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Kalatu R Davies,1 Scott B Cantor,1 Abenaa M Brewster21Department of Health Services Research, 2Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: The incidence of contralateral prophylactic mastectomy (CPM) has increased among women with breast cancer, despite uncertain survival benefit and a declining incidence of contralateral breast cancer (CBC). Patient-related reasons for undergoing CPM include an overestimation of the risk of CBC, increased cancer worry, and a desire to improve survival. We summarize the existing literature on CBC risk and outcomes and the clinical benefit of CPM among women with unilateral breast cancer who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast. Published studies were retrieved from the MEDLINE database with the keywords “contralateral breast cancer” and “contralateral prophylactic mastectomy”. These include observational studies, clinical trials, survival analyses, and decision models examining the risk of CBC, the clinical and psychosocial effects of CPM, and other treatment strategies to reduce CBC risk. Studies that have evaluated CBC risk estimate it to be approximately 0.5% annually on average. Patient-related factors associated with an increased risk of CBC include carriers of BRCA1/2 mutations, young age at breast cancer, and strong family history of breast cancer in the absence of a BRCA1/2 mutation. Although CPM reduces the risk of CBC by approximately 94%, it may not provide a significant gain in overall survival and there is conflicting evidence that it improves disease-free survival among women with breast cancer regardless of estrogen receptor (ER) status. Therefore, alternative strategies such as the use of tamoxifen or aromatase inhibitors, which reduce the risk of CBC by approximately 50%, should be encouraged for eligible women with ER-positive breast cancers. Future research is needed to evaluate the impact of decision and educational tools that can be used for personalized counseling of patients regarding their CBC risk, the uncertain role of CPM, and alternative CBC risk reduction strategies.Keywords: contralateral prophylactic mastectomy, contralateral breast cancer, endocrine therapy, sporadic breast cancer, risk assessment

The heterostructure WO 3 /BiVO 4 -based photoanodes have garnered significant interest for photoelectrochemical (PEC) solar-driven water splitting to produce hydrogen. However, challenges such as inadequate charge separation and photocorrosion significantly hinder their performance, limiting overall solar-to-hydrogen conversion efficiency. The incorporation of cocatalysts has shown promise in improving charge separation at the photoanode, yet mitigating photocorrosion remains a formidable challenge. Amorphous metal oxide-based passivation layers offer a potential solution to safeguard semiconductor catalysts. We examine the structural, surface morphological, and optical properties of two-step-integrated sputter and spray-coated TiO 2 thin films and their integration onto WO 3 /BiVO 4 , both with and without NiOOH cocatalyst deposition. The J - V experiments reveal that the NiOOH cocatalyst enhances the photocurrent density of the WO 3 /BiVO 4 photoanode in water splitting reactions from 2.81 to 3.87 mA/cm 2 . However, during prolonged operation, the photocurrent density degrades by 52%. In contrast, integrated sputter and spray-coated TiO 2 passivation layer-coated WO 3 /BiVO 4 /NiOOH samples demonstrate a ∼88% enhancement in photocurrent density (5.3 mA/cm 2 ) with minimal degradation, emphasizing the importance of a strategic coating protocol to sustain photocurrent generation. We further explore the feasibility of using natural mine wastewater as an electrolyte feedstock in PEC generation. Two-compartment PEC cells, utilizing both fresh water and metal mine wastewater feedstocks exhibit 66.6 and 74.2 μmol/h cm 2 hydrogen generation, respectively. Intriguingly, the recovery of zinc (Zn 2+ ) heavy metals on the cathode surface in the mine wastewater electrolyte is confirmed through surface morphology and elemental analysis. This work underscores the significance of passivation layer and cocatalyst coating methodologies in a sequential order to enhance charge separation and protect the photoanode from photocorrosion, contributing to sustainable hydrogen generation. Additionally, it suggests the potential of utilizing wastewater in electrolyzers as an alternative to freshwater resources., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Understanding the processes that drive interpopulation differences in demography and population dynamics is central to metapopulation ecology. In colonial species, populations are limited by local resource availability. However, individuals from larger colonies will travel greater distances to overcome density-dependent competition. Consequently, these individuals may also experience greater carry-over effects and interpopulation differences in demography. To test this prediction, we use mark-recapture data collected over four decades from two breeding colonies of a seabird, the Manx shearwater ( Puffinus puffinus ), that exhibit strong spatial overlap throughout the annual cycle but differ in population size and maximum foraging distances. We quantify interpopulation differences and synchrony in rates of survival and assess whether local mean wind speeds act to strengthen or disrupt synchrony. In addition, we examine whether the imputed interpopulation differences in survival can generate population-level consequences. The colony where individuals travel further during the breeding season had slightly lower and more variable rates of survival, indicative of individuals experiencing greater carry-over effects. Fluctuations in survival were highly synchronous between the colonies, but neither synchronous, nor asynchronous, variation could be strongly attributed to fluctuations in local mean wind speeds. Finally, we demonstrate that the imputed interpopulation differences in rates of survival could lead to considerable differences in population growth. We hypothesise that the observed interpopulation differences in rates of adult survival reflect carry-over effects associated with foraging distances during the breeding season. More broadly, our results highlight that breeding season processes can be important for understanding interpopulation differences in the demographic rates and population dynamics of long-lived species, such as seabirds., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

For the first time, we demonstrate a photoelectrocatalysis technique for simultaneous surfactant pollutant degradation and green hydrogen generation using mesoporous WO 3 /BiVO 4 photoanode under simulated sunlight irradiation. The materials properties such as morphology, crystallite structure, chemical environment, optical absorbance, and bandgap energy of the WO 3 /BiVO 4 films are examined and discussed. We have tested the anionic type (sodium 2-naphthalenesulfonate (S2NS)) and cationic type surfactants (benzyl alkyl dimethylammonium compounds (BAC-C12)) as model pollutants. A complete removal of S2NS and BAC-C12 surfactants at 60 and 90 min, respectively, by applying 1.75 V applied potential vs RHE to the circuit, under 1 sun was achieved. An interesting competitive phenomenon for photohole utilization was observed between surfactants and adsorbed water. This led to the formation of H 2 O 2 from water alongside surfactant degradation (anode) and hydrogen evolution (cathode). No byproducts were observed after the direct photohole mediated degradation of surfactants, implying its advantage over other AOPs and biological processes. In the cathode compartment, 82.51 μmol/cm 2 and 71.81 μmol/cm 2 of hydrogen gas were generated during the BAC-C12 and S2NS surfactant degradation process, respectively, at 1.75 V RHE applied potential., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Most of our understanding of the ecology and evolution of avian influenza A virus (AIV) in wild birds is derived from studies conducted in the northern hemisphere on waterfowl, with a substantial bias towards dabbling ducks. However, relevant environmental conditions and patterns of avian migration and reproduction are substantially different in the southern hemisphere. Through the sequencing and analysis of 333 unique AIV genomes collected from wild birds collected over 15 years we show that Australia is a global sink for AIV diversity and not integrally linked with the Eurasian gene pool. Rather, AIV are infrequently introduced to Australia, followed by decades of isolated circulation and eventual extinction. The number of co-circulating viral lineages varies per subtype. AIV haemagglutinin (HA) subtypes that are rarely identified at duck-centric study sites (H8-12) had more detected introductions and contemporary co-circulating lineages in Australia. Combined with a lack of duck migration beyond the Australian-Papuan region, these findings suggest introductions by long-distance migratory shorebirds. In addition, on the available data we found no evidence of directional or consistent patterns in virus movement across the Australian continent. This feature corresponds to patterns of bird movement, whereby waterfowl have nomadic and erratic rainfall-dependant distributions rather than consistent intra-continental migratory routes. Finally, we detected high levels of virus gene segment reassortment, with a high diversity of AIV genome constellations across years and locations. These data, in addition to those from other studies in Africa and South America, clearly show that patterns of AIV dynamics in the Southern Hemisphere are distinct from those in the temperate north., Competing Interests: The authors have declared that no competing interests exist.

The embryonated chicken egg (ECE) is routinely used for the laboratory isolation and adaptation of Bluetongue virus (BTV) in vitro. However, its utility as an alternate animal model has not been fully explored. In this paper, we evaluated the pathogenesis of BTV in ovo using a pathogenic isolate of South African BTV serotype 3 (BTV-3) derived from the blood of an infected sheep. Endothelio- and neurotropism of BTV-3 were observed by immunohistochemistry of non-structural protein 1 (NS1), NS3, NS3/3a, and viral protein 7 (VP7) antigens. In comparing the pathogenicity of BTV from infectious sheep blood with cell-culture-passaged BTV, including virus propagated through a Culicoides -derived cell line (KC) or ECE, we found virus attenuation in ECE following cell-culture passage. Genomic analysis of the consensus sequences of segments (Seg)-2, -5, -6, -7, -8, -9, and -10 identified several nucleotide and amino-acid mutations among the cell-culture-propagated BTV-3. Deep sequencing analysis revealed changes in BTV-3 genetic diversity in various genome segments, notably a reduction of Seg-7 diversity following passage in cell culture. Using this novel approach to investigate BTV pathogenicity in ovo , our findings support the notion that pathogenic BTV becomes attenuated in cell culture and that this change is associated with virus quasispecies evolution.

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise. IMPORTANCE We describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016., (Copyright © 2018 American Society for Microbiology.)

We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility to oseltamivir and zanamivir. The NAs of four viruses were identified as extreme outliers to oseltamivir, based on statistical analysis by box plots, with IC 50 values ranging from 46 to 62 nM. The NAs of two of these viruses from Sumatra and Aceh, had an N294S substitution, while one virus from Sulawesi had an S246N NA substitution. The NAs of all four viruses showed a specific loss of slow binding to oseltamivir in an IC 50 kinetics assay. As observed in our previous surveillance, there was only a minimal effect on the sensitivity to zanamivir or peramivir for these mutants or any of the other isolates tested. The continued circulation of subtype H5N1 viruses in avian species poses an on-going zoonotic threat. The fact that we continue to identify avian isolates with naturally occurring mutations conferring reduced oseltamivir susceptibility remains a concern, given oseltamivir will be a key antiviral in the event of a new pandemic emerging., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Family history of breast cancer is associated with an increased risk of contralateral breast cancer (CBC) even in the absence of mutations in the breast cancer susceptibility genes BRCA1/2. We compared quality-adjusted survival after contralateral prophylactic mastectomy (CPM) with surveillance only (no CPM) among women with breast cancer incorporating the degree of family history., Methods: We created a microsimulation model for women with first-degree, second-degree, and no family history treated for a stage I, II, or III estrogen receptor (ER)-positive or ER-negative breast cancer at the ages of 40, 50, 60, and 70. The model incorporated a 10-year posttreatment period for risk of developing CBC and/or dying of the primary cancer or CBC. For each patient profile, we used 100,000 microsimulation trials to estimate quality-adjusted life expectancy for the clinical strategies CPM and no CPM., Results: CPM showed minimal improvement on quality-adjusted life expectancy among women age 50-60 with no or a unilateral first-degree or second-degree family history (decreasing from 0.31 to -0.06 quality-adjusted life-years (QALYs)) and was unfavorable for most subgroups of women age 70 with stage III breast cancer regardless of degree of family history (range -0.08 to -0.02 QALYs). Sensitivity analysis showed that the highest predicted benefit of CPM assuming 95 % risk reduction in CBC was 0.57 QALYs for a 40-year-old woman with stage I breast cancer who had a first-degree relative with bilateral breast cancer., Conclusions: Women age 40 with stage I breast cancer and a first-degree relative with bilateral breast cancer have a QALY benefit from CPM similar to that reported for BRCA1/2 mutation carriers. For most subgroups of women, CPM has a minimal to no effect on quality-adjusted life expectancy, irrespective of family history of breast cancer.

Background: See-and-treat using loop electrosurgical excision procedure (LEEP) has been recommended as an alternative in managing high-grade cervical squamous intraepithelial lesions, but existing literature lacks evidence of the strategy's cost-effectiveness. We evaluated the overtreatment and cost-effectiveness of the see-and-treat strategy compared with usual care., Methods: We modeled a hypothetical cohort of 40-year-old females who had not been screened for cervical cancer and followed them through their lifetimes using a Markov model. From a U.S. health-system perspective, the analysis was conducted in 2012 dollars and measured effectiveness in quality-adjusted life-years (QALY). We estimated incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $50,000/QALY. The robustness of the see-and-treat strategy's cost-effectiveness and its overtreatment rates were further examined in various sensitivity analyses., Results: In the base-case, the see-and-treat strategy yielded an ICER of $70,774/QALY compared with usual care. For most scenarios in the deterministic sensitivity analysis, this strategy had ICERs larger than $50,000/QALY, and its cost-effectiveness was sensitive to the disutility of LEEP treatment and biopsy-directed treatment adherence under usual care. Probabilistic sensitivity analysis showed that the see-and-treat strategy had a 50.1% chance to be cost-effective. It had an average overtreatment rate of 7.1% and a 78.8% chance to have its overtreatment rate lower than the 10% threshold., Conclusion: The see-and-treat strategy induced an acceptable overtreatment rate. Its cost-effectiveness, compared with usual care, was indiscriminating at the chosen willingness-to-pay threshold but much improved when the threshold increased., Impact: The see-and-treat strategy was reasonable for particular settings, that is, those with low treatment adherence. Cancer Epidemiol Biomarkers Prev; 25(5); 807-14. ©2016 AACR., (©2016 American Association for Cancer Research.)

Purpose: We compared overall survival and influencing factors between Asian-American women as a whole and by subgroup with white women with cervical cancer., Methods: Cervical cancer data were from the Surveillance, Epidemiology, and End Results registry; socioeconomic information was from the Area Health Resource File. We used standard tests to compare characteristics between groups; the Kaplan-Meier method with log-rank test to assess overall survival and compare it between groups; and Cox proportional hazards models to determine the effect of race and other covariates on overall survival (with and/or without age stratification)., Results: Being 3.3 years older than white women at diagnosis (P < .001), Asian-American women were more likely to be in a spousal relationship, had more progressive disease, and were better off socioeconomically. Women of Filipino, Japanese, and Korean origin had similar clinical characteristics compared to white women. Asian-American women had higher 36- and 60-month survival rates (P = .004 and P = .013, respectively), higher overall survival rates (P = .049), and longer overall survival durations after adjusting for age and other covariates (hazard ratio = 0.77, 95% confidence interval: 0.68-0.86). Overall survival differed across age strata between the two racial groups. With the exception of women of Japanese or Korean origin, Asian-American women grouped by geographic origin had better overall survival than white women., Conclusions: Although Asian-American women, except those of Japanese or Korean origin, had better overall survival than white women, their older age at cervical cancer diagnosis suggests that they have less access to screening programs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening., Methods: A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses., Results: In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear., Conclusion: Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.

Introduction: Since colposcopy helps to detect cervical cancer in its precancerous stages, as new strategies and technologies are developed for the clinical management of cervical neoplasia, precisely determining the accuracy of colposcopy is important for characterizing its continued role. Our objective was to employ a more precise methodology to estimate of the accuracy of colposcopy to better reflect clinical practice., Study Design: For each patient, we compared the worst histology result among colposcopically positive sites to the worst histology result among all sites biopsied, thereby more accurately determining the number of patients that would have been underdiagnosed by colposcopy than previously estimated., Materials and Methods: We utilized data from a clinical trial in which 850 diagnostic patients had been enrolled. Seven hundred and ninety-eight of the 850 patients had been examined by colposcopy, and biopsy samples were taken at colposcopically normal and abnormal sites. Our endpoints of interest were the percentages of patients underdiagnosed, and sensitivity and specificity of colposcopy., Results: With the threshold of low-grade squamous intraepithelial lesions for positive colposcopy and histology diagnoses, the sensitivity of colposcopy decreased from our previous assessment of 87.0% to 74.0%, while specificity remained the same. The drop in sensitivity was the result of histologically positive sites that were diagnosed as negative by colposcopy. Thus, 28.4% of the 798 patients in this diagnostic group would have had their condition underdiagnosed by colposcopy in the clinic., Conclusions: In utilizing biopsies at multiple sites of the cervix, we present a more precise methodology for determining the accuracy of colposcopy. The true accuracy of colposcopy is lower than previously estimated. Nevertheless, our results reinforce previous conclusions that colposcopy has an important role in the diagnosis of cervical precancer.

In March 2014, avian influenza in poultry in Laos was caused by an emergent influenza A(H5N6) virus. Genetic analysis indicated that the virus had originated from reassortment of influenza A(H5N1) clade 2.3.2.1b, variant clade 2.3.4, and influenza A(H6N6) viruses that circulate broadly in duck populations in southern and eastern China.

Midfoot break (MFB) is a foot deformity that can occur when ankle dorsiflexion is restricted due to muscle spasticity or contractures, causing abnormal increased motion through the midfoot. MFB has been previously described in terms of forefoot (FF) and hindfoot (HF) motion in the sagittal plane. The purpose of this study was to further classify MFB by describing FF and HF motion in the coronal and transverse planes along with plantar pressures, with the goal of optimizing treatment of this deformity. Three-dimensional foot kinematics were assessed using a multi-segment foot model in children with MFB (n=30) and children with no foot or gait abnormalities (n=30). The MFB group was subdivided into three categories: (1) Pronated MFB, (2) Supinated MFB and (3) Flat Foot MFB. Unique patterns of plantar pressures and foot kinematics were identified for each MFB group. The Pronated MFB group had increased medial midfoot pressures, increased forefoot pronation, and increased external forefoot rotation (forefoot abductus). The Supinated MFB group had increased lateral midfoot pressures, increased forefoot supination, and increased internal forefoot rotation (forefoot adductus). In the Flat Foot MFB group, midfoot pressures were increased and distributed uniformly between the medial and lateral sides, forefoot pronation was increased, and internal forefoot rotation was present. By combining this new information with previously reported methods of measuring sagittal plane kinematics of MFB, it is now possible to characterize midfoot break in terms of severity and foot-floor contact pattern., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: To assess "alternate forms" reliability and inter-rater reliability of Gross Motor Function Classification System (GMFCS) scores., Methods: Fifty randomly selected children with cerebral palsy were divided into two groups: (1) GMFCS score assigned during gait assessment ("GMFCS previously assigned") and (2) no GMFCS score assigned. Using database information, two physiotherapists independently determined GMFCS scores for 25 children from the "previously assigned" group, and 25 from the "no score assigned" group. Therapists compared their recently assigned scores for the "previously assigned" group, discussing discrepancies until attaining agreement. This group's consensus scores were compared to GMFCS scores assigned at time of actual assessment to calculate "alternate forms" reliability., Results: Between-therapist agreements were kappa = 0.84 for "GMFCS previously assigned" group and 0.95 for "no GMFCS assigned" group. Kappa agreement between direct assessment and retrospectively assigned scores for the "GMFCS previously assigned" group was 0.79., Conclusions: Retrospective GMFCS scores can be reliably assigned.

Midfoot break (MFB) is a foot deformity that occurs most commonly in children with cerebral palsy (CP), but may also affect children with other developmental disorders. Dynamic MFB develops because the muscles that cross the ankle joint are hypertonic, resulting in a breakdown and dysfunction of the bones within the foot. In turn, this creates excessive motion at the midfoot. With the resulting inefficient lever arm, the foot is then unable to push off the ground effectively, resulting in an inadequate and painful gait pattern. Currently, there is no standard quantitative method for detecting early stages of MFB, which would allow early intervention before further breakdown occurs. The first step in developing an objective tool for early MFB diagnosis is to examine the difference in dynamic function between a foot with MFB and a typical foot. Therefore, the main purpose of this study was to compare the differences in foot motion between children with MFB and children with typical feet (Controls) using a multi-segment kinematic foot model. We found that children with MFB had a significant decrease in peak ankle dorsiflexion compared to Controls (1.3 ± 6.4° versus 8.6 ± 3.4°) and a significant increase in peak midfoot dorsiflexion compared to Controls (15.2 ± 4.9° versus 6.4 ± 1.9°). This study may help clinicians track the progression of MFB and help standardize treatment recommendations for children with this type of foot deformity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Medical decision makers would like to use decision theory to determine optimal treatment strategies for patients, but this requires priors, likelihoods, and losses. It can be very difficult to specify a loss or utility function in a medical setting, especially when considering both patient health outcomes and economic costs. These issues led to the development of Inverse Decision Theory (IDT), which involves determining the set of losses under which a given decision rule is optimal., Methods: We apply IDT to the current standard of care for the diagnosis and treatment of precancerous lesions to the cervix, using a Bayesian approach to estimate the probabilities associated with diagnostic tests and make inferences about the region of optimality. There are two ways in which Inverse Decision Theory can be useful: (i) if the decision rule of interest is optimal, then we obtain information about the losses for the optimal treatment strategy, and (ii) if the decision rule of interest is not optimal, then we characterize the losses under which it would be optimal, and assess whether or not it contains reasonable values of the losses., Results: This paper introduces important clinical results: in particular, we find that the current standard of care for cervical precancer is probably not optimal, and a new decision rule which requires a confirmatory biopsy for all patients with a positive Pap smear test result is better., Conclusion: We have developed a very general and flexible approach for evaluating treatment strategies that could prove useful in a variety of medical applications.

Background: Palmtop computers provide a promising mobile platform to address barriers to computer-based supports for people with intellectual disabilities. This study evaluated a specially designed interface to make navigation and features of palmtop computers more accessible to users with intellectual disabilities., Method: The specialised cognitively accessible interface was compared with a standard Windows CE interface. Participants completed a structured set of navigation/computer use tasks using both the experimental and control conditions. Measurements included the amount of assistance needed and errors made in completing the navigation/computer use tasks., Results: Participants (N = 32) made significantly fewer errors (p<.001) and required significantly fewer prompts (p<.001) while using the specialised software interface compared to the mainstream Windows interface., Conclusions: The research demonstrates the feasibility of using special software design methods, such as linear program flows, error minimisation and the incorporation of repetition and consistency, to improve access to palmtop computers for individuals with intellectual disabilities. Issues related to designing cognitively accessible interfaces are discussed.

When a permanent maxillary canine erupts apical to the permanent lateral incisor and the deciduous canine, resorption typically takes place only on the deciduous canine root. An understanding of this differential resorption could provide insight into the reasons for excessive iatrogenic root resorption during orthodontic tooth movement. The purpose of the present study was to examine the response of roots of permanent lateral incisors and deciduous canines to simulated resorption, and to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine. Groups of maxillary permanent lateral incisor and deciduous canine roots were exposed to 5 combinations of Ten Cate demineralizing solution, Ten Cate demineralizing solution with EDTA, and a Type I collagenase solution. Sections of the roots were examined under a polarized light microscope. Analysis of variation of the resulting root lesions demonstrated that the lesion depths for deciduous canines were greater than those for permanent lateral incisors when averaged across 4 of the conditions (F(1,24) = 7.49, P =.0115). On average, deciduous canine roots demonstrated lesions 10% deeper than did permanent lateral incisor roots. We concluded that when deciduous canine and permanent lateral incisor roots are subjected to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine, significantly deeper demineralized lesions are seen in the deciduous roots compared with the permanent roots. This finding may partially explain the differential root resorption during permanent tooth eruption.

In human and mouse, most imprinted genes are arranged in chromosomal clusters. Their linked organization suggests co-ordinated mechanisms controlling imprinting and gene expression. The identification of local and regional elements responsible for the epigenetic control of imprinted gene expression will be important in understanding the molecular basis of diseases associated with imprinting such as Beckwith-Wiedemann syndrome. We have established a complete contig of clones along the murine imprinting cluster on distal chromosome 7 syntenic with the human imprinting region at 11p15.5 associated with Beckwith-Wiedemann syndrome. The cluster comprises approximately 1 Mb of DNA, contains at least eight imprinted genes and is demarcated by the two maternally expressed genes Tssc3 (Ipl) and H19 which are directly flanked by the non-imprinted genes Nap1l4 (Nap2) and Rpl23l (L23mrp), respectively. We also localized Kcnq1 (Kvlqt1) and Cd81 (Tapa-1) between Cdkn1c (p57(Kip2)) and Mash2. The mouse Kcnq1 gene is maternally expressed in most fetal but biallelically transcribed in most neonatal tissues, suggesting relaxation of imprinting during development. Our findings indicate conserved control mechanisms between mouse and human, but also reveal some structural and functional differences. Our study opens the way for a systematic analysis of the cluster by genetic manipulation in the mouse which will lead to animal models of Beckwith-Wiedemann syndrome and childhood tumours.

Electrocardiographic (ECG) changes are reported frequently after subarachnoid haemorrhage (SAH). The aim of this study was to investigate the functional significance of ECG changes by echocardiographic assessment of cardiac function. Forty-five patients with intracranial aneurysms were studied. All patients had a 12-lead ECG and a two-dimensional echocardiogram. After patients with an history of chronic cardiac disease (n = 4) were excluded, only four patients were found to have wall motion abnormalities. These patients had only minor ECG abnormalities, but severe neurological dysfunction. Conversely, patients with other ECG abnormalities including the deep inverted T waves associated usually with SAH, had normal echocardiograms. We conclude that the ECG is not an accurate predictor of myocardial function after SAH and that myocardial dysfunction is related more closely to severity of neurological condition.

Continuous on-line breath-by-breath measurement of pulmonary gas exchange was used to monitor the increase in oxygen uptake (VO2) and carbon dioxide excretion (VCO2) induced by the oxidative phosphorylation uncoupling agent 2, 4-dinitrophenol (DNP) in 10 dogs. With incremental doses of DNP totaling 5 mg/kg, the continuously monitored VO2 increased within 2-3 min after the first injection of the drug. VCO2 showed a similar response 4-6 min after the first injection. Temperature increase due to the pharmacological oxidative phosphorylation uncoupling required 20-30 min for a discernible change at this dose. This study also demonstrated a modified and compromised response to the drug in dogs where oxygen delivery was limited by mechanical ventilation.

The authors investigated the spinal blood flow and metabolic effects of subarachnoid clonidine in conscious rats prepared with chronically implanted subarachnoid catheters. For the blood flow experiments, rats received saline (n = 7) or clonidine 20 nmol (7 micrograms; n = 6), 100 nmol (27 micrograms; n = 5), or 400 nmol (107 micrograms; n = 7) intrathecally. Another group of rats received clonidine 400 nmol intravenously (n = 4). Spinal glucose utilization was measured in rats that received either saline (n = 5) or clonidine 100 nmol (n = 5) intrathecally. Spinal cord blood flow (SCBF) and glucose utilization were measured in five gray and three white matter areas of lumbar spinal cord 15 min after drug administration with the autoradiographic iodo-[14C]-antipyrine and 2-[14C]-deoxyglucose methods, respectively. Physiologic differences between the groups were minor. Rats in the blood flow experiments that received clonidine 100 nmol had a slightly lower arterial PO2 level (70 +/- 1 vs. 82 +/- 3 mmHg; P less than 0.05), whereas those in the glucose utilization group were mildly hypocarbic (PCO2 27 +/- 1 vs. 32 +/- 2 mmHg; P less than 0.01) relative to control animals. Only animals that received 400 nmol clonidine intrathecally had significant analgesia, as assessed by the tail-flick test. One control animal for the metabolism experiments was technically unsatisfactory and was excluded from data analysis. Subarachnoid clonidine reduced both SCBF and glucose utilization. In spinal gray matter, the largest decreases in flow (32-44%; P less than 0.01) occurred with 20 nmol clonidine, whereas flow decreased least (12-27%) with the 400-nmol dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac output was measured by both indocyanine green dye dilution and the direct Fick method using computer-calculated values for oxygen consumption and carbon dioxide excretion in eight mechanically ventilated dogs anesthetized with pentobarbital, with either tubocurarine or succinylcholine intravenous drip for neuromuscular relaxation. Sequential measurements were made during the anesthesia and in response to pharmacologically induced increased cardiac output using doxapram hydrochloride (1.5 mg/kg) given intravenously. The purpose of this project was to investigate the accuracy and reliability of the direct Fick measurements during anesthesia using computer-calculated measurements of pulmonary gas exchange and, since, these measurements have not been reported in detail previously, to establish tentative control values for future projects. The correlation of dye and direct Fick measurements of cardiac output during the first hour after induction of anesthesia was very good (r = 0.85 for all dye-carbon dioxide Fick values; r = 0.83 for all dye-oxygen Fick values.

Expired gas flow volume (VE), carbon dioxide excretion (Vco2) and oxygen consumption (Vo2) were measured continuously for 2-minute periods at 15-minute intervals during at least 75 minutes of general anesthesia and surgery in clinical patients. Analog tape-recorded outputs from an infrared CO2 analyzer, from a rapid polarographic O2 analyzer, and from a pneumotachograph were subsequently processed by a general purpose digital computer. Values for VE, VCO2, and VO2 in a group of 50 normal paralyzed endotracheally intubated women with balanced N2O-O2-fentanyl anesthesia for lower abdominal surgery compare favorably with the few published reports of similar measurements. The measured response to anesthesia and surgery in most patients included a progressive increase in O2 uptake and a concurrent but not necessarily simultaneous decrease in CO2 output with a consequent decreased respiratory gas exchange ratio (RE).

For two years an office computer was used to identify patients to prompt for opportunistic screening and call for systematic screening. After the two years 92% of patients on the list had had blood pressure readings recorded within the previous five years, of which 34% resulted from special prompts and 22% from screening letters. Those who failed to respond to letters were sent questionnaires, and their records were compared with those of screened patients. With the help of a microcomputer it is practicable to sustain a continuous screening rate of between 90% and 95%.

We use our office computer to record and issue repeat prescriptions. Each month we look at a printout to see how many times a drug has been prescribed, with the goal of limiting our practice formulary. We have reduced by more than 10% the range of drugs that we use in the practice and have the possibility of knowing dose ranges, actions, interactions, and side effects of all the drugs used in the practice.