Homeless population

The aim was to derive and analyze a model for numbers of homeless and non-homeless people in a borough, in particular to see how these figures might be affected by different policies regarding housing various categories of people. Most attention was focused on steady populations although the stability of these and possible timescales of dynamic problems were also discussed. The main outcome of this brief study is the identification of the key role played by the constant k_1 - the constant which fixes the speed at which the homeless are rehoused in permanent council property. Reducing this constant, i.e. making the system "fairer" with less priority to accommodating homeless families, appears to have little effect on the sizes of other categories on the waiting list but there is a marked increase in the number of households in temporary accommodation. The model, indicated by the size of its longest time-scale, should be modified to allow for births etc. It could be varied by allowing people to remove themselves from the register or by allowing the rates at which registered and unregistered people become homeless to differ, but these modifications are unlikely to substantially change the main result. The inclusion of movement from the homeless to the general population would have the effect of limiting the numbers in temporary accommodation. However, it is thought this effect is very small so a great reduction in k_1 would be needed for this flow to become significant

Genetic, Maternal and Placental Factors in the Association between Birth Weight and Physical Fitness: A Longitudinal Twin Study

Background Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations. Design Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey. Results We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, P = 0.02), arm pull (b = 1.85 kg per kg birth weight P = 0.03) and flamingo balance (b = −1.82 attempts to stand one minute per kg birth weight, P = 0.03). Maximum oxygen uptake appeared to have a U-shaped association with birth weight (the smallest and largest children had the lowest uptake, P = 0.01), but this association was no longer significant after adjustment for parental BMI. Using the individual twin’s deviation from his own twin pair’s average birth weight, we found positive associations between birth weight and adolescent vertical jump (b = 3.49, P = 0.0007) and arm pull (b = 3.44, P = 0.02). Δ scores were calculated within the twin pairs as first born twin minus second born twin. Δ birth weight was associated with Δ vertical jump within MZ twin pairs only (b = 2.63, P = 0.009), which indicates importance of placental factors. Conclusions We found evidence for an association between adolescent physical performance (strength, balance and possibly peak oxygen uptake) and birth weight. The associations with vertical jump and arm pull were likely based on individual, more specifically placental (in the case of vertical jump) factors. Our results should be viewed as hypothesis-generating and need confirmation, but potentially support preventive strategies to optimize birth weight, for example via placental function, to target later fitness and health

Genetic predisposition score predicts the increases of knee strength and muscle mass after one-year exercise in healthy elderly

This study aims to identify a genetic predisposition score from a set of candidate gene variants that predicts the response to a one-year exercise intervention. 200 participants (aged 60–83 years) were randomly assigned to a fitness (FIT), whole-body vibration (WBV) and control group. Participants in the exercise (FIT and WBV) groups performed a one-year intervention program. Whole-body skeletal muscle mass (SMM) and isometric knee extension strength (PTIM60) were measured before and after the intervention. A set of 170 muscle-related single nucleotide polymorphisms (SNPs) were genotyped. Stepwise regression analysis was applied to select significantly contributing SNPs for baseline and relative change parameters. A data-driven genetic predisposition score (GPS) was calculated by adding up predisposing alleles for each of the phenotypes. GPS was calculated based on 4 to 8 SNPs which were significantly related to the corresponding phenotypes. These SNPs belong to genes that are involved in myoblast differentiation, muscle and bone growth, myofiber contraction, cytokines and DNA methylation. GPS was related to baseline PTIM60and relative changes of SMM and PTIM60in the exercise groups, explaining the variance of the corresponding parameter by 3.2%, 14% and 27%, respectively. Adding one increasing allele in the GPS increased baseline PTIM60by 4.73 Nm, and exercise-induced relative changes of SMM and PTIM60by 1.78% and 3.86% respectively. The identified genetic predisposition scores were positively related to baseline knee extension strength and muscle adaptations to exercise in healthy elderly. These findings provide supportive genetic explanations for high and low responders in exercise-induced muscle adaptations

The VASCERN PPL working group patient pathway for primary and paediatric lymphoedema.

Lymphoedema is caused by an imbalance between fluid production and transport by the lymphatic system. This imbalance can be either caused by reduced transport capacity of the lymphatic system or too much fluid production and leads to swelling associated with tissue changes (skin thickening, fat deposition). Its main common complication is the increased risk of developing cellulitis/erysipelas in the affected area, which can worsen the lymphatic function and can be the cause of raised morbidity of the patient if not treated correctly/urgently. The term primary lymphoedema covers a group of rare conditions caused by abnormal functioning and/or development of the lymphatic system. It covers a highly heterogeneous group of conditions. An accurate diagnosis of primary lymphoedema is crucial for the implementation of an optimal treatment plan and management, as well as to reduce the risk of worsening. Patient care is diverse across Europe, and national specialised centres and networks are not available everywhere. The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) gathers the best expertise in Europe and provide accessible cross-border healthcare to patients with rare vascular diseases. There are six different working groups in VASCERN, which focus on arterial diseases, hereditary haemorrhagic telangiectasia, neurovascular diseases, lymphoedema and vascular anomalies. The working group Paediatric and Primary Lymphedema (PPL WG) gathers and shares knowledge and expertise in the diagnosis and management of adults and children with primary and paediatric lymphoedema. The members of PPL WG have worked together to produce this opinion statement reflecting strategies on how to approach patients with primary and paediatric lymphoedema. The objective of this patient pathway is to improve patient care by reducing the time to diagnosis, define the best management and follow-up strategies and avoid overuse of resources. Therefore, the patient pathway describes the clinical evaluation and investigations that lead to a clinical diagnosis, the genetic testing, differential diagnosis, the management and treatment options and the patient follow up at expert and local centres. Also, the importance of the patient group participation in the PPL WG is discussed

Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants

<p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme (ACE) gene contains a polymorphism, consisting of either the presence (I) or absence (D) of a 287 base pair fragment. Deletion (D) is associated with increased circulating ACE (cACE) activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pi_max). Pressure-time index of the respiratory muscles (PTImus) is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles.</p> <p>The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population.</p> <p>Methods</p> <p>Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pi_mean/Pi_max) × (Ti/Ttot), where Pi_meanwas the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P_0.1), Pi_maxwas the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pi_maxwas the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort.</p> <p>Results</p> <p>A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pi_maxand inversely related to PTImus. No association between ACE genotypes and Pdi_maxmeasurements was found.</p> <p>Conclusions</p> <p>These results suggest that a relation in cACE activity and respiratory muscle function may exist in infants. In addition, an association between ACE genotypes and cACE activity, but not respiratory muscle strength, was demonstrated.</p

Tumor-Shed PGE2 Impairs IL2Rγc-Signaling to Inhibit CD4+ T Cell Survival: Regulation by Theaflavins

BACKGROUND:Many tumors are associated with decreased cellular immunity and elevated levels of prostaglandin E2 (PGE2), a known inhibitor of CD4+ T cell activation and inducer of type-2 cytokine bias. However, the role of this immunomodulator in the survival of T helper cells remained unclear. Since CD4+ T cells play critical roles in cell-mediated immunity, detail knowledge of the effect tumor-derived PGE2 might have on CD4+ T cell survival and the underlying mechanism may, therefore, help to overcome the overall immune deviation in cancer. METHODOLOGY/PRINCIPAL FINDINGS:By culturing purified human peripheral CD4+ T cells or Jurkat cells with spent media of theaflavin- or celecoxib-pre-treated MCF-7 cells, we show that tumor-shed PGE2 severely impairs interleukin 2 receptor gammac (IL2Rgammac)-mediated survival signaling in CD4+ T cells. Indeed, tumor-shed PGE2 down-regulates IL2Rgammac expression, reduces phosphorylation as well as activation of Janus kinase 3 (Jak-3)/signal transducer and activator of transcription 5 (Stat-5) and decreases Bcl-2/Bax ratio thereby leading to activation of intrinsic apoptotic pathway. Constitutively active Stat-5A (Stat-5A1 6) over-expression efficiently elevates Bcl-2 levels in CD4+ T cells and protects them from tumor-induced death while dominant-negative Stat-5A over-expression fails to do so, indicating the importance of Stat-5A-signaling in CD4+ T cell survival. Further support towards the involvement of PGE2 comes from the results that (a) purified synthetic PGE2 induces CD4+ T cell apoptosis, and (b) when knocked out by small interfering RNA, cyclooxygenase-2 (Cox-2)-defective tumor cells fail to initiate death. Interestingly, the entire phenomena could be reverted back by theaflavins that restore cytokine-dependent IL2Rgammac/Jak-3/Stat-5A signaling in CD4+ T cells thereby protecting them from tumor-shed PGE2-induced apoptosis. CONCLUSIONS/SIGNIFICANCE:These data strongly suggest that tumor-shed PGE2 is an important factor leading to CD4+ T cell apoptosis during cancer and raise the possibility that theaflavins may have the potential as an effective immunorestorer in cancer-bearer

Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-β mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or α-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)–mediated eukaryotic initiation factor (eIF)2α phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2α accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2α phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2α phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts

Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966

Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0-20 years. Twenty-six of the 48 variants tested associated with adult height (p&lt;0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p&lt;0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth

The Dynamics of T-Cell Receptor Repertoire Diversity Following Thymus Transplantation for DiGeorge Anomaly

T cell populations are regulated both by signals specific to the T-cell receptor (TCR) and by signals and resources, such as cytokines and space, that act independently of TCR specificity. Although it has been demonstrated that disruption of either of these pathways has a profound effect on T-cell development, we do not yet have an understanding of the dynamical interactions of these pathways in their joint shaping of the T cell repertoire. Complete DiGeorge Anomaly is a developmental abnormality that results in the failure of the thymus to develop, absence of T cells, and profound immune deficiency. After receiving thymic tissue grafts, patients suffering from DiGeorge anomaly develop T cells derived from their own precursors but matured in the donor tissue. We followed three DiGeorge patients after thymus transplantation to utilize the remarkable opportunity these subjects provide to elucidate human T-cell developmental regulation. Our goal is the determination of the respective roles of TCR-specific vs. TCR-nonspecific regulatory signals in the growth of these emerging T-cell populations. During the course of the study, we measured peripheral blood T-cell concentrations, TCRβ V gene-segment usage and CDR3-length spectratypes over two years or more for each of the subjects. We find, through statistical analysis based on a novel stochastic population-dynamic T-cell model, that the carrying capacity corresponding to TCR-specific resources is approximately 1000-fold larger than that of TCR-nonspecific resources, implying that the size of the peripheral T-cell pool at steady state is determined almost entirely by TCR-nonspecific mechanisms. Nevertheless, the diversity of the TCR repertoire depends crucially on TCR-specific regulation. The estimated strength of this TCR-specific regulation is sufficient to ensure rapid establishment of TCR repertoire diversity in the early phase of T cell population growth, and to maintain TCR repertoire diversity in the face of substantial clonal expansion-induced perturbation from the steady state