Effect of rhPDGF-BB on bone turnover during periodontal repair

Purpose : Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of periodontia. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a well-known biomarker of bone turnover, and as such is a potential indicator of osseous metabolic activity. The objective of this study was to evaluate the release of the ICTP into the periodontal wound fluid (WF) following periodontal reconstructive surgery using local delivery of highly purified recombinant human PDGF (rhPDGF)-BB. Methods : Forty-seven human subjects at five treatment centres possessing chronic severe periodontal disease were monitored longitudinally for 24 weeks following PDGF regenerative surgical treatment. Severe periodontal osseous defects were divided into one of three groups and treated at the time of surgery with either: Β -tricalcium phosphate (TCP) osteoconductive scaffold alone (active control), Β -TCP+0.3 mg/ml of rhPDGF-BB, or Β -TCP+1.0 mg/ml of rhPDGF-BB. WF was harvested and analysed for local ICTP levels by radioimmunoassay. Statistical analysis was performed using analysis of variance and an area under the curve analysis (AUC). Results : The 0.3 and 1.0 mg/ml PDGF-BB treatment groups demonstrated increases in the amount of ICTP released locally for up to 6 weeks. There were statistically significant differences at the week 6 time point between Β -TCP carrier alone group versus 0.3 mg/ml PDGF-BB group ( p <0.05) and between Β -TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions ( p <0.03). The AUC analysis revealed no statistical differences amongst groups. Conclusion : This study corroborates the release of ICTP as a measure of active bone turnover following local delivery of PDGF-BB to periodontal osseous defects. The amount of ICTP released from the WF revealed an early increase for all treatment groups. Data from this study suggests that when PDGF-BB is delivered to promote periodontal tissue engineering of tooth-supporting osseous defects, there is a direct effect on ICTP released from the wound.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72239/1/j.1600-051X.2005.00870.x.pd

Measuring service quality and assessing its relationship to contraceptive discontinuation: A prospective cohort study in Pakistan and Uganda

Background: The quality of contraceptive counseling that women receive from their provider can influence their future contraceptive continuation. We examined (1) whether the quality of contraceptive service provision could be measured in a consistent way by using existing tools from 2 large-scale social franchises, and (2) whether facility quality measures based on these tools were consistently associated with contraceptive discontinuation.Methods: We linked existing, routinely collected facility audit data from social franchise clinics in Pakistan and Uganda with client data. Clients were women aged 15-49 who initiated a modern, reversible contraceptive method from a sampled clinic. Consented participants completed an exit interview and were contacted 3, 6, and 12 months later. We collapsed indicators into quality domains using theory-based categorization, created summative quality domain scores, and used Cox proportional hazards models to estimate the relationship between these quality domains and discontinuation while in need of contraception.Results: The 12-month all-modern method discontinuation rate was 12.5% among the 813 enrolled women in Pakistan and 5.1% among the 1,185 women in Uganda. We did not observe similar associations between facility-level quality measures and discontinuation across these 2 settings. In Pakistan, an increase in the structural privacy domain was associated with a 60% lower risk of discontinuation, adjusting for age and baseline method (PP=.005).Conclusions: We were not able to leverage existing, widely used quality measurement tools to create quality domains that were consistently associated with discontinuation in 2 study settings. Given the importance of contraceptive service quality and recent advances in indicator standardization in other areas, we recommend further effort to harmonize and simplify measurement tools to measure and improve contraceptive quality of care for all

Racial/ethnic differences in job loss for women with breast cancer

IntroductionWe examined race/ethnic differences in treatment-related job loss and the financial impact of treatment-related job loss, in a population-based sample of women diagnosed with breast cancer.MethodsThree thousand two hundred fifty two women with non-metastatic breast cancer diagnosed (August 2005-February 2007) within the Los Angeles County and Detroit Metropolitan Surveillance Epidemiology and End Results registries, were identified and asked to complete a survey (mean time from diagnosis = 8.9&nbsp;months). Latina and African American women were over-sampled (n = 2268, eligible response rate 72.1%).ResultsOne thousand one hundred eleven women (69.6%) of working age (&lt;65&nbsp;years) were working for pay at time of diagnosis. Of these women, 10.4% (24.1% Latina, 10.1% African American, 6.9% White, p &lt; 0.001) reported that they lost or quit their job since diagnosis due to breast cancer or its treatment (defined as job loss). Latina women were more likely to experience job loss compared to White women (OR = 2.0, p = 0.013)), independent of sociodemographic factors. There were no significant differences in job loss between African American and White women, independent of sociodemographic factors. Additional adjustments for clinical and treatment factors revealed a significant interaction between race/ethnicity and chemotherapy (p = 0.007). Among women who received chemotherapy, Latina women were more likely to lose their job compared to White women (OR = 3.2, p &lt; 0.001), however, there were no significant differences between Latina and White women among those who did not receive chemotherapy. Women who lost their job were more likely to experience financial strain (e.g. difficulty paying bills 27% vs. 11%, p &lt; 0.001).ConclusionJob loss is a serious consequence of treatment for women with breast cancer. Clinicians and staff need to be aware of aspects of treatment course that place women at higher risk for job loss, especially ethnic minorities receiving chemotherapy

Cross-species complementation reveals conserved functions for EARLY FLOWERING 3 between monocots and dicots

Plant responses to the environment are shaped by external stimuli and internal signaling pathways. In both the model plant Arabidopsis thaliana (Arabidopsis) and crop species, circadian clock factors are critical for growth, flowering, and circadian rhythms. Outside of Arabidopsis, however, little is known about the molecular function of clock gene products. Therefore, we sought to compare the function of Brachypodium distachyon (Brachypodium) and Setaria viridis (Setaria) orthologs of EARLY FLOWERING 3, a key clock gene in Arabidopsis. To identify both cycling genes and putative ELF3 functional orthologs in Setaria, a circadian RNA-seq dataset and online query tool (Diel Explorer) were generated to explore expression profiles of Setaria genes under circadian conditions. The function of ELF3 orthologs from Arabidopsis, Brachypodium, and Setaria was tested for complementation of an elf3 mutation in Arabidopsis. We find that both monocot orthologs were capable of rescuing hypocotyl elongation, flowering time, and arrhythmic clock phenotypes. Using affinity purification and mass spectrometry, our data indicate that BdELF3 and SvELF3 could be integrated into similar complexes in vivo as AtELF3. Thus, we find that, despite 180 million years of separation, BdELF3 and SvELF3 can functionally complement loss of ELF3 at the molecular and physiological level

Socioeconomic inequalities in the rate of stillbirths by cause: a population-based study.

OBJECTIVE: To assess time trends in socioeconomic inequalities in overall and cause-specific stillbirth rates in England. DESIGN: Population-based retrospective study. SETTING: England. PARTICIPANTS: Stillbirths occurring among singleton infants born between 1 January 2000 and 31 December 2007. MAIN OUTCOME MEASURE: Cause-specific stillbirth rate per 10 000 births by deprivation tenth and year of birth. Deprivation measured using the UK index of multiple deprivation at Super Output Area level. METHODS: Poisson regression models were used to estimate the relative deprivation gap (comparing the most and least deprived tenths) in rates of stillbirths (overall and cause-specific). Excess mortality was calculated by applying the rates seen in the least deprived tenth to the entire population at risk. Discussions with our local NHS multicentre ethics committee deemed that this analysis of national non-identifiable data did not require separate ethics approval. RESULTS: There were 44 stillbirths per 10 000 births, with no evidence of a change in rates over time. Rates were twice as high in the most deprived tenth compared with the least (rate ratio (RR) 2.1, 95% CI 2.0 to 2.2) with no evidence of a change over time. There was a significant deprivation gap for all specific causes except mechanical events (RR 1.2, 95% CI 0.9 to 1.5). The widest gap was seen for stillbirths due to antepartum haemorrhages (RR 3.1, 95% CI 2.8 to 3.5). No evidence of a change in the rate of stillbirth or deprivation gap over time was seen for any specific cause. CONCLUSION: A wide deprivation gap exists in stillbirth rates for most causes and is not diminishing. Unexplained antepartum stillbirths accounted for 50% of the deprivation gap, and a better understanding of these stillbirths is necessary to reduce socioeconomic inequalities

Accounting for seasonal patterns in syndromic surveillance data for outbreak detection

BACKGROUND: Syndromic surveillance (SS) can potentially contribute to outbreak detection capability by providing timely, novel data sources. One SS challenge is that some syndrome counts vary with season in a manner that is not identical from year to year. Our goal is to evaluate the impact of inconsistent seasonal effects on performance assessments (false and true positive rates) in the context of detecting anomalous counts in data that exhibit seasonal variation. METHODS: To evaluate the impact of inconsistent seasonal effects, we injected synthetic outbreaks into real data and into data simulated from each of two models fit to the same real data. Using real respiratory syndrome counts collected in an emergency department from 2/1/94–5/31/03, we varied the length of training data from one to eight years, applied a sequential test to the forecast errors arising from each of eight forecasting methods, and evaluated their detection probabilities (DP) on the basis of 1000 injected synthetic outbreaks. We did the same for each of two corresponding simulated data sets. The less realistic, nonhierarchical model's simulated data set assumed that "one season fits all," meaning that each year's seasonal peak has the same onset, duration, and magnitude. The more realistic simulated data set used a hierarchical model to capture violation of the "one season fits all" assumption. RESULTS: This experiment demonstrated optimistic bias in DP estimates for some of the methods when data simulated from the nonhierarchical model was used for DP estimation, thus suggesting that at least for some real data sets and methods, it is not adequate to assume that "one season fits all." CONCLUSION: For the data we analyze, the "one season fits all " assumption is violated, and DP performance claims based on simulated data that assume "one season fits all," for the forecast methods considered, except for moving average methods, tend to be optimistic. Moving average methods based on relatively short amounts of training data are competitive on all three data sets, but are particularly competitive on the real data and on data from the hierarchical model, which are the two data sets that violate the "one season fits all" assumption

Categorising interventions to levels of inpatient care for small and sick newborns: Findings from a global survey.

BACKGROUND: In 2017, 2.5 million newborns died, mainly from prematurity, infections, and intrapartum events. Preventing these deaths requires health systems to provide routine and emergency care at birth, and quality inpatient care for small and sick newborns. Defined levels of emergency obstetric care (EmOC) and standardised measurement of "signal functions" has improved tracking of maternal care in low- and middle-income countries (LMICs). Levels of newborn care, particularly for small and sick newborns, and associated signal functions are still not consistently defined or tracked. METHODS: Between November 2016-November 2017, we conducted an online survey of professionals working in maternal and newborn health. We asked respondents to categorise 18 clinical care interventions that could act as potential signal functions for small and sick newborns to 3 levels of care they thought were appropriate for health systems in LMICs to provide: "routine care at birth", "special care" and "intensive care". We calculated the percentage of respondents that classified each intervention at each level of care and stratified responses to look at variation by respondent characteristics. RESULTS: Six interventions were classified to specific levels by more than 50% of respondents as "routine care at birth," three interventions as "special care" and one as "intensive care". Eight interventions were borderline between these care levels. Responses were more consistent for interventions with relevant WHO clinical care guidelines while more variation in respondents' classification was observed in complex interventions that lack standards or guidelines. Respondents with experience in lower-income settings were more likely to assign a higher level of care for more complex interventions. CONCLUSIONS: Results were consistent with known challenges of scaling up inpatient care in lower-income settings and underline the importance of comprehensive guidelines and standards for inpatient care. Further work is needed to develop a shortlist of newborn signal functions aligned with emergency obstetric care levels to track universal health coverage for mothers and their newborns

Clustered Coding Variants in the Glutamate Receptor Complexes of Individuals with Schizophrenia and Bipolar Disorder

Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic ‘hub’ genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs) was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders