bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate defamation: reputation, rights and remedies
Authors: Chan Gary KY
Published: November 2012

This paper examines fundamental issues concerning a corporation's right to sue for defamatory attacks on its reputation, the scope of the right and the remedies available. It first outlines the opposed positions in England and Australia, respectively. It also argues that a corporation, save for a government corporation that exercises governmental functions based on markedly different rationales, should have the right to sue in defamation premised on the concept of corporate reputation as property and for the purpose of vindicating its reputation. On the question of remedies, a corporation should be entitled to recover special damages as reparation for damage to reputation provided they are proved. This paper considers, instead of presumed damages, alternative remedies for vindicating corporate reputation. Finally, it examines the business and non-business reputations of both trading and non-trading corporations in relation to claims for damages.
Typical and atypical dermoscopic presentations of dermatofibroma
Authors: Ferrari A. , Argenziano G. , Buccini P. , Cota C. , Sperduti I. , De Simone P. , Eibenschutz L. , Silipo V. , Zalaudek I. , Catricalà C.
Published: November 2012

Background  Dermatofibroma is a common skin neoplasm that is usually easy to recognize, but in some cases its differentiation from melanoma and other tumours may be difficult.

Objective  To describe the dermoscopic features of dermatofibromas, with special emphasis on the characteristics of atypical patterns, and to calculate pattern frequency according to the patients age and gender, anatomical site and histopathological subtype.

Methods  Two groups of patients were consecutively seen, one with dermatofibromas that were surgically excised because of clinically and/or dermoscopically equivocal aspects or following patient request, and another with non‐equivocal dermatofibromas. Each lesion was scored for previously reported global dermoscopic patterns and for additional features.

Results  A typical pattern was observed in 92 of 130 (70.8%) lesions, whereas an atypical pattern, that we named the ‘non Dermatofibroma (DF)‐like’ pattern, was seen in 38 of 130 (29.2%). Atypical dermatofibromas showed features reminiscent of different conditions, such as melanoma in 21(16.2%) cases, vascular tumour in six (4.6%), basal cell carcinoma in five (3.8%), collision tumour in three (2.3%) and psoriasis in three (2.3%). A significant association was found between the ‘melanoma‐like’ pattern/‘vascular tumour‐like’ pattern and males, whereas a trend was observed between the above‐mentioned patterns and hemosiderotic/aneurysmal DFs. ‘Peripheral pigment network and central white scar‐like patch’ pattern was found associated with females and classic histopathological variant of DF.

Conclusion  Dermatofibromas may display different morphological faces. The typical dermoscopic patterns allow a confident diagnosis, whereas a full surgical excision is always recommended in all doubtful cases.
Morphological and Molecular Description of Three New Species of the Cyrtophorid Genus Chlamydodon (Ciliophora, Cyrtophoria)
Authors: Pan Hongbo , Li Lifang , Al‐Rasheid Khaled A.S. , Song Weibo
Published: November 2012

This study investigates the morphology and molecular characteristics of three new cyrtophorid ciliates isolated from China seas: Chlamydodon salinus n. sp., Chlamydodon caudatus n. sp., and Chlamydodon paramnemosyne n. sp. Of these, C. salinus n. sp. differs from its congeners through a combination of body size, a cross‐striated band that is not continuous, the presence of 30–34 somatic kineties, 11–15 nematodesmal rods, and 13 contractile vacuoles. Chlamydodon caudatus n. sp., meanwhile, is characterized by having a conspicuous tail, a continuous cross‐striated band, 34–40 somatic kineties, about 15 contractile vacuoles, and 20–24 nematodesmal rods. Compared with other Chlamydodon species, the third new one, C. paramnemosyne n. sp., could be identified by its continuous cross‐striated band, 16–18 somatic kineties, 5 contractile vacuoles, and 9–12 nematodesmal rods. Based on the sequence of the small subunit (SSU) rRNA gene, the phylogeny of these three new species was analyzed, indicating that they all clustered with other congeners to form a monophyletic assemblage. Based on previous studies and the present work, a brief revision of the genus Chlamydodon is supplied, and a key to aid the identification of Chlamydodon species is given.
Performance of double‐balloon enteroscopy for the management of small bowel polyps in hamartomatous polyposis syndromes
Authors: Gorospe Emmanuel C , Alexander Jeffrey A , Bruining David H , Rajan Elizabeth , Wong Kee Song Louis‐Michel
Published: November 2012

Background and Aim

Hamartomatous polyposis syndromes (HPS) are a group of rare inherited autosomal dominant disorders. Small bowel polyposis is one of the manifestations of HPS. Double‐balloon enteroscopy (DBE) with polypectomy may obviate repeated small bowel surgeries for polyp intussusception, obstruction, or bleeding. The efficacy and safety of DBE‐assisted polypectomy in HPS patients with clinically significant small bowel polyposis were evaluated.

Methods

All HPS patients who underwent DBE from January 2007 to April 2011 were identified using a prospectively maintained database. Data on patient demographics, pre‐DBE radiological studies, polyp characteristics, procedural outcomes, and complications were abstracted.

Results

Twenty‐two patients underwent a total of 34 DBE procedures. Pre‐DBE imaging included computed tomography enterography (n = 15), computed tomography enteroclysis (n = 5), small bowel follow‐through (n = 1), and magnetic resonance enterography (n = 1). Any small bowel polyp ≥ 1 cm in size on radiological imaging was referred for DBE‐assisted polypectomy. Antegrade and retrograde DBE were successful in reaching and resecting targeted polyps in 90% (18/20) and 71.4% (10/14) of procedures, respectively. The overall success rate for DBE‐assisted polypectomy was 82.3% (95% confidence interval: 66.5–91.6%). The median size of resected polyps was 2 cm (range 1–5 cm) and all were hamartomas. Minor adverse events occurred in four (11.8%) procedures, including abdominal pain (n = 2), immediate post‐polypectomy bleeding (n = 1), and self‐limited hematochezia (n = 1).

Conclusions

DBE‐assisted polypectomy was successful in over 80% of HPS patients with an acceptable margin of safety. To the knowledge of the authors, this is one of the largest single‐center studies to report on the performance and safety of DBE‐assisted polypectomy in HPS patients.
Histological features responsible for brownish epithelium in squamous neoplasia of the esophagus by narrow band imaging
Authors: Kanzaki Hiromitsu , Ishihara Ryu , Ishiguro Shingo , Nagai Kengo , Matsui Fumi , Yamashina Takeshi , Ohta Takashi , Yamamoto Sachiko , Hanaoka Noboru , Hanafusa Masao , Takeuchi Yoji , Higashino Koji , Uedo Noriya , Iishi Hiroyasu , Tomita Yasuhiko
Published: November 2012

Background and Aim

Esophageal squamous neoplasias usually appear brown under narrow band imaging as a result of microvascular proliferation, and brownish color changes in the areas between vessels, referred to as brownish epithelium. However, the reasons for the development of this brownish epithelium and its clinical implications have not been fully investigated.

Methods

Patients with superficial esophageal neoplasias treated by endoscopic resection were included in the study. Areas of mucosa with brownish and non‐brownish epithelia were evaluated histologically.

Results

A total of 68 superficial esophageal neoplasias in 58 patients were included in the analysis. Of the 68 lesions, 32 were classified in the brownish epithelium group, and 36 in the non‐brownish epithelium group. Brownish epithelium was significantly associated with a diagnosis of high‐grade intraepithelial neoplasia or invasive cancer (P < 0.0001). Thinning of the keratinous layer, thinning of the epithelium, and cellular atypia were significantly associated with brownish epithelium by univariate analysis, and thinning of the keratinous layer and thinning of the epithelium were confirmed to be independent factors by multivariate analysis. The odds ratios were 9.6 (95% confidence interval: 2.0–46.3) for thinning of the keratinous layer, and 4.6 (95% confidence interval: 1.1–19.4) for thinning of the epithelium.

Conclusions

Brownish epithelium is an important finding in the diagnosis of esophageal squamous neoplasia, and may be related to thinning of the keratinous layer, caused by neoplastic cell proliferation, and thinning of the epithelium.
Sex, ethnicity, and slow acetylator profile are the major causes of hepatotoxicity induced by antituberculosis drugs
Authors: Chamorro Julián G , Castagnino Jorge P , Musella Rosa M , Nogueras Mabel , Aranda Federico M , Frías Ana , Visca Mabel , Aidar Omar , Perés Silvia , de Larrañaga Gabriela F
Published: November 2012

Background and Aim

Treatment with antituberculosis (TB) drugs produces liver damage in a large proportion of patients. Isoniazid, an antibacterial drug, is primarily responsible for this hepatotoxicity. Several polymorphisms of the N‐acetyltransferase 2 (NAT‐2) and cytochrome P450 2E1 enzymes, which are involved in the metabolism of isoniazid, may be directly associated with the development of hepatotoxicity. This study was designed to analyze the association between the NAT‐2 and CYP2E1 polymorphisms with the development of anti‐TB drug‐induced hepatotoxicity (ATDH).

Methods

One hundred and seventy‐five TB patients who had been treated with anti‐TB drugs were studied. The allelic and genotypic frequency distributions of the NAT‐2 and CYP2E1 enzymes were studied using polymerase chain reaction–restriction fragment length polymorphisms methodology. A binary logistic regression analysis was used to compare the results between TB patients with and without the development of hepatotoxicity.

Results

Having a slow acetylator status (odds ratio [OR] = 2.615; confidence interval [CI] = 1.264–5.411; P = 0.01), being female (OR = 2.734; CI = 1.325–5.639, P = 0.006), and having Bolivian ethnicity (OR = 2.711; CI = 1.307–6.625, P = 0.007) were found to be independent predictor variables for ATDH.

Conclusions

This study showed that a patient's NAT‐2 acetylator status, gender, and ethnic origin may be regarded as important risk factors for developing hepatotoxicity. Contrary to expectations, the CYP2E1 c1/c2 polymorphism did not show a significant association with hepatotoxicity in this study. Given the increases in TB cases and ATDH incidence levels, as well as the associated hospitalization costs, it may also be helpful to know patients’ acetylator status prior to or at the beginning of the TB treatment regimen.
Studying Circular Questioning “In Situ”: Discourse Analysis of A First Systemic Family Therapy Session
Authors: Diorinou Maria , Tseliou Eleftheria
Published: November 2012

The present article focuses on the study of circular questioning “in situ,” that is, in the context of the discursive arena of an actual first systemic family therapy session. Two typical circular questions are selected, and discourse analysis heavily drawing from the discursive action model is deployed with the aim to highlight their function in the context of therapist and family members' problem talk. The analysis demonstrates the gradual building of two respective patterns, which both exhibit signs of shifts toward the instillment of a systemic epistemology in relation to problem talk: a shift from homogeneity to heterogeneity in family members' voices, which legitimizes the existence of different viewpoints within a system, and a shift from the construction of an accusation toward its deconstruction, which challenges the linear perception of causality underlying the accusation, thus introducing a more circular perspective. Implications are discussed in relation to contemporary, constructionist systemic family therapy practice, and reference is made to the methodological “promises” and challenges of the deployment of discourse analysis for the scrutiny of systemic family therapy therapeutic techniques and tools under a discursively informed light.
The Genus Cladophora Kützing (Ulvophyceae) as a Globally Distributed Ecological Engineer
Authors: Zulkifly Shahrizim B. , Graham James M. , Young Erica B. , Mayer Robert J. , Piotrowski Michael J. , Smith Izak , Graham Linda E.
Published: November 2012

The green algal genus Cladophora forms conspicuous nearshore populations in marine and freshwaters worldwide, commonly dominating peri‐phyton communities. As the result of human activities, including the nutrient pollution of nearshore waters, Cladophora‐dominated periphyton can form nuisance blooms. On the other hand, Cladophora has ecological functions that are beneficial, but less well appreciated. For example, Cladophora has previously been characterized as an ecological engineer because its complex structure fosters functional and taxonomic diversity of benthic microfauna. Here, we review classic and recent literature concerning taxonomy, cell biology, morphology, reproductive biology, and ecology of the genus Cladophora, to examine how this alga functions to modify habitats and influence littoral biogeochemistry. We review the evidence that Cladophora supports large, diverse populations of microalgal and bacterial epiphytes that influence the cycling of carbon and other key elements, and that the high production of cellulose and hydrocarbons by Cladophora‐dominated periphyton has the potential for diverse technological applications, including wastewater remediation coupled to renewable biofuel production. We postulate that well‐known aspects of Cladophora morphology, hydrodynamically stable and perennial holdfasts, distinctively branched architecture, unusually large cell and sporangial size and robust cell wall construction, are major factors contributing to the multiple roles of this organism as an ecological engineer.
Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC)
Authors: Park Joong‐Won , Amarapurkar Deepak , Chao Yee , Chen Pei‐Jer , Geschwind Jean‐Francois H. , Goh Khean Lee , Han Kwang‐Hyub , Kudo Masatoshi , Lee Han Chu , Lee Rheun‐Chuan , Lesmana Laurentius A. , Lim Ho Yeong , Paik Seung Woon , Poon Ronnie T , Tan Chee‐Kiat , Tanwandee Tawesak , Teng Gaojun , Cheng Ann‐Lii
Published: November 2012

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate‐stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non‐response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long‐term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.
Identifying biases at different spatial and temporal scales of diversification: a case study in the Neotropical parrotlet genus Forpus
Authors: Smith Brian Tilston , Ribas Camila C. , Whitney Bret M. , HernÁndez‐baÑos Blanca E. , Klicka John
Published: November 2012

The temporal origins of the extraordinary biodiversity of the Neotropical region are highly debated. Recent empirical work has found support for alternative models on the tempo of speciation in Neotropical species further fuelling the debate. However, relationships within many Neotropical lineages are poorly understood, and it is unclear how this uncertainty impacts inferences on the evolution of taxa in the region. We examined the robustness of diversification patterns in the avian genus Forpus by testing whether the use of different units of biodiversity (i.e. biological species and statistically inferred species) impacted diversification rates and inferences regarding important biogeographic breaks in the genus. We found that the best‐fit model of diversification for the biological species data set was a declining rate of diversification; whereas a model of constant diversification was the best‐fit model for statistically inferred species or subspecies. Moreover, the relative importance of different landscape features in delimiting genetic structure across the landscape varied across data sets with differing units of biodiversity. Patterns based on divergence times among biological species indicated old speciation events across major geographic and river barriers. In contrast, data sets more inclusive of the diversity in Forpus illustrate the role of both old divergence across major landscape features and more recent divergences that are possibly attributed to Pleistocene climatic changes. Overall, these results indicate that conflicting models on the temporal origins of Neotropical birds may be attributable to sampling biases.
Amplicon‐pyrosequencing‐based detection of compositional shifts in bryophyte‐associated fungal communities along an elevation gradient
Authors: Davey Marie L. , Heegaard Einar , Halvorsen Rune , Kauserud Håvard , Ohlson Mikael
Published: November 2012

Although bryophytes are a dominant vegetation component of boreal and alpine ecosystems, little is known about their associated fungal communities. HPLC assays of ergosterol (fungal biomass) and amplicon pyrosequencing of the ITS2 region of rDNA were used to investigate how the fungal communities associated with four bryophyte species changed across an elevational gradient transitioning from conifer forest to the low‐alpine. Fungal biomass and OTU richness associated with the four moss hosts did not vary significantly across the gradient (P > 0.05), and both were more strongly affected by host and tissue type. Despite largely constant levels of fungal biomass, distinct shifts in community composition of fungi associated with Hylocomium, Pleurozium and Polytrichum occurred between the elevation zones of the gradient. This likely is a result of influence on fungal communities by major environmental factors such as temperature, directly or indirectly mediated by, or interacting with, the response of other components of the vegetation (i.e. the dominant trees). Fungal communities associated with Dicranum were an exception, exhibiting spatial autocorrelation between plots, and no significant structuring by elevation. Nevertheless, the detection of distinct fungal assemblages associated with a single host growing in different elevation zones along an elevational gradient is of particular relevance in the light of the ongoing changes in vegetation patterns in boreal and alpine systems due to global climate warming.
Asymmetric hybridization and gene flow between Joshua trees (Agavaceae: Yucca) reflect differences in pollinator host specificity
Authors: Starr Tyler N. , Gadek Katherine E. , Yoder Jeremy B. , Flatz Ramona , Smith Christopher I.
Published: November 2012

The angiosperms are by far the largest group of terrestrial plants. Their spectacular diversity is often attributed to specialized pollination. Obligate pollination mutualisms where both a plant and its pollinator are dependent upon one another for reproduction are thought to be prone to rapid diversification through co‐evolution and pollinator isolation. However, few studies have evaluated the degree to which pollinators actually mediate reproductive isolation in these systems. Here, we examine evidence for hybridization and gene flow between two subspecies of Joshua tree (Yucca brevifolia brevifolia and Yucca brevifolia jaegeriana) pollinated by two sister species of yucca moth. Previous work indicated that the pollinators differ in host specificity, and DNA sequence data suggested asymmetric introgression between the tree subspecies. Through intensive sampling in a zone of sympatry, a large number of morphologically intermediate trees were identified. These included trees with floral characters typical of Y. b. jaegeriana, but vegetative features typical of Y. b. brevifolia. The opposite combination—Y. b. brevifolia flowers with Y. b. jaegeriana vegetative morphology—never occurred. Microsatellite genotyping revealed a high frequency of genetically admixed, hybrid trees. Coalescent‐based estimates of migration indicated significant gene flow between the subspecies and that the direction of gene flow matches differences in pollinator host fidelity. The data suggest that pollinator behaviour determines the magnitude and direction of gene flow between the two subspecies, but that specialized pollination alone is not sufficient to maintain species boundaries. Natural selection may be required to maintain phenotypic differences in the face of ongoing gene flow.
Nus transcription elongation factors and RNase III modulate small ribosome subunit biogenesis in Escherichia coli
Authors: Bubunenko Mikhail , Court Donald L. , Al Refaii Abdalla , Saxena Shivalika , Korepanov Alexey , Friedman David I. , Gottesman Max E. , Alix Jean‐Hervé
Published: November 2012

Escherichia coli NusA and NusB proteins bind specific sites, such as those in the leader and spacer sequences that flank the 16S region of the ribosomal RNA transcript, forming a complex with RNA polymerase that suppresses Rho‐dependent transcription termination. Although antitermination has long been the accepted role for Nus factors in rRNA synthesis, we propose that another major role for the Nus‐modified transcription complex in rrn operons is as an RNA chaperone insuring co‐ordination of 16S rRNA folding and RNase III processing that results in production of proper 30S ribosome subunits. This contrarian proposal is based on our studies of nusA and nusB cold‐sensitive mutations that have altered translation and at low temperature accumulate 30S subunit precursors. Both phenotypes are suppressed by deletion of RNase III. We argue that these results are consistent with the idea that the nus mutations cause altered rRNA folding that leads to abnormal 30S subunits and slow translation. According to this idea, functional Nus proteins stabilize an RNA loop between their binding sites in the 5′ RNA leader and on the transcribing RNA polymerase, providing a topological constraint on the RNA that aids normal rRNA folding and processing.
Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls
Authors: Loots C. , Smits M. , OMARI T. , Bennink R. , Benninga M. , VAN WIJK M.
Published: November 2012

Background  Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying.

Methods  Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and 13C‐octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min.

Key Results  Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4–14) and 4.5 (2–6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2–4) and 4 (3–6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak 13CO2 excretion faster and proximal gastric distension was more pronounced.

Conclusions & Inferences  In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC.
miR‐370 modulates insulin receptor substrate‐1 expression and inhibits the tumor phenotypes of oral carcinoma
Authors: Chang K‐W , Chu T‐H , Gong N‐R , Chiang W‐F , Yang C‐C , Liu C‐J , Wu C‐H , Lin S‐C
Published: November 2012

Background

MicroRNAs play important roles in carcinogenesis. A preliminary screening study suggested that down‐regulation of miR‐370 occurs in oral squamous cell carcinoma (OSCC) tissue. Insulin receptor substratre‐1 (IRS‐1) is the substrate of insulin‐like growth factor receptor (IGFR), which modulates AKT/mTOR activation in malignancies. The relationship between miR‐370 and IRS‐1, and their functional roles in OSCC pathogenesis are unclear.

Materials and Methods

Primary OSCC specimens were examined for miR‐370 expression. Exogenous expression of miR‐370 was established using both stable subclones and transient expression, and these were used to gain insights into miR‐370's functions in OSCC cells. Knockdown of miR‐370 and IRS‐1 was also carried out in OSCC cells using a small interference oligonucleotide approach.

Results

Squamous cell carcinoma tissues with perineural invasion had lowered miR‐370 expression compared with contrasting OSCC. OSCC cells also exhibited lower miR‐370 expression than normal oral keratinocytes, and this can be reversed by treatment with 5‐aza‐2′‐deoxycytidine. Exogenous miR‐370 expression decreases the migration and anchorage‐independent growth of OSCC cells, which implies a suppressor role for miR‐370. The enhancement of anchorage‐independent growth of OSCC cells through miR‐370 inhibiting can be reduced by knockdown of IRS‐1 expression.

Conclusion

This study concludes that miR‐370 is able to target IRS‐1 for oral tumorigenesis.
Non‐Linear Pricing and Price Indexes: Evidence and Implications from Scanner Data
Authors: Fox Kevin J. , Melser Daniel
Published: November 2012

Non‐linear pricing, the fact that prices do not necessarily change in proportion to size, is a ubiquitous phenomenon. However, it has been neither particularly well understood nor well measured. Non‐linear pricing is of practical importance for statistical agencies who, in constructing price indexes, are often required to compare the relative price of a product‐variety of two different sizes. It is usually assumed that prices change one‐for‐one with package and pack size (e.g. a 1‐liter cola costs half as much as a 2‐liter bottle). We question the wisdom of such an assumption and outline a model to flexibly estimate the price‐size function. Applying our model to a large U.S. scanner dataset for carbonated beverages, at a disaggregated level, we find very significant discounts for larger‐sized products. This highlights the need to pursue methods such as those advocated in this paper.
Socioeconomic burden of lymphatic filariasis in Georgetown, Guyana
Authors: Tyrell Ede
Published: November 2012

Objective

To assess the socioeconomic impact of lymphatic filariasis (LF) in Guyana.

Methods

Observational, cross‐sectional study of 50 persons with chronic LF attending the Filariasis Clinic who were selected as the cases; and 50 persons with chronic skin conditions but no chronic LF, attending the Skin Clinic who were selected as the controls. The two groups were assessed using semi‐structured interviews.

Results

Socioeconomic impact was statistically significant, especially with respect to ‘having to change jobs’ and experiencing major emotional and financial changes (P < 0.05). Fifty‐six per cent of cases reported a major change since their diagnosis, whereas only 32% of controls did. Cases were less likely to be able to dress themselves and walk inside and outside the house than controls; they were three times more likely to spend money on transportation than controls (OR, 3.04 95% CI 1.11, 8.44).

Conclusion

Patients with chronic LF face a considerable burden, which should be addressed as part of the Elimination Programme. One way in which this can be done is to provide free transportation for patients with chronic LF to and from Filariasis Clinics.
Interleukin‐1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse
Authors: Toldo Stefano , Mezzaroma Eleonora , Van Tassell Benjamin W. , Farkas Daniela , Marchetti Carlo , Voelkel Norbert F. , Abbate Antonio
Published: November 2012

New Findings

What is the central question of this study?

The formation of the cryopyrin inflammasome in the heart induces an intense inflammatory response during acute myocardial infarction, which mediates further damage and promotes adverse cardiac remodelling. The present study investigates the role of interleukin‐1β in mediating the pathological effects of the inflammasome in the heart.

What is the main finding and its importance?

Blockade of interleukin‐1β improves cardiac remodelling after acute myocardial infarction in the mouse by inhibiting apoptosis without affecting the formation or the activity of the inflammasome in the heart. These findings suggest that interleukin‐1β mediates the deleterious effects on the heart during the sterile inflammatory response.

The formation of the cryopyrin inflammasome in the heart induces an intense inflammatory response during acute myocardial infarction (AMI), which mediates further damage and promotes adverse cardiac remodelling. Active interleukin‐1β (IL‐1β) is a key product of the inflammasome, being cleaved by active caspase‐1. The aim of this study was to dissect the role of IL‐1β from that of the inflammasome by using a neutralizing monoclonal antibody directed against IL‐1β and measuring the intensity of the inflammatory response, the activity of caspase‐1 in the inflammasome, cardiomyocyte apoptosis and cardiac remodelling in a mouse model of non‐reperfused AMI. A mouse monoclonal IgG2a antibody directed against IL‐1β (IL‐1β‐AB; 10 mg kg−1) was given i.p. immediately after surgery and repeated 1 week later. Cardiac tissue was analysed at 72 h after surgery in a subgroup of mice for inflammasome aggregates and caspase‐1 activity (inflammasome) and for DNA fragmentation and caspase‐3 activity (apoptosis). All sham‐operated mice were alive at 10 weeks, whereas 40% of the control‐antibody‐treated mice and 30% of the IL‐1β‐AB‐treated mice died during the 4 weeks after surgery. When compared with vehicle, treatment with the IL‐1β‐AB did not affect inflammasome formation or caspase‐1 activation in the heart tissue at 72 h after AMI nor circulating plasma IL‐6 levels, but did inhibit cardiomyocyte apoptosis, limit left ventricular enlargement by 40% (P < 0.01) and improve systolic dysfunction by 17% (P < 0.01) after AMI. These findings suggest that IL‐1β mediates the deleterious effects on the heart during the sterile inflammatory response.
Increasing brain serotonin corrects CO2 chemosensitivity in methyl‐CpG‐binding protein 2 (Mecp2)‐deficient mice
Authors: Toward Marie A. , Abdala Ana P. , Knopp Sharon J. , Paton Julian F. R. , Bissonnette John M.
Published: November 2012

New Findings

What is the central question of this study?

Mice deficient in methyl‐CpG‐binding protein 2 (Mecp2; a model of Rett syndrome) display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. Patients and mice show reduced levels of brain 5‐HT, which is important in central chemosensitivity. It is not known whether increasing 5‐HT in this mouse model would improve their respiratory response to CO2.

What is the main finding and its importance?

We show, for the first time, that females heterozygous for the Mecp2 mutation have a higher hypocapnic threshold for apnoeas versus wild‐type mice and that increasing 5‐HT in Mecp2‐null males, with citalopram, can correct CO2 chemosensitivity, a finding that may be important clinically.

Mice deficient in the transcription factor methyl‐CpG‐binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for Mecp2 show reduced levels of brain serotonin (5‐HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5‐HT in this mouse model would improve their respiratory response to CO2. Here we determined the apnoeic threshold in heterozygous Mecp2‐deficient female mice and examined the effects of blocking 5‐HT reuptake on the CO2 response in Mecp2‐null male mice. Studies were performed in B6.129P2(C)‐Mecp2τm1.1Bird null males and heterozygous females. In an in situ preparation, seven of eight Mecp2‐deficient heterozygous females showed arrest of phrenic nerve activity when arterial CO2 was lowered to 3%, whereas the wild‐types maintained phrenic nerve amplitude at 53 ± 3% of maximal. In vivo plethysmography studies were used to determine CO2 chemosensitivity in null males. These mice were exposed sequentially to 1, 3 and 5% CO2. The percentage increase in minute ventilation in response to increased inspired CO2 was less in Mecp2−/y than in Mecp2+/y mice. Pretreatment with citalopram, a selective 5‐HT reuptake inhibitor (2.5 mg kg−1 i.p.), 40 min prior to CO2 exposure, in Mecp2−/y mice resulted in an improvement in CO2 chemosensitivity to wild‐type levels. These results suggest that decreased 5‐HT in Mecp2‐deficient mice reduces CO2 chemosensitivity, and restoring 5‐HT levels can reverse this effect.
Similar skeletal muscle angiogenic and mitochondrial signalling following 8 weeks of endurance exercise in mice: discontinuous versus continuous training
Authors: Malek Moh H. , Hüttemann Maik , Lee Icksoo , Coburn Jared W.
Published: November 2012

New Findings

What is the central question of this study?

Little is known about skeletal muscle adaptation to discontinuous endurance training. Despite little research, it has been suggested that accumulating 30 min of endurance exercise daily may result in similar adaptations in the working muscle to a 30 min exercise bout.

What is the main finding and its importance?

The unique finding of the present investigation was that 10 min of continuous endurance training performed three times daily results in similar adaptations of the angiogenic and mitochondrial signalling pathways to 30 min of continuous exercise. Taken together, these adaptations in the working muscle improved exercise tolerance.

Little is known about skeletal muscle adaptation to discontinuous endurance training. It has been suggested that accumulating 30 min of endurance exercise daily may result in similar adaptations in the working muscle to a 30 min exercise bout. The purposes of the present investigation, therefore, were to conduct an 8 week continuous or discontinuous endurance training regimen and determine the following: (i) whether treadmill exercise capacity differs between the two training regimens; and (ii) whether the angiogenic and mitochondrial signalling pathways are differentially activated in the two training regimens. Twenty‐four young adult male FVB/NJ mice were randomized into the following three groups: control; continuous treadmill endurance training for 30 min five times a week; or discontinuous treadmill endurance training for a total of 30 min five times per week for three 10 min intervals with 2 h rest between intervals. After the intervention, endurance capacity increased by 60% (P < 0.001) in both exercise groups compared to control animals. For the quadriceps muscle, anti‐angiogenic regulators (thrombospondin‐1 and ADAMTS1) were reduced by 50–70% (P < 0.001) with either exercise regimen. In addition, phosphorylation of p38 mitogen‐activated protein kinase signalling increased by 50–300% (P < 0.001), which corresponded to an increase in peroxisome proliferator‐activated receptor γ coactivator 1 β (PGC‐1β) protein expression. These findings suggest that accumulating 30 min of endurance exercise in 10 min sessions results in similar endurance training adaptations in skeletal muscle to a 30 min exercise bout.
Flow-Induced Deformation of Poroelastic Tissues and Gels: A New Perspective on Equilibrium Pressure-Flow-Thickness Relations
Authors: Quinn Thomas M.
Published: November 2012

Hydrostatic pressure-driven flows through soft tissues and gels cause deformations of the solid network to occur, due to drag from the flowing fluid. This phenomenon occurs in many contexts including physiological flows and infusions through soft tissues, in mechanically stimulated engineered tissues, and in direct permeation measurements of hydraulic permeability. Existing theoretical descriptions are satisfactory in particular cases, but none provide a description which is easy to generalize for the design and interpretation of permeation experiments involving a range of different boundary conditions and gel properties. Here a theoretical description of flow-induced permeation is developed using a relatively simple approximate constitutive law for strain-dependent permeability and an assumed constant elastic modulus, using dimensionless parameters which emerge naturally. Analytical solutions are obtained for relationships between fundamental variables, such as flow rate and pressure drop, which were not previously available. Guidelines are provided for assuring that direct measurements of hydraulic permeability are performed accurately, and suggestions emerge for alternative measurement protocols. Insights obtained may be applied to interpretation of flow-induced deformation and related phenomena in many contexts.
Atomic layer deposition of zinc indium sulfide films: Mechanistic studies and evidence of surface exchange reactions and diffusion processes
Authors: Genevée Pascal , Donsanti Frédérique , Schneider Nathanaelle , Lincot Daniel
Published: November 2012

The authors present the elaboration of zinc indium sulfide (ZnInxSy) thin films in the context of a cadmium-free buffer layer development for copper indium gallium diselenide photovoltaic solar cells. The films were deposited by atomic layer deposition (ALD) from ZnEt2 (DEZ), In(acac)3 (acac = acetylacetonate), and H2S at 200 °C. In situ growth kinetics studies were performed with the quartz crystal microbalance technique to determine the respective mass gain per cycle of ZnS and In2S3 layers, allowing determination of the atomic compositions of the ZnInxSy thin films to be expected if the deposition strictly follows the rule of mixtures. As the experimental atomic compositions of the ZnInxSy films differ significantly from this rule, a comprehensive study of the growth mechanism was performed to determine the nature of the side reactions. First, an exchange reaction between In2S3 and the Zn precursor was identified, though this process is not sufficient to account for the experimental data, and therefore, a second process which corresponds to the diffusion of species within the film was also found to take place. Ultimately, the atomic compositions of the ZnInxSy films can be explained by a rate-limited exchange reaction at the surface between DEZ and the In2S3 layer, combined with diffusion of the species in the whole film. More generally, such side reactions should be considered in ALD of multinary compounds, even at low temperature.
Magnetically coupled ultrahigh vacuum manipulator with a sample grabber
Authors: Heon Kim Seong , de Lozanne Alex
Published: November 2012

The authors present a simple design for a magnetically coupled manipulator capable of grabbing small samples in an ultrahigh vacuum environment. The opening and closing of the sample grabber is accomplished by the relative rotation of independent rings of magnets. This manipulator provides high values of axial force (30 lb) and azimuthal torque (23 in. lb).
Experimental determination of the Boltzmann constant: An undergraduate laboratory exercise for molecular physics or physical chemistry
Authors: Campbell H. M. , Boardman B. M. , DeVore T. C. , Havey D. K.
Published: November 2012

This article describes an undergraduate laboratory exercise that uses optical spectroscopy to determine the magnitude and the uncertainty of the Boltzmann constant kb. The more accurate approach uses photoacoustic spectroscopy to measure the Doppler-broadened line profile of individual spectral lines of N2O to extract kb. Measurements and estimates of the uncertainties in the quantities needed to calculate kb from the line profiles are then used to estimate the uncertainty in kb. This experiment is unusual in that it uses advanced laser-based spectroscopy techniques to emphasize standard practices of uncertainty analysis. The core instrumentation is modular and relatively affordable; it requires a tunable single-mode laser, photoreceiver, optical cell, and vacuum pump. If this instrumentation is not available, an alternate approach can be performed which uses the intensity of each rotational transition of an infrared band to measure kb. Although there is more uncertainty using the alternate approach, low concentrations of CO2, DCl, or N2O give reasonable results for the magnitude of kb. Student assessment results indicate retention and mastery of the concept of combined measurement uncertainty.
The Structure of Native Influenza Virion Ribonucleoproteins
Authors: Arranz Rocío , Coloma Rocío , Chichón Francisco Javier , Conesa José Javier , Carrascosa José L. , Valpuesta José M. , Ortín Juan , Martín-Benito Jaime
Published: November 2012

Influenza Revealed

Influenza virus, a single-stranded RNA virus, is responsible for substantial morbidity and mortality worldwide. The influenza ribonucleoprotein (RNP) complex, which carries out viral replication and transcription, is central to the virus life-cycle and to viral host adaptation (see the Perspective by

Tao and Zheng

). Structural characterization of the viral RNP has been challenging, but

Moeller
et al.

(p.
1631
, published online 22 November) and

Arranz
et al.

(p.
1634
, published online 22 November) now report the structure and assembly of this complex, using cryo-electron microscopy and negative-stain electron microscopy. The structures reveal how the viral polymerase, RNA genome, and nucleoprotein interact in the RNP providing insight into mechanisms for influenza genome replication and transcription.
Progenitor and Terminal Subsets of CD8
+
T Cells Cooperate to Contain Chronic Viral Infection
Authors: Paley Michael A. , Kroy Daniela C. , Odorizzi Pamela M. , Johnnidis Jonathan B. , Dolfi Douglas V. , Barnett Burton E. , Bikoff Elizabeth K. , Robertson Elizabeth J. , Lauer Georg M. , Reiner Steven L. , Wherry E. John
Published: November 2012

Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8
+
T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8
+
T cells during chronic viral infection. T-bet
hi
cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomes
hi
terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.
Visualizing the Influenza Genome
Authors: Tao Yitzhi Jane , Zheng Wenjie
Published: November 2012

The viral RNA in influenza virus forms helical hairpin structures in complex with several proteins.
E. Donnall Thomas (1920–2012)
Authors: Appelbaum Frederick R.
Published: November 2012

A physician's unrelenting commitment made bone marrow transplantation an effective cancer therapy.
Quality of descriptions of treatments: a review of published randomised controlled trials
Authors: Schroter Sara , Glasziou Paul , Heneghan Carl
Published: November 2012

Objectives

To be useable in clinical practise, treatments studied in trials must provide sufficient information to enable clinicians and researchers to replicate. We sought to assess the completeness of treatment descriptions in published randomised controlled trials (RCTs) using a checklist and to determine the extent to which peer reviewers and editors comment on the quality of reporting of treatments.

Design

A cross-sectional study.

Setting

Trials published in theBMJ, a general medical journal.

Participants

Fifty-one trials published in theBMJwere independently evaluated by two raters using a checklist. Reviewers’ and editors’ comments were also assessed for statements on treatment descriptions.

Primary and secondary outcome measures

Proportion of trials rated as replicable (primary outcome).

Results

For 57% (29/51) of the papers, published treatment descriptions were not considered sufficient to allow replication. Most poorly described aspects were the actual procedures involved including the sequencing of the technique (what happened and when) and the physical or informational materials used (eg, training materials): 53% and 43% not clear, respectively. For a third of treatments, the dose/duration of individual sessions was not clear and for a quarter the schedule (interval, frequency, duration or timing) was not clear. Although the majority of problems were not picked up by reviewers and editors, when they were detected only about two-thirds were fixed before publication.

Conclusions

Journals wanting to publish the research of use to practising healthcare professionals need to pay more attention to descriptions of treatments. Our checklist, may be useful for reviewers, and editors and could help ensure that important details of treatments are provided before papers are in the public domain.