Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype-phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions.

The Secular State Under Siege: Religion and Politics in Europe and America

Throughout human history, religion and politics have entertained the most intimate of connections as systems of authority regulating individuals and society. While the two have come apart through the process of secularization, secularism is challenged today by the return of public religion. This cogent analysis unravels the nature of the connection, disconnection, and attempted reconnection between religion and politics in the West. In a comparison of Western Europe and North America, Christianity and Islam, Joppke advances far-reaching theoretical, historical, and comparative-political arguments. With respect to theory, it is argued that only a “substantive” concept of religion, as pertaining to the existence of supra-human powers, opens up the possibility of a historical-comparative perspective on religion. At the level of history, secularization is shown to be the distinct outcome of Latin Christianity itself. And at the level of comparative politics, the Christian Right in America which has attacked the “wall of separation” between religion and state and Islam in Europe with the controversial insistence on sharia law and other “illiberal” claims from some quarters are taken to be counterpart incarnations of public religion and challenges to the secular state. This clearly argued, sweeping book will provide an invaluable framework for approaching an array of critical issues at the intersection of religion, law and politics for advanced students and researchers across the social sciences and legal studies, as well as for the interested public.

Primary lowland dipterocarp forest at Danum Valley, Sabah, Malaysia. Species composition and patterns in the understorey

The spatial distributions of species of tree ≥10 cm gbh were examined in two 4 ha plots and related to the local variation in topography and soil chemistry. The plots were similar in their species composition, particularly in terms of the densities of small trees, and they showed very similar edaphic characteristics. Size class distributions varied little within and between plots. Ordination of 0.25 ha subplots highlighted parallel gradients in the vegetation of both plots when the densities of trees ≥10 cm gbh were considered. Focusing on understorey trees in the 10-<50 cm gbh class at the 0.04 ha subplot scale showed a similar vegetation gradient in both plots closely associated with change from lower slope to ridge. No relationship with soil chemistry was found. On the ridges a special group of understorey species formed clumps and these species contributed importantly to the ordinations. Borneo has a regional history of occasionally severe droughts. It is suggested here that the observed patterns in the understorey are due to differential responses to low soil water supply, the ridges probably tending to dryness more than the lower slopes. Within the large and diverse family Euphorbiaceae, which dominates the understorey at Danum, there may be ecophysiological groupings of species. The long-term effects of disturbance interacting with local edaphic factors on forest structure and composition are discussed.

Anadromous Rainbow Smelt and Tomcod in Connecticut: Assessment of populations, conservation status, and need for restoration plan

(beginning of rainbow smelt executive summary) Evidence indicates that anadromous rainbow smelt (Osmerus mordax) populations in Connecticut and elsewhere in the northeast United States have severely declined. Several sampling programs have documented declines in Connecticut’s smelt populations over the last three decades (Marcy 1976a, Marcy 1976b, Millstone Environmental Laboratory 2005). Similar declines have also been documented in the Hudson River (ASA Analysis & Communication 2005) and in Massachusetts (personal communication, Brad Chase, MA Division of Marine Fisheries 2004). Recreational and commercial fisheries in the region for this species have virtually ceased (Blake and Smith 1984). The Connecticut Fish Advisory Committee of the Endangered Species Program has recommended that rainbow smelt be listed as threatened in Connecticut, and the National Marine Fisheries Service (2004) has recently listed rainbow smelt as a Federal Species of Concern. The purpose of this project is to develop an environmental history of rainbow smelt in Connecticut and surrounding regions, and document the current status of populations in Connecticut waters. An environmental history that assesses trends in abundance, environmental threats and historical efforts to ameliorate the threats will contribute to regional efforts to conserve these fish. Comprehensive review of the regional literature and trends associated with rainbow smelt has not been undertaken since Kendall (1926). Assessment of current abundance, distribution, areas of critical habitat, and whether the species is presently reproducing in state waters is critical for clarifying conservation status, designing a monitoring program and developing a recovery or enhancement plan, if this appears to be necessary. (beginning of tomcod executive summary) Atlantic tomcod (Microgadus tomcod) are believed to have declined significantly in Connecticut and other estuaries of the Northeast and Middle Atlantic states. Several monitoring programs indicate that the species is scarce and/or declining in the region’s estuaries (Gottschall and Pacileo 2004, Molnar 2004, Millstone Environmental Laboratory 2005, ASA Analysis and Communication 2005). Once-active recreational (NMFS MRFSS 2005, http://www.st.nmfs.gov) and commercial fisheries for this species in Connecticut are now dormant. For the past 10 years, the Connecticut Fish Advisory Committee of the Endangered Species Program has recommended that studies be undertaken to quantify the status of tomcod populations and to determine if conservation actions should be initiated. The purpose of this project is to develop an environmental history of Atlantic tomcod in Connecticut and surrounding regions, and document the current status of populations in Connecticut waters. An environmental history that assesses trends in abundance, environmental threats and historical efforts to ameliorate the threats will contribute to regional efforts to conserve these fish. Assessment of current abundance, distribution, areas of critical habitat, and whether the species is presently reproducing in state waters is critical for determining conservation status, designing a monitoring program and developing a recovery or enhancement plan, if this appears to be necessary.

Expectations, and Credibility in a Model of Monetary Policy

Recent monetary history has been characterized by monetary authorities which have been, alternatively hard and soft on inflation. In a vintage capital framework, investment decisions are not easily reversed. Therefore, expectations of policy as well as current policy are important to the investment decision. Here, a vintage capital model is used to assess the value of central bank credibility for a policy change. Policy in this model is assumed to be private information of the central banker. Agents learn about that policy which to study the ensuing transitional dynamics following a change in monetary policy regime.

Tax Collection in History

Methods of tax collection employed by modern governments seem dull when compared to the rich variety observed in history. Whereas most governments today typically use salaried agents to collect taxes, various other types of contractual relationships have been observed in history, including sharing arrangements which divide the tax revenue between the government and collectors at fixed proportions, negotiated payment schemes based on the tax base, and sale of the revenue to a collector in exchange for a lump-sum payment determined at auction. We propose an economic theory of tax collection that can coherently explain the temporal and spatial variation in contractual forms. We begin by offering a simple classification of tax collection schemes observed in history. We then develop a general economic model of tax collection that specifies the cost and benefits of alternative schemes and identifies the conditions under which a government would choose one contractual form over another in maximizing the net revenue. Finally, we use the conclusions of the model to explain some of the well-known patterns of tax collection observed in history and how choices varied over time and space.

Polynesian mythology and ancient traditional history of the New Zealand race as furnished by their priests and chiefs

by Sir George Grey, late governor-in-chief in New Zealand

Catalogue of Hebraica and Judaica in the library of the Corporation of the City of London

by A. Löwy

The role of smoking status on postoperative complications and survival in lung cancer patients presenting to M.D. Anderson Cancer Center

It is estimated that 50% of all lung cancer patients continue to smoke after diagnosis. Many of these lung cancer patients who are current smokers often experience tremendous guilt and responsibility for their disease, and feel it might be too late for them to quit smoking. In addition, many oncologists may be heard to say that it is 'too late', 'it doesn't matter', 'it is too difficult', 'it is too stressful' for their patients to stop smoking, or they never identify the smoking status of the patient. Many oncologists feel unprepared to address smoking cessation as part of their clinical practice. In reality, physicians can have tremendous effects on motivating patients, particularly when patients are initially being diagnosed with cancer. More information is needed to convince patients to quit smoking and to encourage clinicians to assist patients with their smoking cessation. ^ In this current study, smoking status at time of lung cancer diagnosis was assessed to examine its impact on complications and survival, after exploring the reliability of smoking data that is self-reported. Logistic Regression was used to determine the risks of smoking prior to lung resection. In addition, survival analysis was performed to examine the impact of smoking on survival. ^ The reliability of how patients report their smoking status was high, but there was some discordance between current smokers and recent quitters. In addition, we found that cigarette pack-year history and duration of smoking cessation were directly related to the rate of a pulmonary complication. In regards to survival, we found that current smoking at time of lung cancer diagnosis was an independent predictor of early stage lung cancer. This evidence supports the idea that it is "never too late" for patients to quit smoking and health care providers should incorporate smoking status regularly into their clinical practice.^

Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

Ethnic differences in tumor characteristics, treatment and survival in glioma patients

Purpose. A descriptive analysis of glioma patients by race was carried out in order to better elucidate potential differences between races in demographics, treatment, characteristics, prognosis and survival. ^ Patients and Methods. Among 1,967 patients ≥ 18 years diagnosed with glioma seen between July 2000 and September 2006 at The University of Texas M.D. Anderson Cancer Center (UTMDACC). Data were collated from the UTMDACC Patient History Database (PHDB) and the UTMDACC Tumor Registry Database (TRDB). Chi-square analysis, uni- /multivariate Cox proportional hazards modeling and survival analysis were used to analyze differences by race. ^ Results. Demographic, treatment and histologic differences exist between races. Though risk differences were seen between races, race was not found to be a significant predictor in multivariate regression analysis after accounting for age, surgery, chemotherapy, radiation, tumor type as stratified by WHO tumor grade. Age was the most consistent predictor in risk for death. Overall survival by race was significantly different (p=0.0049) only in low-grade gliomas after adjustment for age although survival differences were very slight. ^ Conclusion. Among this cohort of glioma patients, age was the strongest predictor for survival. It is likely that survival is more influenced by age, time to treatment, tumor grade and surgical expertise rather than racial differences. However, age at diagnosis, gender ratios, histology and history of cancer differed significantly between race and genetic differences to this effect cannot be excluded. ^

Exposure to nonsteroidal anti-inflammatory drugs and weight loss and hospitalization in non-small cell lung cancer patients

Background. Cancer cachexia is a common syndrome complex in cancer, occurring in nearly 80% of patients with advanced cancer and responsible for at least 20% of all cancer deaths. Cachexia is due to increased resting energy expenditure, increased production of inflammatory mediators, and changes in lipid and protein metabolism. Non-steroidal anti-inflammatory drugs (NSAIDs), by virtue of their anti-inflammatory properties, are possibly protective against cancer-related cachexia. Since cachexia is also associated with increased hospitalizations, this outcome may also show improvement with NSAID exposure. ^ Design. In this retrospective study, computerized records from 700 non-small cell lung cancer patients (NSCLC) were reviewed, and 487 (69.57%) were included in the final analyses. Exclusion criteria were severe chronic obstructive pulmonary disease, significant peripheral edema, class III or IV congestive heart failure, liver failure, other reasons for weight loss, or use of research or anabolic medications. Information on medication history, body weight and hospitalizations was collected from one year pre-diagnosis until three years post-diagnosis. Exposure to NSAIDs was defined if a patient had a history of being treated with NSAIDs for at least 50% of any given year in the observation period. We used t-test and chi-square tests for statistical analyses. ^ Results. Neither the proportion of patients with cachexia (p=0.27) nor the number of hospitalizations (p=0.74) differed among those with a history of NSAID use (n=92) and those without (n=395). ^ Conclusions. In this study, NSAID exposure was not significantly associated with weight loss or hospital admissions in patients with NSCLC. Further studies may be needed to confirm these observations.^