Parallel evolution of facial stripe patterns in the Neolamprologus brichardilpulcher species complex endemic to Lake Tanganyika

Colour pattern diversity can be due to random processes or to natural or sexual selection. Consequently, similarities in colour patterns are not always correlated with common ancestry, but may result from convergent evolution under shared selection pressures or drift. Neolamprologus brichardi and Neolamprologus pulcher have been described as two distinct species based on differences in the arrangement of two dark bars on the operculum. Our study uses DNA sequences of the mitochondrial control region to show that relatedness of haplotypes disagrees with species assignment based on head colour pattern. This suggests repeated parallel evolution of particular stripe patterns. The complete lack of shared haplotypes between populations of the same or different phenotypes reflects strong philopatric behaviour, possibly induced by the cooperative breeding mode in which offspring remain in their natal territory and serve as helpers until they disperse to nearby territories or take over a breeding position. Concordant phylogeographic patterns between N. brichardi/N. pulcher populations and other rock-dwelling cichlids suggest that the same colonization routes have been taken by sympatric species and that these routes were affected by lake level fluctuations in the past. (C) 2007 Elsevier Inc. All rights reserved.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer

PURPOSE: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. Elucidating molecular pathways deregulated in ccRCC may point to novel prognostic parameters that facilitate planning of therapeutic approaches. EXPERIMENTAL DESIGN: Using tissue microarrays, expression patterns of 15 different proteins were evaluated in over 800 ccRCC patients to analyze pathways reported to be physiologically controlled by the tumor suppressors von Hippel-Lindau protein and phosphatase and tensin homologue (PTEN). Tumor staging and grading were improved by performing variable selection using Cox regression and a recursive bootstrap elimination scheme. RESULTS: Patients with pT2 and pT3 tumors that were p27 and CAIX positive had a better outcome than those with all remaining marker combinations. A prolonged survival among patients with intermediate grade (grade 2) correlated with both nuclear p27 and cytoplasmic PTEN expression, as well as with inactive, nonphosphorylated ribosomal protein S6. By applying graphical log-linear modeling for over 700 ccRCC for which the molecular parameters were available, only a weak conditional dependence existed between the expression of p27, PTEN, CAIX, and p-S6, suggesting that the dysregulation of several independent pathways are crucial for tumor progression. CONCLUSIONS: The use of recursive bootstrap elimination, as well as graphical log-linear modeling for comprehensive tissue microarray (TMA) data analysis allows the unraveling of complex molecular contexts and may improve predictive evaluations for patients with advanced renal cancer.

Longitudinal patterns in survival, comorbidity, healthcare utilization and quality of care among older women following breast cancer diagnosis

OBJECTIVES To compare longitudinal patterns of health care utilization and quality of care for other health conditions between breast cancer-surviving older women and a matched cohort without breast cancer. DESIGN Prospective five-year longitudinal comparison of cases and matched controls. SUBJECTS Newly identified breast cancer patients recruited during 1997–1999 from four geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island; N = 422) were matched by age, race, baseline comorbidity and zip code location with up to four non-breast-cancer controls (N = 1,656). OUTCOMES Survival; numbers of hospitalized days and physician visits; total inpatient and outpatient Medicare payments; guideline monitoring for patients with cardiovascular disease and diabetes, and bone density testing and colorectal cancer screening. RESULTS Five-year survival was similar for cases and controls (80% and 82%, respectively; p = 0.18). In the first follow-up year, comorbidity burden and health care utilization were higher for cases (p < 0.01), with most differences diminishing over time. However, the number of physician visits was higher for cases (p < 0.01) in every year, driven partly by more cancer and surgical specialist visits. Cases and controls adhered similarly to recommended bone density testing, and monitoring of cardiovascular disease and diabetes; adherence to recommended colorectal cancer screening was better among cases. CONCLUSION Breast cancer survivors’ health care utilization and disease burden return to pre-diagnosis levels after one year, yet their greater use of outpatient care persists at least five years. Quality of care for other chronic health problems is similar for cases and controls.

[CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials (Chinese version)]

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials

Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.

Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients

PURPOSE: Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer. EXPERIMENTAL DESIGN: Prostate cancer patients (N = 3,261) treated by radical prostatectomy at a single institution were evaluated by using tissue microarray. Follow-up data were available for 2,385 patients. The cellular domain (membranous, membranous-cytoplasmatic, and cytoplasmatic only) of CD10 expression was analyzed immunohistochemically and correlated with various clinical and histopathologic features of the tumors. RESULTS: CD10 expression was detected in 62.2% of cancer samples and occurred preferentially in higher Gleason pattern (P < 0.0001). CD10 expression positively correlated with adverse tumor features such as elevated preoperative prostate-specific antigen (PSA), higher Gleason score, and advanced stage (P < 0.0001 each). Survival analyses showed that PSA recurrence was significantly associated with the staining pattern of CD10 expression. Outcome significantly declined from negative over membranous, membranous-cytoplasmatic, to exclusively cytoplasmatic CD10 expression (P < 0.0001). In multivariate analysis, CD10 expression was an independent predictor for PSA failure (P = 0.0343). CONCLUSIONS: CD10 expression is an unfavorable independent risk factor in prostate cancer. The subcellular location of CD10 protein is associated with specific clinical courses, suggesting an effect on different important biological properties of prostate cancer cells. The frequent expression of CD10 in prostate cancer and the strong association of CD10 with unfavorable tumor features may qualify this biomarker for targeted therapies.

Design, expression, and processing of epitomized hepatitis C virus-encoded CTL epitopes

Hepatitis C virus (HCV) vaccine efficacy may crucially depend on immunogen length and coverage of viral sequence diversity. However, covering a considerable proportion of the circulating viral sequence variants would likely require long immunogens, which for the conserved portions of the viral genome, would contain unnecessarily redundant sequence information. In this study, we present the design and in vitro performance analysis of a novel "epitome" approach that compresses frequent immune targets of the cellular immune response against HCV into a shorter immunogen sequence. Compression of immunological information is achieved by partial overlapping shared sequence motifs between individual epitopes. At the same time, sequence diversity coverage is provided by taking advantage of emerging cross-reactivity patterns among epitope variants so that epitope variants associated with the broadest variant cross-recognition are preferentially included. The processing and presentation analysis of specific epitopes included in such a compressed, in vitro-expressed HCV epitome indicated effective processing of a majority of tested epitopes, although re-presentation of some epitopes may require refined sequence design. Together, the present study establishes the epitome approach as a potential powerful tool for vaccine immunogen design, especially suitable for the induction of cellular immune responses against highly variable pathogens.

Changing trends in causes and patterns of facial fractures in children

OBJECTIVE: To review the epidemiology of facial fractures in children and to analyze whether it has changed over time. STUDY DESIGN: Retrospective review of records of children aged < or = 15 years diagnosed for fracture during 2 10-year periods. RESULTS: A total of 378 children were diagnosed with fractures, 187 in 1980-1989 and 191 in 1993-2002. The proportion of children with mandibular fractures decreased by 13.6 percentage-points from the first period to the second, whereas the proportion of patients with midfacial fractures increased by 18.7 percentage-points. Assault as a causative factor increased by 5.5 percentage-points, almost exclusively among children aged 13-15 years, with a high percentage (23.5%). CONCLUSIONS: Recognition of a change in fracture patterns over time is probably due to the increased use of computerized tomographic scanning.

fMRI of Emotion

Recent brain imaging work has expanded our understanding of the mechanisms of perceptual, cognitive, and motor functions in human subjects, but research into the cerebral control of emotional and motivational function is at a much earlier stage. Important concepts and theories of emotion are briefly introduced, as are research designs and multimodal approaches to answering the central questions in the field. We provide a detailed inspection of the methodological and technical challenges in assessing the cerebral correlates of emotional activation, perception, learning, memory, and emotional regulation behavior in healthy humans. fMRI is particularly challenging in structures such as the amygdala as it is affected by susceptibility-related signal loss, image distortion, physiological and motion artifacts and colocalized Resting State Networks (RSNs). We review how these problems can be mitigated by using optimized echo-planar imaging (EPI) parameters, alternative MR sequences, and correction schemes. High-quality data can be acquired rapidly in these problematic regions with gradient compensated multiecho EPI or high resolution EPI with parallel imaging and optimum gradient directions, combined with distortion correction. Although neuroimaging studies of emotion encounter many difficulties regarding the limitations of measurement precision, research design, and strategies of validating neuropsychological emotion constructs, considerable improvement in data quality and sensitivity to subtle effects can be achieved. The methods outlined offer the prospect for fMRI studies of emotion to provide more sensitive, reliable, and representative models of measurement that systematically relate the dynamics of emotional regulation behavior with topographically distinct patterns of activity in the brain. This will provide additional information as an aid to assessment, categorization, and treatment of patients with emotional and personality disorders.

Functionalized Adamantane Tectons Used in the Design of Mixed-Ligand Copper(II) 1,2,4-Triazolyl/Carboxylate Metal–Organic Frameworks

Bistriazoles, 1,3-bis(1,2,4-triazol-4-yl)propane (tr2pr) and 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad), were examined in combination with the rigid tetratopic 1,3,5,7-adamantanetetracarboxylic acid (H4-adtc) platform for the construction of neutral heteroleptic copper(II) metal−organic frameworks. Two coordination polymers, [{Cu4(OH)2(H2O)2}{Cu4(OH)2}(tr2pr)2(H-adtc)4]·2H2O (1) and [Cu4(OH)2(tr2ad)2(H-adtc)2(H2O)2]·3H2O (2), were synthesized and structurally characterized. In complexes 1 and 2, the N1,N2-1,2,4-triazolyl (tr) and μ3-OH− groups serve as complementary bridges between adjacent metal centers supporting the tetranuclear dihydroxo clusters. The structure of 1 represents a unique association of two different kinds of centrosymmetrical {Cu4(OH)2} units in a tight 3D framework, while in compound 2, another configuration type of acentric tetranuclear metal clusters is organized in a layered 3,6-hexagonal motif. In both cases, the {Cu4(OH)2} secondary building block and trideprotonated carboxylate H-adtc3− can be viewed as covalently bound six- and three-connected nodes that define the net topology. The tr ligands, showing μ3- or μ4-binding patterns, introduce additional integrating links between the neighboring {Cu4(OH)2} fragments. A variable-temperature magnetic susceptibility study of 2 demonstrates strong antiferromagnetic intracluster coupling (J1 = −109 cm−1 and J2 = −21 cm−1), which combines for the bulk phase with a weak antiferromagnetic intercluster interaction (zj = −2.5 cm−1).

Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease

OBJECTIVE To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. DESIGN Prospective study in consecutive individuals. SETTING University hospital. METHODS Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. RESULTS Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. CONCLUSIONS Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.

Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by heterotopic transplantation

BACKGROUND Mechanical unloading of failing hearts can trigger functional recovery but results in progressive atrophy and possibly detrimental adaptation. In an unbiased approach, we examined the dynamic effects of unloading duration on molecular markers indicative of myocardial damage, hypothesizing that potential recovery may be improved by optimized unloading time. METHODS Heterotopically transplanted normal rat hearts were harvested at 3, 8, 15, 30, and 60 days. Forty-seven genes were analyzed using TaqMan-based microarray, Western blot, and immunohistochemistry. RESULTS In parallel with marked atrophy (22% to 64% volume loss at 3 respectively 60 days), expression of myosin heavy-chain isoforms (MHC-α/-β) was characteristically switched in a time-dependent manner. Genes involved in tissue remodeling (FGF-2, CTGF, TGFb, IGF-1) were increasingly upregulated with duration of unloading. A distinct pattern was observed for genes involved in generation of contractile force; an indiscriminate early downregulation was followed by a new steady-state below normal. For pro-apoptotic transcripts bax, bnip-3, and cCasp-6 and -9 mRNA levels demonstrated a slight increase up to 30 days unloading with pronunciation at 60 days. Findings regarding cell death were confirmed on the protein level. Proteasome activity indicated early increase of protein degradation but decreased below baseline in unloaded hearts at 60 days. CONCLUSIONS We identified incrementally increased apoptosis after myocardial unloading of the normal rat heart, which is exacerbated at late time points (60 days) and inversely related to loss of myocardial mass. Our findings suggest an irreversible detrimental effect of long-term unloading on myocardium that may be precluded by partial reloading and amenable to molecular therapeutic intervention.