second-site mutations.
Complex Mechanisms Regulate Developmental Expression of thematA(HMG) Mating Type Gene in HomothallicAspergillus nidulans
Authors: Czaja Wioletta , Miller Karen Y , Miller Bruce L
Published: August 2011

Sexual reproduction is a fundamental developmental process that allows for genetic diversity through the control of zygote formation, recombination, and gametogenesis. The correct regulation of these events is paramount. Sexual reproduction in filamentous fungi, including mating strategy (self-fertilization/homothallism or outcrossing/heterothallism), is determined by the expression of mating type genes at mat loci. Aspergillus nidulans matA encodes a critical regulator that is a fungal ortholog of the hSRY/SOX9 HMG box proteins. In contrast to well-studied outcrossing systems, the molecular basis of homothallism and role of mating type genes during a self-fertile sexual cycle remain largely unknown. In this study the genetic model organism, A. nidulans, has been used to investigate the regulation and molecular functions of the matA mating type gene in a homothallic system. Our data demonstrate that complex regulatory mechanisms underlie functional matA expression during self-fertilization and sexual reproduction in A. nidulans. matA expression is suppressed in vegetative hyphae and is progressively derepressed during the sexual cycle. Elevated levels of matA transcript are required for differentiation of fruiting bodies, karyogamy, meiosis, and efficient formation of meiotic progeny. matA expression is driven from both initiator (Inr) and novel promoter elements that are tightly developmentally regulated by position-dependent and position-independent mechanisms. Deletion of an upstream silencing element, matA SE, results in derepressed expression from wild-type (wt) promoter elements and activation of an additional promoter. These studies provide novel insights into the molecular basis of homothallism in fungi and genetic regulation of sexual reproduction in eukaryotes.
Hybrid Male Sterility in Rice Is Due to Epistatic Interactions with a Pollen Killer Locus
Authors: Kubo Takahiko , Yoshimura Atsushi , Kurata Nori
Published: August 2011

In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica and japonica, the hybrid male sterility gene S24 causes the selective abortion of male gametes carrying the japonica allele (S24-j) via an allelic interaction in the heterozygous hybrids. In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F1) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC2F1 population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic  Factor for  S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can dominantly counteract the pollen sterility caused by S24 heterozygosity. In summary, our results demonstrate that an additional epistatic locus is an essential element in the hybrid sterility caused by allelic interaction at a single locus in rice. This finding provides a significant contribution to our understanding of the complex molecular mechanisms underlying hybrid sterility and microsporogenesis.
Cell Architecture: Surrounding Muscle Cells Shape Gland Cell Morphology in the Caenorhabditis elegans Pharynx
Authors: Raharjo Wahyu Hendrati , Ghai Vikas , Dineen Aidan , Bastiani Michael , Gaudet Jeb
Published: August 2011

The acquisition and maintenance of shape is critical for the normal function of most cells. Here we investigate the morphology of the pharyngeal glands of Caenorhabditis elegans. These unicellular glands have long cellular processes that extend discrete lengths through the pharyngeal musculature and terminate at ducts connected to the pharyngeal lumen. From a genetic screen we identified several mutants that affect pharyngeal gland morphology. The most severe such mutant is an allele of sma-1, which encodes a β-spectrin required for embryonic elongation, including elongation of the pharynx. In sma-1 mutants, gland projections form normally but become increasingly abnormal over time, acquiring additional branches, outgrowths, and swelling, suggestive of hypertrophy. Rather than acting in pharyngeal glands, sma-1 functions in the surrounding musculature, suggesting that pharyngeal muscles play a critical role in maintenance of gland morphology by restricting their growth, and analysis of other mutants known to affect pharyngeal muscles supports this hypothesis. We suggest that gland morphology is maintained by a balance of forces from the muscles and the glands.