Dynamic processes at the ends of collisional mountain chains.

Understanding of the relationships between tectonic deformation and exhumation in the Himalaya remains incomplete, especially at the ends of the chain.

Climate controls on erosion in tectonically active landscapes.

The ongoing debate about the nature of coupling between climate and tectonics in mountain ranges derives, in part, from an imperfect understanding of how topography, climate, erosion, and rock uplift are interrelated. Here, we demonstrate that erosion rate is nonlinearly related to fluvial relief with a proportionality set by mean annual rainfall. These relationships can be quantified for tectonically active landscapes, and calculations based on them enable estimation of erosion where observations are lacking. Tests of the predictive power of this relationship in the Himalaya, where erosion is well constrained, affirm the value of our approach. Our model allows estimation of erosion rates in fluvial landscapes using readily available datasets, and the underlying relationship between erosion and rainfall offers the promise of a deeper understanding of how climate and tectonic evolution affect erosion and topography in space and time and of the potential influence of climate on tectonics.

Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium.

Cell-cell communication is essential for tissue homeostasis, but its contribution to disease prevention remains to be understood. We demonstrate the involvement of connexin 43 (Cx43, also known as GJA1) and related gap junction in epithelial homeostasis, illustrated by polarity-mediated cell cycle entry and mitotic spindle orientation (MSO). Cx43 localization is restricted to the apicolateral membrane of phenotypically normal breast luminal epithelial cells in 3D culture and in vivo Chemically induced blockade of gap junction intercellular communication (GJIC), as well as the absence of Cx43, disrupt the apicolateral distribution of polarity determinant tight junction marker ZO-1 (also known as TJP1) and lead to random MSO and cell multilayering. Induced expression of Cx43 in cells that normally lack this protein reestablishes polarity and proper MSO in 3D culture. Cx43-directed MSO implicates PI3K-aPKC signaling, and Cx43 co-precipitates with signaling node proteins ß-catenin (CTNNB1) and ZO-2 (also known as TJP2) in the polarized epithelium. The distribution of Cx43 is altered by pro-inflammatory breast cancer risk factors such as leptin and high-fat diet, as shown in cell culture and on tissue biopsy sections. The control of polarity-mediated quiescence and MSO may contribute to the tumor-suppressive role of Cx43.

Male patients affected by mosaic PCDH19 mutations: five new cases.

Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females and mosaic males are affected, likely due to a disease mechanism named cellular interference. Until now, only four affected mosaic male patients have been described in literature. Here, we report five additional male patients, of which four are older than the oldest patient reported so far. All reported patients were selected for genetic testing because of developmental delay and/or epilepsy. Custom-targeted next generation sequencing gene panels for epilepsy genes were used. Clinical data were collected from medical records. All patients were mosaic in blood for likely pathogenic variants in the PCDH19 gene. In most, clinical features were very similar to the female phenotype, with normal development before seizure onset, which occurred between 5 and 10 months of age, clustering of seizures and sensitivity to fever. Four out of five patients had mild to severe ID and behavioural problems. We reaffirm the similarity between male and female PCDH19-related phenotypes, now also in a later phase of the disorder (ages 10-14 years).

A novel landscape genetic approach demonstrates the effects of human disturbance on the Udzungwa red colobus monkey (Procolobus gordonorum).

A comprehensive understanding of how human disturbance affects tropical forest ecosystems is critical for the mitigation of future losses in global biodiversity. Although many genetic studies of tropical forest fragmentation have been conducted to provide insight into this issue, relatively few have incorporated landscape data to explicitly test the effects of human disturbance on genetic differentiation among populations. In this study, we use a newly developed landscape genetic approach that relies on a genetic algorithm to simultaneously optimize resistance surfaces to investigate the effects of human disturbance in the Udzungwa Mountains of Tanzania, which is an important part of a universally recognized biodiversity hotspot. Our study species is the endangered Udzungwa red colobus monkey (Procolobus gordonorum), which is endemic to the Udzungwa Mountains and a known indicator species that thrives in large and well-protected blocks of old growth forest. Population genetic analyses identified significant population structure among Udzungwa red colobus inhabiting different forest blocks, and Bayesian cluster analyses identified hierarchical structure. Our new method for creating composite landscape resistance models found that the combination of fire density on the landscape and distance to the nearest village best explains the genetic structure observed. These results demonstrate the effects that human activities are having in an area of high global conservation priority and suggest that this ecosystem is in a precarious state. Our study also illustrates the ability of our novel landscape genetic method to detect the impacts of relatively recent landscape features on a long-lived species.

Dentinal sensitivity: a natural mineral dietary supplement study.

The purpose of the investigation was to determine the effect of drinking a natural mineral dietary supplement (NMDS) on gingival health and dentinal hypersensitivity. The NMDS product was from a geothermal source and contained 3.6 mg l(-1) of fluoride and other minerals. Sample selection included subjects with gingival inflammation and sensitivity as well as screening for exclusion factors. A double-blind randomized parallel approach was used. The investigation was a quasi-experimental pre/post-test design. The experimental group ingested and swished twice a day with the NMDS (1 l) and the control group followed the same regimen with a placebo containing de-ionized water (DIW). Clinical measurements of gingival inflammation and dentinal sensitivity were taken at baseline, 4 and 8 weeks. Gingival inflammation was measured using the Gingival Index. Dentinal hypersensitivity was measured using a tactile stimulus and an evaporative stimulus. After each stimulus was applied, the subjects rated the amount of discomfort on a visual analogue scale from 0 to 10. Each set of data was analysed using anova and a post hoc probing technique to determine within- and between-group differences (P = 0.05). The experimental and control groups (n = 70) experienced a statistically significant decrease in tactile and evaporative sensitivity scores over time; however, the between-group differences were not significant. The gingival inflammation data were not statistically significant with regard to the within- and between-group differences. Therefore the NMDS and DIW were equally effective in reducing dentinal hypersensitivity and neither product effectively reduced gingival inflammation.

READIT: a novel technology used in the interrogation of nucleic acid sequences for single-nucleotide polymorphisms.

The ability to perform analyses for single-nucleotide polymorphisms (SNPs) has become routine in many molecular diagnostic laboratories. While various procedures and technologies are available to do so, we evaluated a novel technology for SNP analysis using the Factor V Leiden polymorphism as an example. The Factor V Leiden polymorphism G1691A is the most common genetic abnormality associated with hereditary thrombophilia. Current testing methods remain highly accurate yet their main disadvantage is gel-based detection. The READIT System (Promega Corp., Madison, WI) is a novel approach to SNP analysis that utilizes DNA polymerase-mediated pyrophosphorolysis to release dNTPs, which are converted to ATP and used in a luciferase detection reaction. We screened 280 DNA specimens, previously analyzed using the PCR/MnlI restriction digest assay, to evaluate READIT System capabilities along with the KingFisher robotic magnetic particle processor (ThermoLabsystems). Concordant results were obtained for 278/280 (99%) specimens. One discordant result was due to an equivocal relative light unit while the other was indeterminate. Both specimens gave correct results upon repeat analysis. The READIT System offers several advantages including: (1) rapid SNP analysis, (2) accuracy and precision, (3) cost effectiveness, (4) decreased turn-around times, (5) high throughput, and (6) excellent analysis software.

Prioritization of professional issues by Idaho Dental Hygienists.

PURPOSE: The Idaho Dental Hygienists' Association (IDHA) and other constituents use surveys to establish the goals of the association and better represent members. This study was conducted to assess dental hygienists' opinions about professional issues related to dental hygiene practice and legislative activities in Idaho. METHODS: In 1998, a questionnaire was mailed to all active Idaho dental hygiene licensees (N = 652). The coded questionnaire contained two sections. Section I included items on demographic and employment characteristics, and Section II included items on legislative and professional issues. Respondents were asked to rank 14 professional issues by selecting the top five concerns about dental hygiene practice in Idaho. Research questions asked included: 1) Do entry-level baccalaureate degrees in dental hygiene affect the ranking of professional concerns of Idaho dental hygienists? 2) Does being a member of the American Dental Hygienists' Association (ADHA) affect Idaho dental hygienists' ranking of professional concerns? Data were analyzed using frequency distributions and nonparametric tests of association. RESULTS: A 74% (N = 431) response rate was obtained after two mailings. Three professional issues were ranked as important concerns by at least 50% of respondents. They were 1) the "national trend to reduce entry-level education for dental hygienists," 2) "dental assistants performing dental hygiene services," and 3) "legalizing self-regulation." CONCLUSIONS: It is incumbent upon constituent dental hygienists' associations to obtain and utilize information from members for strategic planning and legislative efforts. A statewide membership study clearly can provide direction. Idaho dental hygienists are concerned about maintaining quality education programs, reducing illegal practices, and regulating themselves. Also, the state association and regulatory agencies need to take an active role to assure that dentists, dental hygienists, and dental assistants are educated about state laws.

Relation of plasma oxytocin and prolactin concentrations to milk production in mothers of preterm infants: influence of stress.

Responses of oxytocin and PRL to mechanical breast pumping and the influence of physiological indicators of stress were measured at 2, 4, and 6 weeks postpartum to determine potential causes of inadequate milk production in 18 women with prematurely delivered, nonnursing (<1500 g) infants. Median milk production was similar to that reported in breastfeeding mothers, but a third of mothers were producing less than half as much by week 6. Plasma oxytocin was similar to that previously reported for breastfeeding mothers. The oxytocin area under the curve (AUC) for breast-pumping sessions (70 min) was correlated at each occasion (r = 0.37, 0.58, and 0.55, respectively) with milk yield. Unlike reports of PRL levels in breast-feeding women, PRL AUC declined between weeks 2 and 6 weeks postpartum (P = 0.03); significant increases in plasma PRL occurred in response to pumping at 2 and 4 weeks, but not at 6 weeks. Salivary amylase, a measure of alpha-adrenergic activity, was highly negatively correlated on each occasion with PRL AUC (r = -0.58, -0.68, and -0.86, respectively), but not with oxytocin. Salivary cortisol was negatively correlated to a lesser degree. We hypothesize that deficiencies in preterm lactation are mediated in part upon stress-induced suppression of PRL secretion through an adrenergic mechanism.

Client typology based on functioning across domains using the CAFAS: implications for service planning.

Cluster analysis was used to develop a five-group typology based on the eight subscales of the Child and Adolescent Functional Assessment Scale (CAFAS) using data on 4,758 youths referred to Community Mental Health Service Providers in Michigan. The groups are described in terms of clinical diagnoses, overall impairment in functioning, past and current use of services from other agencies (i.e., juvenile justice, social services), and caregiver resourcefulness. From most to least impaired, the clusters were the following: Substance Users/Externalizers, Comorbid/Self-Harmful, Delinquents, Marked/School Problems, and Adjustment Problems with Impairment/Secondary Prevention. The results are being used to help identify the most impaired youths with serious emotional disturbance (SED) youths, develop specific programs and services for the different types of youths being served, determine staff training needs, and foster clinical practice in which the youth's progress is continually monitored.

Psychometric study of the Child and Adolescent Functional Assessment Scale: prediction of contact with the law and poor school attendance.

The predictive validity of the Child and Adolescent Functional Assessment Scale (CAFAS) is investigated using the data set generated by the national evaluation of the demonstration service grants funded by the Center for Mental Health Services. Logistic regressions were performed separately for contact with the law and poor school attendance, which were both assessed at 6 months postintake. Other variables included in the model besides the CAFAS total score at intake were age, gender, and family risk factors. The results show that the CAFAS total score at intake was a positive predictor of the likelihood of contact with the law and poor school attendance, even after controlling for age, gender, and risk factors. Furthermore, the CAFAS total score was predictive even after excluding scores on CAFAS subscales, which may have been influenced by absenteeism or delinquency. These findings are consistent with recent research indicating that the CAFAS predicts recidivism in juvenile delinquents.

Hormonal correlates of reproductive seasonality in wild female hanuman langurs (Presbytis entellus).

To date, it is not known whether the seasonal occurrence of sexual behavior and mating in free-ranging Hanuman langurs at Ramnagar, Nepal, is correlated with seasonal changes in female ovarian function, and, if so, which factor(s) triggers the onset of the reproductive period. Using noninvasive fecal hormone analysis in combination with behavioral observations, this study was carried out to: 1) investigate and characterize seasonal patterns of ovarian cyclicity and timing of conception in wild langur females living in a highly seasonal habitat; and 2) examine the relationship between seasonal patterns of ovarian cyclicity, behavioral estrus, and female physical condition. Behavioral data and fecal samples were collected during a total period of 14 months from nine females living in a multi-male group. Physical condition of the females was assessed monthly by visual inspection, using a seven-fold scale. Ovulatory cycles and timing of conceptions were identified by the measurement of immunoreactive pregnanediol glucuronide (iPdG) in extracted feces. Hormone profiles in individual females revealed a clearly seasonal distribution in the occurrence of ovulatory cycles, which were restricted to the period from July to October. The distribution of female estrus behavior showed a similar seasonal pattern, and in total 88.2% of all estrus periods observed in the focal females were accompanied by ovulation. Onset of ovarian cycles as well as mating activities were strongly correlated with the onset of the rainy season. Females conceived, on average, in their second ovulatory cycle (pregnancy length: 211.6 +/- 3.4 days), with timing of conception being confined to the months when animals showed an improved physical condition. Collectively the present data clearly suggest that in seasonally-breeding langurs at Ramnagar, ecological conditions (rainfall, food availability, and quality) influence the onset of ovulations and timing of conceptions.

Predicting service utilization with the Child and Adolescent Functional Assessment Scale in a sample of youths with serious emotional disturbance served by center for mental health services-funded demonstrations.

This study investigated level of restrictiveness of living arrangements and number of days in out-of-family care at six months postintake, based on the Child and Adolescent Functional Assessment Scale (CAFAS), the Child Behavior Checklist (CBCL), gender, age, and level of family income at intake. It was composed of youths who met the criteria for serious emotional disturbance (SED) and were for the most part living in families that are described as socioeconomically disadvantaged. A multinomial logit model was used in the analysis of level of restrictiveness of living arrangements, and an ordinary least squares (OLS) regression model was conducted on number of days in out-of-family care. The CAFAS score at intake was found to be a significant predictor of service utilization between intake and six months and was a more consistent predictor than the CBCL. Results suggest that the CAFAS can be used to match service needs with resource allocation and to monitor performance-based outcome indicators.

Nutrition and health (1948) of Aborigines in settlements in Arnhem Land, northern Australia.

During the American-Australian Scientific Expedition to Arnhem Land in 1948, a nutritionist (Margaret McArthur), a medical officer (Brian Billington), a biochemist (Kelvin Hodges) and also the 'flying dentist' (John Moody) observed the nutrition and health of Aborigines in the settlements on Groote Eylandt, at Yirrkala and at Oenpelli, Northern Territory. The results of their research were published in the Records of the American-Australian Scientific Expedition to Arnhem Land Volume 2 Anthropology and Nutrition. (Melbourne University Press, 1960). Although seasonal and regional variations in food supply were a constant problem for nomadic Aborigines living on 'bush tucker' gathered from marine, freshwater and terrestrial ecosystems, the variety of food provided a well-balanced diet according to the international recommendations of 1948. In contrast, improvements in the 1948 diet of Aborigines in the settlements were strongly recommended. 1 An increase in the quantity of food given to older children and adolescents. 2 Regular distribution of fresh fruit and vegetables throughout the year from settlement gardens. 3 Regular supplies of fish, meat and other animal products, particularly for children, adolescents, pregnant and lactating mothers. 4 Increased production of milk and greater care in its handling. 5 Greater use of whole grain cereals in preference to refined products.

Salivary estradiol and progesterone levels in conception and nonconception cycles in women: evaluation of a new assay for salivary estradiol.

OBJECTIVE: To determine the usefulness of salivary E2 and progesterone for noninvasive assessment of ovarian function. DESIGN: Prospective study of salivary hormone levels in women planning a pregnancy. SETTING: Department of Obstetrics and Gynecology at Northwestern University Medical School in Chicago, Illinois. PATIENT(S): Fourteen women aged 23-39 years with regular menstrual cycles who were planning a pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Salivary estradiol and progesterone concentrations. RESULT(S): The sensitivity of the E2 assay is 2.0 pmol/L; the interassay coefficient of variation was 5.2% (mean value 17 pmol/L). Recovery of E2 added to saliva was 106%. The correlation with simultaneous serum samples was 0.71. Menstrual cycle patterns contained a preovulatory depression and a midcycle surge. By comparison with nonconception cycles, the luteal phases of conception cycles had significantly elevated salivary E2 within the first 5 days after ovulation. Salivary progesterone was significantly elevated but not until 10 days after ovulation. CONCLUSION(S): Salivary measurements of E2 and progesterone can be used as noninvasive methods for assessment of ovarian function. Salivary specimens can be collected at home and brought to the laboratory for analysis, obviating the need for frequent phlebotomy. The sensitivity and precision of the salivary E2 assay make it comparable with assays of serum E2 for assessing changes in hormone levels.

Rarity of genomic instability in pathogenesis of systemic anaplastic large cell lymphoma (ALCL) in immunocompetent patients.

Microsatellite instability (MSI) is a recently described type of genetic alteration resulting from defects in the DNA mismatch repair genes that appears to play an integral role in neoplastic transformation. MSI has been described in a wide variety of malignancies; however, data regarding the role of MSI in the pathogenesis of non-Hodgkin's lymphoma (NHL) are limited. MSI appears to be important in some T-cell lymphomas, including ALCL arising in immunocompromised patients. In addition, MSI has recently been identified in CD30+ cutaneous lymphoproliferative processes and lymphoblastic lymphoma. In this study, we have analyzed five well-characterized cases of systemic T-cell ALCL arising in immunocompetent patients for the presence of MSI. Genomic DNA isolated from paired normal and tumor tissue was analyzed at seven microsatellite loci by polymerase chain reaction. We were unable to identify MSI or loss of heterozygosity (LOH) in our cases, suggesting that abnormalities in the DNA mismatch repair system do not play a major role in the pathogenesis of most systemic ALCL. Our data provide additional molecular evidence that the various subgroups of lymphoma with ALCL morphology are biologically distinct processes.

Transformation of the small cell variant Ki-1+ lymphoma to anaplastic large cell lymphoma: pathologic and clinical features.

The disease spectrum of anaplastic large cell lymphoma (ALCL) includes a biologically aggressive small cell variant (SCV). The SCV may progress to ALCL, but little is known about the transformation process and its significance. The goals of this study were (1) to identify the clinical and pathologic features that characterize ALCL arising in SCV and (2) to determine whether some cases with ALCL histologic appearance at the outset arose from an SCV. Seventeen SCV were reviewed, and four cases (24%) transformed to ALCL as shown by subsequent biopsy. The ALCLs were predominantly monomorphic (3 cases) rather than pleomorphic (1 case). Residual SCV was detected at transformation in 3 of 4 cases. Twenty-one de novo T-cell ALCLs were reviewed for an SCV component; such a component was identified in two ALCLs with monomorphic features, suggesting a preceding SCV phase. There was no change in the immunophenotype between the SCV and ALCL, all marking as EMA+ T cells. Expression of p80 was detected in 3 of 4 (75%) SCV with transformation and 10 of 12 (77%) SCV without transformation. Chromosomal abnormalities involving the sex chromosomes and 6, 7, 9, and 15, in addition to the characteristic t(2;5)(p23;q35), were present in 2 cases at transformation. Times to transformation ranged from 1 to 146 months (mean: 63 months) after diagnosis. Transformation to ALCL signaled a rapid clinical course, with 75% of patients dying in less than a year; one patient remains alive at 15 months. In summary, some ALCLs, particularly those with monomorphic features, arise from an SCV. Transformation to ALCL signals a rapid course, with death occurring in less than a year in most cases. Necrosis in the SCV may be predictive of transformation. Chromosomal abnormalities in addition to the t(2;5)(p23;q35) are present at transformation, suggesting that multiple genetic alterations are involved in disease progression.