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The promise of quantum computing lies in harnessing programmable quantum devices for practical applications such as efficient simulation of quantum materials and condensed matter systems. One important task is the simulation of geometrically frustrated magnets in which topological phenomena can emerge from competition between quantum and thermal fluctuations. Here we report on experimental observations of equilibration in such simulations, measured on up to 1440 qubits with microsecond resolution. By initializing the system in a state with topological obstruction, we observe quantum annealing (QA) equilibration timescales in excess of one microsecond. Measurements indicate a dynamical advantage in the quantum simulation compared with spatially local update dynamics of path-integral Monte Carlo (PIMC). The advantage increases with both system size and inverse temperature, exceeding a million-fold speedup over an efficient CPU implementation. PIMC is a leading classical method for such simulations, and a scaling advantage of this type was recently shown to be impossible in certain restricted settings. This is therefore an important piece of experimental evidence that PIMC does not simulate QA dynamics even for sign-problem-free Hamiltonians, and that near-term quantum devices can be used to accelerate computational tasks of practical relevance.

Objectives: The aim of this study was to explore the barriers to accessing cancer services faced by adults with pre-existing physical disabilities., Design: Cross-sectional, exploratory qualitative study. Data were collected by semistructured interviews and analysed thematically., Setting: Participants were recruited through statutory and third sector organisations in England and Wales between October 2017 and October 2018., Participants: 18 people with a diagnosis of cancer and a pre-existing physical disability., Results: The findings illustrate that people with physical disabilities in England and Wales face a variety of barriers to accessing cancer services. The overall theme that emerged was that participants experienced a lack of attitudinal and institutional preparation both from healthcare professionals and healthcare facilities. This overall theme is illustrated through three subthemes: lack of acknowledgment of disability, unseeing disability and physical inaccessibility., Conclusions: As the population ages and increasing numbers of people live with cancer and disability, it is important to develop knowledge to respond to the needs of this population. The mere existence of services does not guarantee their usability. Services need to be relevant, flexible, and accessible and offered in a respectful manner. It is important that healthcare professionals work towards inclusive healthcare provision, enabling the utilisation of services by all. Necessary steps to be taken include better communication between the various professionals and across the different teams involved in patients' care, raising awareness of how physical disability can affect or interact with cancer-related treatment and creating more accessible physical environments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Health professionals, including social workers, community health workers, public health workers, and licensed health care providers, share common interests and responsibilities in promoting health equity and improving social determinants of health-the conditions in which people live, work, play, and learn. We summarize the underlying causes of health inequity and comparatively poor health outcomes in the United States. We describe barriers to realizing the hope embedded in the 2010 Patient Protection and Affordable Care Act, that moving away from fee-for-service payments will naturally drive care upstream as providers respond to greater financial risk by undertaking greater prevention efforts for the health of their patients. We assert that health equity should serve as the guiding framework for achieving the Triple Aim of health care reform and outline practical opportunities for improving care and promoting stronger efforts to address social determinants of health. These proposals include developing a dashboard of measures to assist providers committed to health equity and community-based prevention and to promote institutional accountability for addressing socioeconomic factors that influence health.

There is strong evidence that high yielding dairy cows are extremely susceptible to infectious diseases, and that this has severe economic consequences for the dairy industry and welfare implications. Here we present preliminary functional evidence showing that the innate immune response differs between cow breeds. The ability of macrophages (MØ) to kill pathogens depends in part on oxygen-dependent and independent mechanisms. The oxygen-dependent mechanisms rely on the generation of reactive oxygen and nitrogen species (ROS/RNS, respectively). ROS production has been shown to activate the inflammasome complex in MØ leading to increased production of the pro-inflammatory cytokine Interleukin-1β (IL-1β). Conversely RNS inhibits inflammasome mediated IL-1β activation, indicating a division between inflammasome activation and RNS production. In the present study MØ from Brown Swiss (BS) cattle produce significantly more RNS and less IL-1β when compared to cells from Holstein Friesian (HF) cattle in response to bacterial or fungal stimuli. Furthermore, BS MØ killed ingested Salmonella typhimurium more efficiently, supporting anecdotal evidence of increased disease resistance of the breed. Inhibition of autophagy by 3-methyladenine (3-MA) stimulated IL-1β secretion in cells from both breeds, but was more pronounced in HF MØ. Blocking RNS production by l-arginase completely abolished RNS production but increased IL-1β secretion in BS MØ. Collectively these preliminary data suggest that the dichotomy of inflammasome activation and RNS production exists in cattle and differs between these two breeds. As pattern recognition receptors and signaling pathways are involved in the assessed functional differences presented herein, our data potentially aid the identification of in vitro predictors of appropriate innate immune response. Finally, these predictors may assist in the discovery of candidate genes conferring increased disease resistance for future use in combination with known production traits., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Increasingly, people diagnosed with cancer are surviving and continuing to participate in the work force. This trend brings with it new issues regarding survivors' employment-related needs., Objective: The research team's objective is to explore cancer survivors' employment-related needs and supports with the ultimate goal of developing a training intervention for them., Methods: Data were collected via an online survey. This article reports on the findings from the pilot stage of the study, which included 32 respondents., Results: Many cancer survivors experience cancer symptoms at work, but do not tend to seek reasonable accommodations. Levels of awareness of possible programmatic and legal supports are low. Respondents reported that neither employers nor medical practitioners are primary sources of information regarding their individual employment-related concerns. Instead, they relied on general information from cancer advocacy organizations., Conclusions: Survivors, employers, and practitioners who treat cancer patients could benefit from training resources about how survivors might address their employment-related needs.

Background: Regular physical activity, even at modest intensities, is associated with many health benefits. Most Americans, however, do not engage in the recommended levels. As practitioners seek ways to increase population rates of physical activity, interventions and advocacy efforts are being targeted to the community level. Yet, advocates, community leaders, and researchers lack the tools needed to assess local barriers to and opportunities for more active, healthy lifestyles. Investigators used a systematic review process to identify key indicators of activity-friendly communities that can assess and improve opportunities for regular physical activity., Methods: Investigators conducted a comprehensive literature review of both peer-reviewed literature and fugitive information (e.g., reports and websites) to generate an initial list of indicators for review (n=230). The review included a three-tiered, modified Delphi consensus-development process that incorporated input of international, national, state, and local researchers and practitioners from academic institutions, federal and state government agencies, nonprofit organizations, and funding agencies in public health, transportation, urban planning, parks and recreation, and public policy., Results: Ten promising indicators of activity-friendly communities were identified: land use environment, access to exercise facilities, transportation environment, aesthetics, travel patterns, social environment, land use economics, transportation economics, institutional and organizational policies, and promotion., Conclusions: Collaborative, multidisciplinary approaches are underway to test, refine, and expand this initial list of indicators and to develop measures that communities, community leaders, and policymakers can use to design more activity-friendly community environments.

It has been 5 years since one of the most important civil rights laws was enacted. The Americans with Disabilities Act (ADA), signed into law on July 26, 1990, was passed to give individuals with disabilities the 'opportunity to compete on an equal basis and to pursue those opportunities for which our free society is justifiably famous…' Because the discrimination faced by people with disabilities is unique in many aspects, the Act is comprehensive and detailed. The obligation not to discriminate against individuals with disabilities, as with people from other minority groups, is placed on society. As a result of these precepts, and the specific measures they entail, the ADA has become the subject of heated debate. The role of government in enacting this type of legislation is questioned as are many aspects of the act itself. The authors of this piece debate the legitimacy of the ADA from an ethical perspective. In addition, they evaluate the values inherent in some of the cases that have come down under the ADA. They conclude that the Act was structured to balance competing interests in order to ensure that the rights of people with disabilities are an important factor in societal decision-making.

Little information exists on the performance of black versus white patients with Alzheimer's disease on neuropsychological tests for dementia. In this study, we compared performance on the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery between white (n = 830) and black (n = 158) patients with Alzheimer's disease enrolled in the CERAD study at 23 university medical centers in the United States. The black patients were older, had fewer years of formal education, and were more impaired in their activities of daily living than were the white patients. After controlling for these characteristics and for duration of the disease and severity of dementia, there were differences in the performance of black and white patients on several of the cognitive measures. Black patients scored lower than whites on tests of visual naming and constructional praxis and on the Mini-Mental State Examination. There were no statistical differences in performance on tests of fluency and word list memory. These findings suggest that cultural or experiential differences may modify performance on specific neuropsychological tests. These factors, in addition to age and educational background, should be considered when interpreting performance on neuropsychological tests in elderly black patients with dementia.

Although extrapyramidal signs such as rigidity, bradykinesia, and postural impairment frequently occur in patients with Alzheimer's disease (AD), the correlation of these parkinsonian manifestations with the neuropathologic changes of Parkinson's disease (PD) has not been well established. Previous clinicopathologic studies addressing this issue have been largely retrospective or have consisted of relatively small numbers of cases. We examined the neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy-confirmed AD prospectively enrolled in the Consortium to Establish a Registry for Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy bodies at any site. There were neocortical Lewy bodies in eight of these 16 cases. Two or more clinical manifestations of extrapyramidal dysfunction were present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62 cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency of neuritic plaques showed no differences between the two groups, neurofibrillary tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and superior temporal cortex (p < 0.05). These findings support previous reports that AD/PD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.

We have characterized the insulin-dependent increase in glucose transport in human adipocytes using subcellular fractionation and antibodies specific for the two isoforms of the glucose transporter that are expressed in these cells. Plasma membranes isolated from untreated human fat cells contain the erythroid/GLUT1 isoform of the glucose transporter almost exclusively whereas the muscle-fat/GLUT4 transporter isoform is most abundant in intracellular microsomal membranes in resting cells. After exposure of adipocytes to insulin, the muscle-fat isoform is dramatically increased in the plasma membrane whereas the erythroid isoform barely changes in response to insulin. Thus, the total insulin-mediated increase in plasma membrane glucose transporters, confirmed by affinity labeling of both transporter isoforms, must be due to the increase in the muscle-fat/GLUT4 transporter. The two isoforms exist in different vesicle populations as shown by immunoadsorption of the muscle fat isoform-containing vesicles which are essentially devoid of the erythroid transporter. These data indicate that the insulin-mediated increases in glucose transport in human fat cells is a result of the translocation of vesicles uniquely containing the muscle-fat glucose transporter isoform.

The Americans with Disabilities Act of 1990 prohibits discrimination against persons with disabilities in employment, government services, public accommodations, public transportation, and telecommunications. This article reviews the impact of the law on the practice of family physicians. Pre-employment medical evaluations are prohibited by law, but medical evaluations may be performed after an offer of employment and before job assignment has been made. Employment may be conditional on results only if medical confidentiality is protected, and exclusionary criteria are job related, applied universally, and do not discriminate against individuals with disabilities. The law provides that persons with disabilities will have equal access to medical care, through prohibiting discrimination based on disability and through the design and construction of medical offices. The law requires physicians who are covered by the law to make reasonable accommodations so that qualified employees and applicants can perform the essential functions of a job.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (greater than 0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.

We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.

We have recently described a monoclonal antibody (1F8) that recognizes a form of glucose transporter unique to fat and muscle (James, D. E., Brown, R., Navarro, J., and Pilch, P. F. (1988) Nature 333, 183-185), tissues that respond acutely to insulin by markedly increasing their glucose uptake. Here, we report that rat adipocytes possess two immunologically distinct glucose-transporters: one recognized by 1F8, and one reactive with antibodies raised against the human erythrocyte glucose transporter. Immunoadsorption experiments indicate that these glucose transporters reside in different vesicle populations and that both transporter isoforms translocate from intracellular sites to the plasma membrane in response to insulin. The insulin-regulatable transporter resides in a unique vesicle that comprises 3% or less of the low density microsomes of fat cells and has a limited protein composition that does not include the bulk of another translocatable protein, the insulin-like growth factor II receptor. Immunoprecipitation with 1F8 of microsomal glucose transporters photoaffinity labeled with [3H]cytochalasin B brings down 90% of the label. Similarly, immunoprecipitation with 1F8 of glucose transporters from insulin-stimulated plasma membranes photolabeled with 3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetyl-f ors kolin, another transporter-selective reagent, results in 75% of the labeled transporter localized in the immunoprecipitate. Thus, insulin action involves the combined effect of translocation from at least two vesicle pools each containing different glucose transporters. The 1F8-reactive transporter comprises the majority of the total transporter pool that is responsible for the insulin-induced increase in glucose transporter number.

Three histochemical techniques for estrogen binding localization in tissue sections were compared to sucrose density gradient analyses for estrogen receptor in 186 breast carcinomas. Apparent localization to epithelial elements was noted using 6-BSA-Fluor-CMO-17 beta-estradiol, 17-BSA-Fluor-TSC-estrogen, and polyestradiol phosphate/anti-estradiol antibody methods. The correlation between the histochemical methods and standard sucrose density gradient techniques was poor for the polyestradiol antibody method and the 6-BSA-fluor-CMO-17 beta-estradiol techniques. While an improved correlation was observed with the 17-BSA-Fluor-TSC-estrogen compound, the compound's binding was not effectively blocked by preincubation with diethylstilbestrol. This failure to show convincing saturability of binding, combined with problems of extraction of soluble receptor proteins in the aqueous incubation media and washed from cells rendered permeable by cryostat sectioning, indicates that several areas will require clarification before histochemical techniques can begin to be considered as a method for estrogen ""receptor" analyses in the clinical evaluation of breast neoplasms.

Post myocardial infarct (MI) patients made significant dietary changed in accordance with the principles of the Prudent Diet. Patients reported changing their intake of selected food items; specifically, consumption of eggs, high-fat meat, whole milk, and butter significantly decreased. A number of food preparation techniques changes, leading to decreases in total fat and saturated fat consumption. Patients reported frying food less, trimming fat from meat, and using more polyunsaturated fat. These changes were unaffected by the length of time since the MI.

Using direct imunofluorescence, lesions from 266 human breast specimens were studied for the presence of IgA, IgM, or IgG localization. The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented, primary breast carcinomas from 153 mastectomy specimens, and 47 biopsies containing metastatic breast cancer. A statistically significant association of IgA and IgM with benign lesions was contrasted to the association of IgG with malignant lesions. In both primary and metastatic lesions, IgG localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers. Among primary breast cancer patients, IgG localization in the tumor correlated with relative lymphopenia. A shorter disease-free interval was noted in association with IgG localization among the metastatic breast lesions. No statistically significant association between stage of disease and immunoglobulin presence was demonstrable. Moderate-to-severe intraductal epithelial hyperplasias were more often associated with immunoglobulin G localization that were other benign lesions.

Brain computed tomographic scans of 60 patients with early-onset Alzheimer's disease (mean age, 60.7 years) were compared with those of age- and sex-matched control subjects. Computed tomographic analysis included standard ventricular measurements as well as subjective ratings of ventricular and sulcal size. These indices were correlated with the results of a battery of neuropsychological tests and electroencephalographic findings. Linear measurements of ventricular size were significantly greater in the patients with Alzheimer's disease than in the age-matched control group (p less than 0.0005). Using subjective appraisal of ventricular and sulcal size, the neuroradiologist noted abnormalities significantly more often in patients than in controls (p less than 0.0005). Linear measurements of ventricular size correlated significantly (p less than 0.05) with the severity of aphasia and dementia and the presence of electroencephalographic abnormalities. There was, however, no correlation between the subjective judgment of cortical atrophy and the degree of impairment as measured by neuropsychological tests. The findings in this study demonstrate the usefulness of computed tomographic imaging in Alzheimer's disease of early onset.