Defective WNT signaling associates with bone marrow fibrosis-a cross-sectional cohort study in a family with WNT1 osteoporosis

This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology. We aimed to explore bone marrow findings in a large family with early-onset osteoporosis due to a heterozygous WNT1 mutation. We analyzed peripheral blood samples, and bone marrow aspirates and biopsies from 10 subjects with WNT1 mutation p.C218G. One subject was previously diagnosed with idiopathic myelofibrosis and others had no previously diagnosed hematologic disorders. The findings were correlated with the skeletal phenotype, as evaluated by number of peripheral and spinal fractures and bone mineral density. Peripheral blood samples showed no abnormalities in cell counts, morphology or distributions but mild increase in platelet count. Bone marrow aspirates (from 8/10 subjects) showed mild decrease in bone marrow iron storages in 6 and variation in cell distributions in 5 subjects. Bone marrow biopsies (from 6/10 subjects) showed increased bone marrow reticulin (grade MF-2 in the myelofibrosis subject and grade MF-1 in 4 others), and an increase in overall, and a shift towards early-phase, granulopoiesis. The bone marrow findings did not associate with the severity of skeletal phenotype. Defective WNT signaling associates with a mild increase in bone marrow reticulin and may predispose to myelofibrosis, while overall hematopoiesis and peripheral blood values are unaltered in individuals with a WNT1 mutation. In this family with WNT1 osteoporosis, bone marrow findings were not related to the severity of osteoporosis.Peer reviewe

The stability of life satisfaction in a 15-year follow-up of adult Finns healthy at baseline

BACKGROUND: While physical health has improved considerably over recent decades in Finland, the disease burden of mental health, especially that of depression, has become increasingly demanding. However, we lack long-term data on the natural course of subjective well-being in the general population. The aim of this study was to investigate the long-term course of self-reported life satisfaction. METHODS: This was a 15-year prospective cohort study on a nationwide sample of adult Finnish twins (N = 9679), aged 18–45 and healthy at baseline, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction scale (happiness/easiness/interest in life and feelings of loneliness). Life satisfaction score (range: 4–20) was classified into three categories: satisfied (4–6), intermediate (7–11) and dissatisfied group (12–20). The associations between life satisfaction scores during the follow-up were studied with linear/logistic regression. RESULTS: Moderate stability and only a slight effect of age or birth-cohort on mean life satisfaction score (LS) were detected. In 1990, 56% of all and 31% of the dissatisfied remained in the same LS category as at baseline. Only 5.9% of the study subjects changed from being satisfied to dissatisfied or vice versa. Correlations between continuous scores (1975, 1981 and 1990) were 0.3–0.4. Baseline dissatisfaction (compared to satisfaction) predicted dissatisfaction in 1981 (OR = 10.4; 95%CI 8.3–13.1) and 1990 (5.6; 4.6–6.8). Multiple adjustments decreased the risk only slightly. CONCLUSIONS: Life satisfaction in adult Finns was moderately stable during 15 years. Among an identifiable group (i.e. the dissatisfied) life dissatisfaction may become persistent, which places them at a greater risk of adverse health outcomes

Ion-Exchanged Waveguides in Glass Doped with PbS Quantum Dots

The lowest-loss (≤1 dB/cm) ion-exchanged waveguides in glass doped with PbS quantum dots are presented. Near-field mode profile and refractive index profile using the refracted near-field technique were measured for these waveguides. We demonstrate that the optical properties of this glass unchanged during the ion-exchange process

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort.

BACKGROUND: Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. AIM: To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. METHODS: We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n=10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. RESULTS: Parental psychosis was associated (P<0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df]=1; 95% confidence interval [95% CI]: 1.07-5.66) and touching the thumb with the index finger (HR: 1.84; df=1; 95% CI: 1.11-3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df=1; 95% CI: 1.08-3.25) when risk of schizophrenia was investigated. CONCLUSIONS: Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia.This study was supported by grants from the Brain and Behavior Research Foundation, Northern Finland Health Care Support Foundation, Sigrid Jusélius Foundation, and the Signe and Ane Gyllenberg Foundation, Finland. NFBC 1966 received financial support from the Academy of Finland (104781, 120315, 129269, 1114194, 24300796, 268336, 278286), Center of Excellence in Complex Disease Genetics and SALVE, Oulu University Hospital, Oulu, Finland, Biocenter of Oulu, Finland, University of Oulu, Finland (75617, 24002054, 2400692), Ministry of Social Affairs and Health (50459, 50691, 50842, 2749, 2465), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), ENGAGE project and grant agreement HEALTH-F4-2007-(201413), EU FP7 EurHEALTHAgeing (277849), EU FP7 EurHealth Epi-Migrant (279143), European Regional Development Fund 537/2010 (24300936) and the Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.eurpsy.2015.04.00

Is shape in the eye of the beholder? Assessing landmarking error in geometric morphometric analyses on live fish

Geometric morphometrics is widely used to quantify morphological variation between biological specimens, but the fundamental influence of operator bias on data reproducibility is rarely considered, particularly in studies using photographs of live animals taken under field conditions. We examined this using four independent operators that applied an identical landmarking scheme to replicate photographs of 291 live Atlantic salmon (Salmo salar L.) from two rivers. Using repeated measures tests, we found significant inter-operator differences in mean body shape, suggesting that the operators introduced a systematic error despite following the same landmarking scheme. No significant differences were detected when the landmarking process was repeated by the same operator on a random subset of photographs. Importantly, in spite of significant operator bias, small but statistically significant morphological differences between fish from the two rivers were found consistently by all operators. Pairwise tests of angles of vectors of shape change showed that these between-river differences in body shape were analogous across operator datasets, suggesting a general reproducibility of findings obtained by geometric morphometric studies. In contrast, merging landmark data when fish from each river are digitised by different operators had a significant impact on downstream analyses, highlighting an intrinsic risk of bias. Overall, we show that, even when significant inter-operator error is introduced during digitisation, following an identical landmarking scheme can identify morphological differences between populations. This study indicates that operators digitising at least a sub-set of all data groups of interest may be an effective way of mitigating inter-operator error and potentially enabling data sharing

National Income and Income Inequality, Family Affluence and Life Satisfaction Among 13 year Old Boys and Girls: A Multilevel Study in 35 Countries

Adolescence is a critical period where many patterns of health and health behaviour are formed. The objective of this study was to investigate cross-national variation in the relationship between family affluence and adolescent life satisfaction, and the impact of national income and income inequality on this relationship. Data from the 2006 Health Behaviour in School-aged Children: WHO collaborative Study (N = 58,352 across 35 countries) were analysed using multilevel linear and logistic regression analyses for outcome measures life satisfaction score and binary high/low life satisfaction. National income and income inequality were associated with aggregated life satisfaction score and prevalence of high life satisfaction. Within-country socioeconomic inequalities in life satisfaction existed even after adjustment for family structure. This relationship was curvilinear and varied cross-nationally. Socioeconomic inequalities were greatest in poor countries and in countries with unequal income distribution. GDP (PPP US$) and Gini did not explain between country variance in socioeconomic inequalities in life satisfaction. The existence of, and variation in, within-country socioeconomic inequalities in adolescent life satisfaction highlights the importance of identifying and addressing mediating factors during this life stage

Impact-parameter dependent nuclear parton distribution functions: EPS09s and EKS98s and their applications in nuclear hard processes

We determine the spatial (impact parameter) dependence of nuclear parton distribution functions (nPDFs) using the $A$-dependence of the spatially independent (averaged) global fits EPS09 and EKS98. We work under the assumption that the spatial dependence can be formulated as a power series of the nuclear thickness functions $T_A$. To reproduce the $A$-dependence over the entire $x$ range we need terms up to $[T_A]^4$. As an outcome, we release two sets, EPS09s (LO, NLO, error sets) and EKS98s, of spatially dependent nPDFs for public use. We also discuss the implementation of these into the existing calculations. With our results, the centrality dependence of nuclear hard-process observables can be studied consistently with the globally fitted nPDFs for the first time. As an application, we first calculate the LO nuclear modification factor $R^{1jet}_{AA}$ for primary partonic-jet production in different centrality classes in Au+Au collisions at RHIC and Pb+Pb collisions at LHC. Also the corresponding central-to-peripheral ratios $R_{CP}^{1jet}$ are studied. We also calculate the LO and NLO nuclear modification factors for single inclusive neutral pion production, $R_{dAu}^{\pi^0}$, at mid- and forward rapidities in different centrality classes in d+Au collisions at RHIC. In particular, we show that our results are compatible with the PHENIX mid-rapidity data within the overall normalization uncertainties given by the experiment. Finally, we show our predictions for the corresponding modifications $R_{pPb}^{\pi^0}$ in the forthcoming p+Pb collisions at LHC.Comment: 36 page

High pT hadron spectra at RHIC: an overview

Recent results on high transverse momentum (pT) hadron production in p+p, d+Au and Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC) are reviewed. Comparison of the nuclear modification factors, $R_{dAu}(pT)$ and $R_{AA}(pT)$, demonstrates that the large suppression in central Au+Au collisions is due to strong final-state effects. Theoretical models which incorporate jet quenching via gluon Bremsstrahlung in the dense partonic medium that is expected in central Au+Au collisions at ultra-relativistic energies are shown to reproduce the shape and magnitude of the observed suppression over the range of collision energies so far studied at RHIC.Comment: 12 pages, 10 figures, Talk given at Hot Quarks 2004: Workshop for Young Scientists on the Physics of Ultrarelativistic Nucleus-Nucleus Collisions (HQ'04), Taos Valley, New Mexico, 18-24 Jul 2004, to be published in J. Phys.

Sterile leukocyturia is associated with interstitial fibrosis and tubular atrophy in kidney allograft protocol biopsies.

Kidney allograft interstitial fibrosis and tubular atrophy (IF/TA) is associated with a poorer renal function and outcome. In the current clinical practice, an early diagnosis can only be provided by invasive tests. We aimed to investigate the association of sterile leukocyturia with Banff criteria histological findings in kidney allograft protocol biopsies. We studied 348 allograft biopsies from two different European countries performed at 8.5 + 3.5 months after transplantation. In these cases, the presence of sterile leukocyturia (Leuc+, n = 70) or no leukocyturia (Leuc-, n = 278) was analyzed and related to Banff elementary lesions. Only IF/TA was significantly different between Leuc+ and Leuc- groups. IF/TA was present in 85.7% of Leuc+ and 27.7% of Leuc- patients (p < 0.001). IF/TA patients had higher serum creatinine and presence of proteinuria (p < 0.05). Independent predictors of IF/TA were donor age, donor male sex, serum creatinine and Leuc+ (hazard ratio 18.2; 95% confidence interval, 8.1-40.7). The positive predictive value of leukocyturia for predicting IF/TA was 85.7% whereas the negative predictive value was 72.3%. These studies suggest that leukocyturia is a noninvasive and low-cost test to identify IF/TA. An early diagnosis may allow timely interventional measures directed to minimize its impact and improve graft outcom