Physics-informed machine learning: case studies for weather and climate modelling.

Machine learning (ML) provides novel and powerful ways of accurately and efficiently recognizing complex patterns, emulating nonlinear dynamics, and predicting the spatio-temporal evolution of weather and climate processes. Off-the-shelf ML models, however, do not necessarily obey the fundamental governing laws of physical systems, nor do they generalize well to scenarios on which they have not been trained. We survey systematic approaches to incorporating physics and domain knowledge into ML models and distill these approaches into broad categories. Through 10 case studies, we show how these approaches have been used successfully for emulating, downscaling, and forecasting weather and climate processes. The accomplishments of these studies include greater physical consistency, reduced training time, improved data efficiency, and better generalization. Finally, we synthesize the lessons learned and identify scientific, diagnostic, computational, and resource challenges for developing truly robust and reliable physics-informed ML models for weather and climate processes. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Human papillomavirus and oral cancer: a primer for dental public health professionals.

UNLABELLED: There is strong evidence for causal association between human papillomavirus (HPV) and cervical cancer, evidence of association of HPV and oropharyngeal cancer is beginning to mount. OBJECTIVES: To review the HPV-oral cancer literature for a comprehensive assessment of the issues involved. METHODS: Literature search conducted using PubMed, Google Scholar and Google search engine. RESULTS: Both available HPV vaccines are efficacious and safe although expensive. Policy for mandatory HPV vaccination for cervical prevention is mired in political issues stemming from negative cost-effectiveness balance. Dental professionals are not ready to discuss the role of HPV vaccine in cancer prevention. This review discusses the impact of HPV on cervical cancer, transmission of HPV among humans, impact of HPV in oral health, and its plausible role in oral and oropharyngeal cancer, prevention of HPV transmission, available vaccines against HPV, testing, cost, policy and use of HPV vaccines internationally and dentists readiness related to HPV associated health communication. CONCLUSIONS: Given the mounting literature on the association between HPV and oropharyngeal cancer, the dental community must be prepared to answer patients' HPV-related questions and to educate patients about the role of HPV as a risk factor for oral and oropharyngeal cancers.

Determinants and trends in dental expenditures in the adult US population: Medical Expenditure Panel Survey 1996-2006.

OBJECTIVES: To estimate dental expenditures in 2006, to analyse dental expenditures by potential explanatory factors for 2006 and to explore trends in dental expenditures from 1996-2006. METHODS: Medical Expenditure Panel Survey (MEPS) data were used. T-tests and analysis of variance were used to test for significance. Multivariable linear regression analysis was conducted to identify independent predictors of dental expenditures. The trend analysis was conducted for the 11-year period, 1996-2006, on adults aged 25 years and older. Expenditures were inflation adjusted to 2006 dollars using the annual average Consumer Price Index. Data were analysed using the MEPS query tool and SASv9.2. RESULTS: In the 2006 MEPS sample, 8,001 adults had dental expenditures and when weighted represented about 93 million non-institutionalised adult US civilians. The mean dental expenditures for this weighted sample were $611 (sd 1,309), median $233 (inter-quartile range 466). As expected, in 2006, dental expenditures increased with age. Those adults who reported their self-perceived health status as 'excellent' were observed to have lowest dental expenditures in this category. After adjusting for other variables in the multivariable linear regression analysis of dental expenditures, age, race/ethnicity, income, geographic location, perceived health status and dental insurance coverage remained significant. CONCLUSION: Dental expenditures for 2006 were $611 (mean) and $233 (median). The time-trend showed substantial but non-uniform annual changes in real dental expenditures between 1996 and 2006.

Spherical mesh adaptive direct search for separating quasi-uncorrelated sources by range-based independent component analysis.

It is seemingly paradoxical to the classical definition of the independent component analysis (ICA), that in reality, the true sources are often not strictly uncorrelated. With this in mind, this letter concerns a framework to extract quasi-uncorrelated sources with finite supports by optimizing a range-based contrast function under unit-norm constraints (to handle the inherent scaling indeterminacy of ICA) but without orthogonality constraints. Albeit the appealing contrast properties of the range-based function (e.g., the absence of mixing local optima), the function is not differentiable everywhere. Unfortunately, there is a dearth of literature on derivative-free optimizers that effectively handle such a nonsmooth yet promising contrast function. This is the compelling reason for the design of a nonsmooth optimization algorithm on a manifold of matrices having unit-norm columns with the following objectives: to ascertain convergence to a Clarke stationary point of the contrast function and adhere to the necessary unit-norm constraints more naturally. The proposed nonsmooth optimization algorithm crucially relies on the design and analysis of an extension of the mesh adaptive direct search (MADS) method to handle locally Lipschitz objective functions defined on the sphere. The applicability of the algorithm in the ICA domain is demonstrated with simulations involving natural, face, aerial, and texture images.

Oral health care services utilisation in the adult US population: Medical Expenditure Panel Survey 2006.

OBJECTIVES: To estimate the proportion of dental visits and to explore determinants of oral health care service (OHCS) utilisation among US civilian non-institutionalised adults. METHODS: Cross-sectional data from the 2006 Medical Expenditure Panel Survey (MEPS) were used to analyse adults' self-reported dental visits across potential risk factors (n = 22,721). MEPS uses a complex sample design including stratification, clustering, multiple stages of selection, and disproportionate sampling. These survey design complexities were taken into account for analysis in this study. The analysis was performed in SAS 9.2 and used chi-square tests and binary logistic regression. RESULTS: MEPS (2006) represented approximately 222 million non-institutionalised US adults. 42% (weighted) of this population reported a dental visit in the past 12 months. Dental visit numbers were observed to increase with age, with the 55-64-year-olds approximately 44% more likely than the 18-24-year olds to have visited the dentist in the past year. Hispanics were 48% less likely to report a dental visit compared to Non-Hispanic Whites. Respondents with public- or no- dental insurance were less likely to report a dental visit than persons with private dental coverage. CONCLUSIONS: Under half the US adult civilian non-institutionalised population reported a dental visit during 2006. To help address utilisation disparities, creative initiatives and systemic approaches aimed at groups currently utilising OHCS less often could be an important step towards oral health equity.

Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus.

BACKGROUND: We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells. METHODS: The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing. We investigated gene expression in vivo using reverse-transcription PCR and tissue microarrays, and studied the phenotypic consequences of forced gene overexpression. RESULTS: The rearrangement involved lipoprotein lipase (LPL) and peroxisome biogenesis factor-5 (PEX5). Whereas LPL-PEX5 was expressed at low levels and contained a premature stop codon, PEX5-LPL was highly expressed and encoded a full-length chimeric protein (including the majority of the LPL coding region). Consistent with these findings, PEX5 was constitutively expressed in normal cervical squamous cells, whereas LPL expression was negligible. The LPL gene was rearranged in 1 out of 151 cervical SCCs, whereas wild-type LPL overexpression was common, being detected in 10 out of 28 tissue samples and 4 out of 10 cell lines. Forced overexpression of wild-type LPL and PEX5-LPL fusion transcripts resulted in increased invasiveness in cervical SCC cells, attributable to the C-terminal non-catalytic domain of LPL, which was retained in the fusion transcripts. CONCLUSION: This is the first demonstration of an expressed fusion gene in cervical SCC. Overexpressed wild-type or translocated LPL is a candidate for targeted therapy.

ApoA-I mimetics favorably impact cyclooxygenase 2 and bioactive lipids that may contribute to cardiometabolic syndrome in chronic treated HIV.

OBJECTIVE: We investigated whether apolipoprotein A-I (apoA-I) mimetic peptides 4F and 6F can be a novel therapeutic strategy to reduce blood and gut bioactive lipids, proinflammatory effects of endotoxin (LPS) and aberrant activation of cyclooxygenase 2 (COX-2) as instigators of increased risk for cardiometabolic disease in chronic treated HIV. METHODS: We used two humanized murine models of chronic treated HIV infection (n = 109 mice) and gut explants from HIV infected (n = 10) persons to determine whether Tg6F and 4F attenuate in vivo and ex vivo increased blood and gut bioactive lipids (measured by mass spectrometry) and intestinal protein levels of COX-2 (measured by immunoassays) in chronic treated HIV. RESULTS: In these models of HIV, when compared to HIV-1 infected mice on antiretroviral therapy (ART) alone, oral Tg6F in combination with ART attenuated increases in plasma and gut bioactive lipids (and particularly COX lipids) and intestinal COX-2. 4F and Tg6F also reduced ex vivo production of COX-2 protein and associated secretion of bioactive lipids in gut explants from HIV-1 infected persons treated with LPS. CONCLUSION: ApoA-I mimetics favorably impact the proinflammatory effects of LPS, COX-2 and production of bioactive lipids that collectively drive gut and systemic inflammation in chronic treated HIV. Given prior experimental evidence that the proinflammatory effects of LPS, COX-2 and gut dysfunction contribute to cardiometabolic syndrome in chronic HIV, apoA-I mimetic peptides may be a novel therapy to treat cardiometabolic syndrome in chronic HIV.

The quality of life index: a pilot study integrating treatment efficacy and quality of life in oncology.

The majority of women diagnosed with breast cancer will experience some form of drug-related toxicity and subsequent impairments in Health-related Quality of Life (HRQoL). Despite this, HRQoL is assessed inconsistently and there is no validated method to integrate HRQoL data into the assessment of therapeutic agents. This proof of concept study utilizes data from the neoadjuvant I-SPY 2 clinical trial to describe the development of the Quality of Life Index (QoLI) measure. The QoLI represents a single composite score that incorporates validated longitudinal measures of clinical efficacy and QoL and one that permits a more comprehensive, direct comparison of individual therapeutic agents. Preliminary data suggest the QoLI is able to distinguish between agents based on their efficacy and toxicity; with further validation, the QoLI has the potential to provide more patient-centered evaluations in clinical trials and help guide treatment decision making in breast cancer and other oncologic diseases.

Lead contamination around secondary smelters: estimation of dispersal and accumulation by humans.

A high rate of lead fallout around two secondary lead smelters originated mainly from episodal large-particulate emissions from low-level fugitive sources rather than from stack fumes. The lead content of dustfall, and consequently of soil, vegetation, and outdoor dust, decreased exponentially with distance from the two smelters. Between 13 and 30 percent of the children living in the contaminated areas had absorbed excessive amounts of lead (more than 40 micrograms per 100 milliliters of blood and more than 100 micrograms per gram of hair) as compared with less than 1 percent in a control group. A relationship between blood and hair was established which indicated that the absorption was fairly constant for most children examined. It seemned that the ingestion of contaminated dirt and dusts rather than "paint pica" was the major route of lead intake. Metabolic changes were found in most of 21 children selected from those with excessive lead absorption; 10 to 15 percent of this group showed subtle neurological dysfunctions and minor psychomotor abnormalities.

Professional charges not reimbursed to dentists in the U.S.: evidence from Medical Expenditure Panel Survey, 1996.

OBJECTIVES: This cross-sectional study examined professional charges not paid to dentists. METHODS: This analysis used logistic regression in SUDAAN examining the 1996 MEPS data from 12,931 adults. RESULTS: Among people incurring dental care charges, 13.6% had more than $50 of unpaid charge (UC). The percapita UC was $53.30. Total UC was higher for highest income group [45.4% of total] compared to lowest income group [26.0%]. The percapita UC of $76.70 for low income group was significantly greater than for high income group ($47.80, P < 0.01). More Medicaid recipients (52% vs. non-recipients: 12%) incurred at least $50 in UC (P < 0.01). Adjusted odds of incurring UC were greater for those employed (OR = 1.3, 95% CI: 1.0-1.7), and for those with private insurance (OR: 1.5, CI: 1.3-1.9). Number of dental procedure types modified the association between Medicaid recipient and UC (OR = 13.6 for Medicaid recipients undergoing multiple procedure types; OR: 2.3 for Medicaid non-recipients with multiple procedure types; OR: 1.9 for Medicaid recipients receiving single dental procedure. CONCLUSIONS: Having private insurance, being unemployed and being Medicaid insured undergoing multiple procedure were strongest predictors of UC.

Albendazole therapy for single small enhancing CT lesions (SSECTL) in the brain in epilepsy.

BACKGROUND: Single small enhancing CT lesions (SSECTL) of the brain with or without perifocal oedema are common in patients with symptomatic epilepsy in India. Solitary cysticercus granuloma, a benign form of parenchymal neurocysticercosis, is considered to be the most common aetiology for SSECTL. Definite information is lacking regarding the effectiveness of antiparasitic treatment on resolution of these lesions and on long term seizure recurrence. OBJECTIVE: To evaluate the response to albendazole treatment in patients who had SSECTL and new onset seizures treated with antiepileptic drugs (AED) in a prospective clinical trial. METHODS: 43 patients who presented with new onset seizures and were documented to have SSECTL were alternatively allocated to receive albendazole 15 mg/kg/day for 2 weeks or no cysticidal therapy. All patients were treated with AED and followed for at least 6 months for seizure recurrence, and serial CT scans were obtained at 4 weeks, 3 months and at study completion. RESULTS: 28 (65%) patients were aged 5-25 years and 31 (72%) presented clinically with partial motor seizures with or without generalisation. Most of the SSECTL were ring lesions (75%) and located in and around the sensory-motor cortex at the gray-white junction (65%). In the albendazole group, 56% of patients compared with 35% in the control group showed resolution of SSECTL (p = 0.154) at 1 month. 22 of 23 patients (95.6%), who received albendazole, compared with 14 of 20 patients (70%) in the control group, demonstrated radiological resolution on study completion (p = 0.03). Punctate residual calcification and seizure recurrence were observed in four patients (9.3%) in the control group and in three (7%) patients in the albendazole group (p = 0.47). CONCLUSIONS: In patients presenting with seizures due to single viable parenchymal neurocysticercosis, albendazole hastens the resolution of SSECTL if treatment is given in the early phase of the illness.

Erythropoietin-induced deep vein thrombosis in myelodysplastic syndrome.

We report a rare case of deep vein thrombosis (DVT) secondary to erythropoietin (EPO) in an 89-year-old patient with myelodysplastic syndrome (MDS). The incidence of EPO-induced thrombotic episode increases with an absolute increase of hemoglobin (Hb) beyond >12 gm/dL or rate of increase of Hb level >1 gm/dL every 2 weeks.

Blood Bank on Wheels : A Novel Concept.

The concept of supplying safe and screened blood to casualties in war has been a problem over the years. Using the equipments available in a Corp Blood Supply Unit, we describe a simple modification of a vehicle for blood supply and its potential use as a mobile blood bank.

Synthesis and characterization of monodispersed water dispersible Fe3O4 nanoparticles and in vitro studies on human breast carcinoma cell line under hyperthermia condition.

Monodispersed Fe3O4 magnetic nanoparticles (MNPs) having size of 7 nm have been prepared from iron oleate and made water dispersible by functionalization for biomedical applications. Three different reactions employing thioglycolic acid, aspartic acid and aminophosphonate were performed on oleic acid coated Fe3O4. In order to achieve a control on particle size, the pristine nanoparticles were heated in presence of ferric oleate which led to increase in size from 7 to 11 nm. Reaction parameters such as rate of heating, reaction temperature and duration of heating have been studied. Shape of particles was found to change from spherical to cuboid. The cuboid shape in turn enhances magneto-crystalline anisotropy (Ku). Heating efficacy of these nanoparticles for hyperthermia was also evaluated for different shapes and sizes. We demonstrate heat generation from these MNPs for hyperthermia application under alternating current (AC) magnetic field and optimized heating efficiency by controlling morphology of particles. We have also studied intra-cellular uptake and localization of nanoparticles and cytotoxicity under AC magnetic field in human breast carcinoma cell line.

A peptide aptamer to antagonize BCL-6 function.

BCL-6 is a transcription factor essential for germinal centre B-cell development. The BCL-6 gene is involved in diffuse large-cell lymphoma and overexpressed in other types of non-Hodgkin's lymphoma and in high-grade breast cancer. BCL-6 is a transcriptional repressor whose N-terminal POZ domain mediates protein-protein interactions to exert its effects. Reasoning that disruption of POZ domain-mediated interactions may be an effective route to antagonizing the effects of BCL-6 in lymphoma, we screened a library for peptide aptamers that specifically bind to BCL-6 POZ and not the POZ domains of related proteins and describe here the first of these reagents, Apt48. Apt48 binds BCL-6 POZ in a manner distinct from the transcriptional corepressor SMRT, yet was found to prevent BCL-6-mediated repression of a luciferase reporter gene. Apt48 also reproduced several previously validated effects of BCL-6 inhibition. Notably, expression of the differentiation markers CD69, Blimp-1 and cyclin D2 was increased in B-cell lines when Apt48 was expressed. We also show that expression of Apt48 restores cytokine-mediated growth arrest to BCL-6 overexpressing cells. Thus, we have identified a peptide aptamer that affects a function of BCL-6 that is required to prevent differentiation of proliferating B cells.

Physiological requirement for both SH2 domains for phospholipase C-gamma1 function and interaction with platelet-derived growth factor receptors.

Two approaches have been utilized to investigate the role of individual SH2 domains in growth factor activation of phospholipase C-gamma1 (PLC-gamma1). Surface plasmon resonance analysis indicates that the individual N-SH2 and C-SH2 domains are able to specifically recognize a phosphotyrosine-containing peptide corresponding to Tyr 1021 of the platelet-derived growth factor (PDGF) beta receptor. To assess SH2 function in the context of the full-length PLC-gamma1 molecule as well as within the intact cell, PLC-gamma1 SH2 domain mutants, disabled by site-directed mutagenesis of the N-SH2 and/or C-SH2 domain(s), were expressed in Plcg1(-/-) fibroblasts. Under equilibrium incubation conditions (4 degrees C, 40 min), the N-SH2 domain, but not the C-SH2 domain, was sufficient to mediate significant PLC-gamma1 association with the activated PDGF receptor and PLC-gamma1 tyrosine phosphorylation. When both SH2 domains in PLC-gamma1 were disabled, the double mutant did not associate with activated PDGF receptors and was not tyrosine phosphorylated. However, no single SH2 mutant was able to mediate growth factor activation of Ca2+ mobilization or inositol 1,4,5-trisphosphate (IP3) formation. Subsequent kinetic experiments demonstrated that each single SH2 domain mutant was significantly impaired in its capacity to mediate rapid association with activated PDGF receptors and become tyrosine phosphorylated. Hence, when assayed under physiological conditions necessary to achieve a rapid biological response (Ca2+ mobilization and IP3 formation), both SH2 domains of PLC-gamma1 are essential to growth factor responsiveness.

Neuropathy associated with gluten sensitivity.

OBJECTIVES: To prospectively study the clinical, neurophysiological and neuropathological characteristics of axonal neuropathies associated with positive antigliadin antibodies and the prevalence of such neuropathies in a cohort of patients with sporadic axonal neuropathy. METHODS: Prospective screening (using antigliadin, antiendomysium and tissue transglutaminase antibodies) of patients with peripheral neuropathy attending a neurology clinic. RESULTS: 215 patients with axonal neuropathy were screened. 141 patients had symmetrical sensorimotor neuropathy, 47 had mononeuropathy multiplex, 17 had motor neuropathy and 10 had small-fibre neuropathy. Despite extensive investigations of the 215 patients, 140 had idiopathic neuropathy. Positive immunoglobulin (Ig)G with or without IgA antigliadin antibodies was found in 34% (47/140) of the patients with idiopathic neuropathy. This compares with 12% prevalence of these antibodies in the healthy controls. The prevalence of coeliac disease as shown by biopsy in the idiopathic group was at least 9% as compared with 1% in the controls. The clinical features of 100 patients (47 from the prevalence study and 53 referred from elsewhere) with gluten neuropathy included a mean age at onset of 55 (range 24-77) years and a mean duration of neuropathy of 9 (range 1-33) years. Gluten-sensitive enteropathy was present in 29% of patients. The human leucocyte antigen types associated with coeliac disease were found in 80% of patients. CONCLUSIONS: Gluten sensitivity may be aetiologically linked to a substantial number of idiopathic axonal neuropathies.

(A3) HIV Phenotypes, oral lesions, and management of HIV-related disease.

Workshop participants discussed: the role of HIV subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, CD4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. Regarding HIV, the literature revealed that Type I (HIV-I), in particular group M, is involved in the majority (90%) of documented infections, and groups N and O to a lesser extent. Viral envelope diversity led to the subclassification of the virus into nine subtypes, or clades-A-D, F-H, J, and K-each dominating in different geographical areas. HIV-2, currently occurring mostly in West Africa, appears to be less virulent. No evidence could be produced of any direct impact of type, subtype, or clade on oral lesions, and participants believed that further research is not feasible. Oral candidiasis in patients from resource-poor countries should be prevented. When the condition does occur, it should be treated until all clinical symptoms disappear. Oral rinsing with an antimicrobial agent was suggested to prevent recurrence of the condition, to reduce cost, and to prevent the development of antifungal resistance. Lawsone methyl ether, isolated from a plant (Rhinacanthus nasutus leaves) in Thailand, is a cost-effective mouthrinse with potent antifungal activity. Evidence from a carefully designed prospective longitudinal study on a Mexican cohort of HIV/AIDS patients, not receiving anti-retroviral treatment, revealed that the onset of oral candidiasis and oral hairy leukoplakia was heralded by a sustained reduction of CD4+, with an associated sharp increase in viral load. Analysis of the data obtained from a large cohort of HIV/AIDS patients in India could not establish a systemic or local cause of oral melanin pigmentation. A possible explanation was a dysfunctional immune system that increased melanin production. However, longitudinal studies may contribute to a better understanding of this phenomenon. Finally, a development plan was presented that could provide a reliable prediction of disease progression. To be useful in developing countries, the index should be independent of costly blood counts and viral load.

Aicardi syndrome: a report of five Indian cases.

Five Indian cases of Aicardi syndrome, aged 1-13 years and all with the classic triad of infantile spasm, corpus callosal agenesis and chorioretinal lacunae, were presented. The purpose of this report was to demonstrate the clinical, electroencephalographic (EEG) and radiological spectrum and the treatment outcome of this disorder among the Indians. None of the patient had any family history of similar illness. All had profound psychomotor impairment with no meaningful speech development. There were microphthalmia in 2, optic disc coloboma in 1, interhemispheric cyst in 1, periventricular heterotopia in 2 and thoracolumbar kyphoscoliosis in 2 cases. They all had early onset epilepsy and there were multiple types of seizures. Two cases (40%) had the characteristic dissociated burst-suppression pattern in EEG. Two cases whose antiepileptic medications included vigabatrin had complete control of seizure.