Volumetric Response and Survival of Patients With Bulky IDH-Mutated Grade 3 Glioma Managed With FET-FDG-Guided Integrated Boost IMRT.

AIMS: Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes. RESULTS: The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm3 compared to 186.2cm3 for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm3, 8.0cm3 and 5.3cm3 at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm3, 29.1cm3 and 26.3cm3. The median T1 and T2 volume reductions were 77% (q1-3: 57-92%) and 78% (q1-3: 60-85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0-1, 45% were employed at prior capacity and 28% were working with impairment. CONCLUSION: Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour.

The sexuality of women with cervical cancer undergoing definitive radiotherapy in Ghana.

INTRODUCTION: The purpose of this study was to assess the sexuality of cervical cancer patients undergoing radiotherapy at a major cancer treatment center in Ghana. This is an area of interest as globally; cervical cancer kills approximately 342,000 people per annum with an estimated number of 604,000 new cases in 2020. Acknowledging the World Health Organization's definition of sexual health as a state of physical, mental and social well-being in relation to sexuality, this paper sheds light on how these dimensions affect the quality of life of cervical cancer patients. METHODS: This was a longitudinal study, which assessed the impact of radiotherapy on the sexuality of both premenopausal and postmenopausal cervical cancer patients presenting for primary treatment with chemoradiation from April to July, 2021 at a major cancer treatment centre in Ghana. The Female Sexual Function Index and Body Image Scale questionnaires were respectively used to evaluate the sexual functions scores among the cervical cancer patients, and to assess the impact of the treatment on their body image. MATLAB software was used for data analysis. RESULTS: Most of the cervical cancer patients sampled were postmenopausal (57 %). About 79 % premenopausal and 96 % postmenopausal cervical cancer patients were sexually inactive during radiotherapy (day 15). Also, 48 % premenopausal and 24 % postmenopausal patients were very dissatisfied with their bodies at the onset of treatment. The frequency of orgasm in cervical cancer patients declined after treatment causing a deterioration in their sexual function. The patients' sexuality was influenced by age and menopausal status. The decreased sexual desire of the patients resulted in emotional distancing from their partners, which invariably induced changes in their partners' level of sexual interest. This study established significant differences between premenopausal and postmenopausal cervical cancer patients who were generally very dissatisfied with their sexual relationships with their partners on day 1 (p = 0.02) and on day 15 (p = 0.00) of treatment. CONCLUSION: The majority of patients who presented for treatment for cervical cancer in this study were postmenopausal. Their interest in sexual activity was more influenced by their menopausal status than their antineoplastic treatment. This study indicates that cervical cancer patients are more likely to develop sexual health problems which could substantially worsen over the course of their treatment and beyond. IMPLICATION FOR PRACTICE: The study will contribute within the oncology team by assisting personnel in putting in place measures that will guide the treatment of cervical cancer patients and improve quality of care.

Using network analysis to detect associations between suspected painful health conditions and behaviour in dogs.

Pain associated with chronic health conditions in non-human animals is an important animal welfare issue. To identify animals in pain and develop an understanding of the mechanisms by which pain affects behaviour, it is therefore important to establish the direct behavioural effects of painful health conditions. We reanalyse data from a cross-sectional survey that considered the presence or absence of a painful condition in dogs and quantified their affective predispositions using the Positive and Negative Activation Scale (PANAS). By applying ideas from network theory, we conceptualise pain as a stressor that exerts direct effects on a network of interacting behavioural variables, and subsequently estimated a network model of conditional dependence relations. Painful health conditions were positively conditionally associated with age (posterior mean partial correlation, ρ = 0.34; standard deviation [SD]=0.05), and negatively conditionally associated with the item 'your dog is full of energy' (ρ = -0.14; SD=0.06). In turn, the energy item was conditionally associated with other PANAS items which were marginally associated with pain, such as items representing ease of excitability and persistence in play. This suggests these marginal effects might be indirectly mediated via the energy item. Further, utilising the posterior predictive distribution we estimated that the median conditional probability (95% credible interval) of a painful health condition given an answer of 'strongly agree' on the energy item was 0.08 (0.05, 0.11), which increased to 0.32 (0.09, 0.58), given a response of 'strongly disagree'. This provides a potentially clinically useful interpretation of the conditional dependencies detected in the network.

An ethological analysis of close-contact inter-cat interactions determining if cats are playing, fighting, or something in between.

Intraspecific social interactions in domestic cats are often categorised as affiliative or agonistic. However, public or professional assessment of encounters can have difficulty distinguishing rough-and-tumble play from true agonism. One possible issue is the potential occurrence of elements of both, play and agonism, within inter-cat play, for example when one cat wants to terminate a bout of play but the other seeks to continue the interaction, which subsequently may provoke more overt agonistic behaviour. To test this hypothesis, we conducted behavioural observations of 105 unique dyadic interactions of domestic cats (N = 210) captured on videos collected from owners and YouTube. We assessed cats for the frequency and duration of six behavioural elements. The dataset was reduced using PCA with a varimax rotation and factor scores were used to classify the population using hierarchical cluster analysis. To validate the identified clusters, the average scores of the constituent factors were compared and the data on interactions were labelled by four cat behaviour experts as "playful", "intermediate" or "agonistic". In addition, to evaluate properties of expert-labelled categories we used linear discriminant analysis followed by an ordinal regression. The results showed considerable convergent validity in factor distributions between clusters and expert-labelled groups: reciprocal wrestling was most closely associated with a group of playfully interacting cats, while vocalisation and chasing were associated with the agonistic group. The intermediate group, while having characteristics of both, was more closely related to the playful group than the agonistic group, with prolonged exchanges of interactive behaviours being a predominant feature. Thus, our findings support the suggestion of there being an intermediate category between mutual social play and agonism. This might escalate into a fully agonistic encounter, but does not necessarily reflect a break down in their social relationship but rather a short-term disagreement in social priorities.

Composite 3D printing of biomimetic human teeth.

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces.

Evaluating the accuracy of facial expressions as emotion indicators across contexts in dogs.

Facial expressions potentially serve as indicators of animal emotions if they are consistently present across situations that (likely) elicit the same emotional state. In a previous study, we used the Dog Facial Action Coding System (DogFACS) to identify facial expressions in dogs associated with conditions presumably eliciting positive anticipation (expectation of a food reward) and frustration (prevention of access to the food). Our first aim here was to identify facial expressions of positive anticipation and frustration in dogs that are context-independent (and thus have potential as emotion indicators) and to distinguish them from expressions that are reward-specific (and thus might relate to a motivational state associated with the expected reward). Therefore, we tested a new sample of 28 dogs with a similar set-up designed to induce positive anticipation (positive condition) and frustration (negative condition) in two reward contexts: food and toys. The previous results were replicated: Ears adductor was associated with the positive condition and Ears flattener, Blink, Lips part, Jaw drop, and Nose lick with the negative condition. Four additional facial actions were also more common in the negative condition. All actions except the Upper lip raiser were independent of reward type. Our second aim was to assess basic measures of diagnostic accuracy for the potential emotion indicators. Ears flattener and Ears downward had relatively high sensitivity but low specificity, whereas the opposite was the case for the other negative correlates. Ears adductor had excellent specificity but low sensitivity. If the identified facial expressions were to be used individually as diagnostic indicators, none would allow consistent correct classifications of the associated emotion. Diagnostic accuracy measures are an essential feature for validity assessments of potential indicators of animal emotion.

The plate-to-rod transition in trabecular bone loss is elusive.

Changes in trabecular micro-architecture are key to our understanding of osteoporosis. Previous work focusing on structure model index (SMI) measurements have concluded that disease progression entails a shift from plates to rods in trabecular bone, but SMI is heavily biased by bone volume fraction. As an alternative to SMI, we proposed the ellipsoid factor (EF) as a continuous measure of local trabecular shape between plate-like and rod-like extremes. We investigated the relationship between EF distributions, SMI and bone volume fraction of the trabecular geometry in a murine model of disuse osteoporosis as well as from human vertebrae of differing bone volume fraction. We observed a moderate shift in EF median (at later disease stages in mouse tibia) and EF mode (in the vertebral samples with low bone volume fraction) towards a more rod-like geometry, but not in EF maximum and minimum. These results support the notion that the plate to rod transition does not coincide with the onset of bone loss and is considerably more moderate, when it does occur, than SMI suggests. A variety of local shapes not straightforward to categorize as rod or plate exist in all our trabecular bone samples.

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.

BACKGROUND: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC. PATIENTS AND METHODS: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant. Overall survival (OS) in the PIK3CA-mutant cohort was evaluated by Kaplan-Meier methodology and a one-sided stratified log-rank test was carried out with an O'Brien-Fleming efficacy boundary of P ≤ 0.0161. RESULTS: In the PIK3CA-mutated cohort (n = 341), median OS [95% confidence interval (CI)] was 39.3 months (34.1-44.9) for alpelisib-fulvestrant and 31.4 months (26.8-41.3) for placebo-fulvestrant [hazard ratio (HR) = 0.86 (95% CI, 0.64-1.15; P = 0.15)]. OS results did not cross the prespecified efficacy boundary. Median OS (95% CI) in patients with lung and/or liver metastases was 37.2 months (28.7-43.6) and 22.8 months (19.0-26.8) in the alpelisib-fulvestrant and placebo-fulvestrant arms, respectively [HR = 0.68 (0.46-1.00)]. Median times to chemotherapy (95% CI) for the alpelisib-fulvestrant and placebo-fulvestrant arms were 23.3 months (15.2-28.4) and 14.8 months (10.5-22.6), respectively [HR = 0.72 (0.54-0.95)]. No new safety signals were observed with longer follow-up. CONCLUSIONS: Although the analysis did not cross the prespecified boundary for statistical significance, there was a 7.9-month numeric improvement in median OS when alpelisib was added to fulvestrant treatment of patients with PIK3CA-mutated, HR+, HER2- ABC. Overall, these results further support the statistically significant prolongation of PFS observed with alpelisib plus fulvestrant in this population, which has a poor prognosis due to a PIK3CA mutation. CLINICALTRIALS. GOV ID: NCT02437318.

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

BACKGROUND: Alpelisib (α-selective phosphatidylinositol 3-kinase inhibitor) plus fulvestrant is approved in multiple countries for men and postmenopausal women with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib's safety profile should inform adverse event (AE) management and enhance patient care. PATIENTS AND METHODS: AEs in the phase III SOLAR-1 trial were assessed in patients with and without PIK3CA mutations. The impact of protocol-specified AE-management recommendations was evaluated, including an amendment to optimize hyperglycemia and rash management. RESULTS: Patients were randomly assigned to receive fulvestrant plus alpelisib (n = 284) or placebo (n = 287). The most common grade 3/4 AEs with alpelisib were hyperglycemia (grade 3, 32.7%; grade 4, 3.9%), rash (grade 3, 9.9%), and diarrhea (grade 3, 6.7%). Median time to onset of grade ≥3 toxicity was 15 days (hyperglycemia, based on fasting plasma glucose), 13 days (rash), and 139 days (diarrhea). Metformin alone or in combination with other antidiabetic agents was used by most patients (87.1%) with hyperglycemia. Preventive anti-rash medication resulted in lower incidence (any grade, 26.7% versus 64.1%) and severity of rash (grade 3, 11.6% versus 22.7%) versus no preventative medication. Discontinuations due to grade ≥3 AEs were lower following more-detailed AE management guidelines (7.9% versus 18.1% previously). Patients with PIK3CA mutations had a median alpelisib dose intensity of 248 mg/day. Median progression-free survival with alpelisib was 12.5 and 9.6 months for alpelisib dose intensities of ≥248 mg/day and <248 mg/day, respectively, compared with 5.8 months with placebo. CONCLUSIONS: Hyperglycemia and rash occurred early during alpelisib treatment, while diarrhea occurred at a later time point. Early identification, prevention, and intervention, including concomitant medications and alpelisib dose modifications, resulted in less severe toxicities. Reductions in treatment discontinuations and improved progression-free survival at higher alpelisib dose intensities support the need for optimal AE management. CLINICALTRIALS. GOV ID: NCT02437318.

Nanostrain sensitivity in a wire torsion experiment.

The feasibility of a thin-wire torsion stress-strain experiment with nanostrain sensitivity is demonstrated. A gauge length of 50 m was made possible by using The Monument, London, thereby restoring it to its original purpose as a scientific instrument. A wire of 150 µm diameter was studied using the load-unload method, and data were recorded in the elastic regime and through the elastic-plastic transition. Analysis of this preliminary experiment suggested some necessary improvements to the equipment and methods. Progress towards definitive experiments is described together with difficulties still to be overcome.

Towards a fuller assessment of the economic benefits of reducing air pollution from fossil fuel combustion: Per-case monetary estimates for children's health outcomes.

BACKGROUND: Impacts on children's health are under-represented in benefits assessments of policies related to ambient air quality and climate change. To complement our previous compilation of concentration-response (C-R) functions for a number of children's health outcomes associated with air pollution, we provide per-case monetary estimates of the same health outcomes. OBJECTIVES: Our goal was to establish per-case monetary estimates for a suite of prevalent children's health outcomes (preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction) that can be incorporated into benefits assessments of air pollution regulations and climate change mitigation policies. METHODS: We conducted a systematic review of the literature published between January 1, 2000 and June 30, 2018 to identify relevant economic costs for these six adverse health outcomes in children. We restricted our literature search to studies published in the U.S., with a supplemental consideration of studies from the U.K. and prioritized literature reviews with summary cost estimates and papers that provided lifetime cost of illness estimates. RESULTS: Our literature search and evaluation process reviewed 1065 papers and identified 12 most relevant papers on per-case monetary estimates for preterm birth, low birth weight, asthma, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Details are presented in full. We separately identified estimates of the lost lifetime earnings associated with the loss of a single IQ point. The final per-case cost estimates for each outcome were selected based on the most robust evidence. These estimates range from $23,573 for childhood asthma not persisting into adulthood to $3,109,096 for a case of autism with a concurrent intellectual disability. CONCLUSION: To our knowledge, this is the first time that the child-specific health outcomes of preterm birth, low birth weight, asthma, autism spectrum disorder, attention-deficit/hyperactivity disorder, and IQ reduction have been systematically valued and presented in one place. This is an important addition to the body of health-related valuation literature as these outcomes have substantial economic costs that are not considered in most assessments of the benefits of air pollution and climate mitigation policies. In general, however, the available per-case estimates presented here did not incorporate the broad societal and long-term costs and are likely underestimates. Although our context has been air pollution and climate policies, the per-case monetary estimates presented here can be applied to other environmental exposures. Fuller assessments of health benefits to children and their corresponding economic gains will improve decision-making on environmental policy.

Vancomycin area under the curve to minimum inhibitory concentration ratio predicting clinical outcome: a systematic review and meta-analysis with pooled sensitivity and specificity.

BACKGROUND: Vancomycin is a first-line antibiotic for methicillin-resistant Staphylococcus aureus infections or other Gram-positive infections. The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter. How well clinical efficacy is predicted by this measure has not been established. OBJECTIVE: Determine the test performance characteristics (TPC) of AUC:MIC of vancomycin for prediction of positive outcome. DATA SOURCES: PubMed and Ovid Medline (1946 to 2018) and EMBASE (1974 to 2018). Study Eligibility Criteria and Participants: Studies of patients treated with vancomycin for any type of infection in peer reviewed publications. All patient populations were included. INTERVENTIONS: Vancomycin AUC:MIC or AUC was related to patient clinical outcome. METHODS: Searches of medical databases using relevant terms were performed. Screening, study reviewing, data extracting and assessing data quality was performed independently by two reviewers. Studies were stratified by type of primary outcome for calculation of pooled sensitivity, specificity and construction of hierarchical summary receiver operating characteristic (HSROC) curves. RESULTS: Nineteen studies including 1699 patients were meta-analysed. Pooled sensitivity and specificity were 0.77 (95% CI 0.67-0.84) and 0.62 (95% CI 0.53-0.71) respectively for the seven studies with primary outcome of mortality and 0.65 (95% CI 0.53-0.75), 0.58 (95% CI 0.48-0.67) for studies with composite or clinical cure outcome (n = 12). HSROC curves suggested considerable heterogeneity. An additional 11 studies were described but could not be included for meta-analysis because data were not available. The majority of these studies (9/11) failed to demonstrate a relationship between AUC:MIC and positive clinical outcome. CONCLUSIONS: Vancomycin AUC:MIC performance was modest and inconsistent. Analysis was limited by studies without sufficient data; therefore, meta-analytic results may overestimate TPC values. Given this, as well as the lack of standardization of methods, widespread adoption of AUC:MIC as the preferred vancomycin monitoring parameter may be premature.

Active site rearrangement and structural divergence in prokaryotic respiratory oxidases.

Cytochrome bd-type quinol oxidases catalyze the reduction of molecular oxygen to water in the respiratory chain of many human-pathogenic bacteria. They are structurally unrelated to mitochondrial cytochrome c oxidases and are therefore a prime target for the development of antimicrobial drugs. We determined the structure of the Escherichia coli cytochrome bd-I oxidase by single-particle cryo-electron microscopy to a resolution of 2.7 angstroms. Our structure contains a previously unknown accessory subunit CydH, the L-subfamily-specific Q-loop domain, a structural ubiquinone-8 cofactor, an active-site density interpreted as dioxygen, distinct water-filled proton channels, and an oxygen-conducting pathway. Comparison with another cytochrome bd oxidase reveals structural divergence in the family, including rearrangement of high-spin hemes and conformational adaption of a transmembrane helix to generate a distinct oxygen-binding site.

Projecting Changes in Expected Annual Damages From Riverine Flooding in the United States.

Inland flood risk in the United States is most often conveyed through maps of 1% annual exceedance probability (AEP) or "100-year" floodplains. However, monetary damages from flooding arise from a full distribution of events, including floods both larger and smaller than the 1% AEP event. Furthermore, floodplains are not static, since both the frequency and magnitude of flooding are likely to change in a warming climate. We explored the implications of a changing frequency and magnitude of flooding across a wide spectrum of flood events, using a sample of 376 watersheds in the United States where floodplains from multiple recurrence intervals have been mapped. Using an inventory of assets within these mapped floodplains, we first calculated expected annual damages (EADs) from flooding in each watershed under baseline climate conditions. We find that the EAD is typically a factor of 5-7 higher than the expected damages from 100-year events alone and that much of these damages are attributable to floods smaller than the 1% AEP event. The EAD from flooding typically increases by 25-50% under a 1 °C warming scenario and in most regions more than double under a 3 °C warming scenario. Further increases in EAD are not as pronounced beyond 3 °C warming, suggesting that most of the projected increases in flood damages will have already occurred, for most regions of the country, by that time. Adaptations that protect against today's 100-year flood will have increasing benefits in a warmer climate by also protecting against more frequent, smaller events.

Towards a fuller assessment of benefits to children's health of reducing air pollution and mitigating climate change due to fossil fuel combustion.

BACKGROUND: Fossil fuel combustion by-products, including particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAH), nitrogen dioxide (NO2) and carbon dioxide (CO2), are a significant threat to children's health and equality. Various policies to reduce emissions have been implemented to reduce air pollution and mitigate climate change, with sizeable estimated health and economic benefits. However, only a few adverse outcomes in children have been considered, resulting in an undercounting of the benefits to this vulnerable population. OBJECTIVES: Our goal was to expand the suite of child health outcomes addressed by programs to assess health and economic benefits, such as the Environmental Protection Agency (EPA) Benefits Mapping and Analysis Program (BenMAP), by identifying concentration-response (C-R) functions for six outcomes related to PM2.5, NO2, PAH, and/or PM10: preterm birth (PTB), low birthweight (LBW), autism, attention deficit hyperactivity disorder, IQ reduction, and the development of childhood asthma. METHODS: We conducted a systematic review of the literature published between January 1, 2000 and April 30, 2018 to identify relevant peer-reviewed case-control and cohort studies and meta-analyses. In some cases meta-analyses were available that provided reliable C-R functions and we assessed their consistency with subsequent studies. Otherwise, we reviewed all eligible studies published between our search dates. RESULTS: For each pollutant and health outcome, we present the characteristics of each selected study. We distinguish between C-R functions for endpoints having a causal or likely relationship (PTB, LBW, autism, asthma development) with the pollutants for incorporation into primary analyses and endpoints having a suggestive causal relationship with the pollutants (IQ reduction, ADHD) for secondary analyses. CONCLUSION: We have identified C-R functions for a number of adverse health outcomes in children associated with air pollutants largely from fossil fuel combustion. Their incorporation into expanded assessments of health benefits of clean air and climate mitigation policies will provide an important incentive for preventive action.

Comparison of the Efficacy of Different Fluoride Varnishes on Dentin Remineralization During a Critical pH Exposure Using Quantitative X-Ray Microtomography.

OBJECTIVES:: The objective of this in vitro study was to quantify the amount of mineral change in demineralized dentin at pH 5.5 after the application of dental varnishes containing fluoride with casein phosphopeptide-amorphous calcium phosphate, fluoride and bioglass, or fluoride alone. METHODS AND MATERIALS:: A total of 12 extracted human sound mandibular premolar root samples were coated with an acid-resistant varnish, leaving a 2 × 3 mm window at the outer root surface. These root specimens were then randomly divided into four groups and separately subjected to the demineralizing cycle at a pH of 4.8 for five days to create artificial caries-like lesions in dentin. Subsequently, each sample was imaged using quantitative x-ray microtomography (XMT) at a 15-µm voxel size. Each test group then received one of the following treatments: dental varnish containing casein phosphopeptide-amorphous calcium phosphate and fluoride (CPP-ACP, MI varnish, GC Europe), bioglass and fluoride (BGA, Experimental, Dentsply Sirona), or fluoride alone (NUPRO, Dentsply Sirona), as well as a control group, which received no treatment. These samples were kept in deionized water for 12 hours. The thin layer of varnish was then removed. All samples including the nonvarnish group were subjected to the second demineralizing cycle at pH 5.5 for five days. The final XMT imaging was then carried out following the second demineralizing cycle. XMT scan was also carried out to varnish samples at 25 µm voxel size. The change in mineral concentration in the demineralized teeth was assessed using both qualitative and quantitative image analysis. RESULTS:: There was an increase in radiopacity in the subtracted images of all varnish groups; a significant increase in mineral content, 12% for the CPP-ACP and fluoride ( p≤0.05 and p≤0.001), 25% BGA ( p≤0.001), and 104% fluoride alone varnish ( p≤0.001). There was an increase in the size of radiolucency in the lesion area with a significant decrease in mineral content in the nonvarnish group, 10% ( p≤0.05 and p≤0.001). CONCLUSIONS:: There was encouraging evidence of a remineralization effect following the application of dental varnish on dentin and also an observed resistance to demineralization during the acidic challenge in all cases. However, a dental varnish containing fluoride alone appeared to have a much greater effect on dentin remineralization when compared with CPP-ACP with fluoride and bioglass with fluoride.