Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

First Direct Search for Inelastic Boosted Dark Matter with COSINE-100.

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

Feasibility of a walking workstation to increase daily walking.

OBJECTIVE: The number of calories expended in the workplace has declined significantly in the past 75 years. A walking workstation that allows workers to walk while they work has the potential to increase caloric expenditure. We evaluated whether employees can and will use walking workstations while performing their jobs. METHODS AND PROCEDURES: We studied nurses, clinical assistants, secretaries and appointment secretaries using the StepWatch Activity Monitor System (which accurately measures steps taken at slow speeds) while performing their job functions in their usual fashion and while using the walking workstation. RESULTS: Subjects increased the number of steps taken during the workday by 2000 steps per day (p<0.05). This was equivalent to an increase in caloric expenditure of 100 kcal/day. Subjects reported that they enjoyed using the workstation, that it could be used in the actual work arena and that, if available, they would use it. DISCUSSION: Walking workstations have the potential for promoting physical activity and facilitating weight loss. Several subjects in this study expended more than 200 extra calories daily using such a system. Further trials are indicated.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

The detection of alpha 1-fetoprotein in patients with viral hepatitis.

PIP: Alpha fetoprotein (AFP) was detected in sera (351 samples) of 128 patients with viral hepatitis by radioimmunoassay. 77 positive tests for AFP were obtained. These positive results were demonstrated on 1 or more samples taken from 40 (31%) of the 128 patients studied; the highest value obtained was 4400 ng/ml. Hepatitis B antigen (HBAg) was positive in 26/40 (65%) of patients in whom AFP was detected during the disease process. However, 58/88 (66%) who were seronegative for AFP also demonstrated HBAg in their sera. Chi-square analysis revealed no significant difference in occurrence of detectable AFP between HBAg seropositive and seronegative patients. Individuals seropositive for AFP had no statistically different concentration of the protein than patients seropositive or seronegative for HBAg. 24 patients' sera were tested serially over a 2-week period. Both the peak glutamic-pyruvic transaminase (GPT) and peak total bilirubin levels were in a higher range in those 10/24 patients seropositive (P .001) for AFP than in the 14/24 who were seronegative. Appearance of AFP was related to the severity of liver tissue destruction, as reflected by serum GPT. However, peak AFP levels were attained 5-16 days after peak serum GPT appeared in the circulation.^ieng

Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency.

The usefulness of the red cell distribution width, mean corpuscular volume, and the transferrin saturation in diagnosing iron deficiency anemia were evaluated in a retrospective study of 247 anemic hospitalized patients, many of whom had chronic liver disease. A red cell distribution width greater than 15% had a sensitivity of 71% and a specificity of 54% for iron deficiency as diagnosed by a low serum ferritin or bone marrow examination. A mean corpuscular volume less than 80 femtoliters had a sensitivity of 53% and a specificity of 84%. Transferrin saturation less than 16% had a sensitivity of 61% and a specificity of 86%. Because the sensitivities and specificities of these tests are less than reported in studies of healthier populations, they cannot be relied on for screening for iron deficiency in sick hospitalized patients.

Vasopressin and conditioned flavor aversion in aged rats.

The effect of lysine vasopressin on the performance of young-adult and old rats subjected to a conditioned flavor aversion procedure was studied. Young rats maintained an aversion to a 0.1% saccharin solution significantly longer than did older rats. Treatment with lysine vasopressin ( 1 microgram/kg) during the recovery period prolonged the aversion in both age groups. A single injection of lysine vasopressin prior to the aversion procedure significantly reduced the age difference in extinction. These observations support the hypothesis that age-dependent changes in endogenous vasopressin synthesis or secretion underlie some of the behavioral deficits observed in old animals.

Simple and choice reaction time in dementia: clinical implications.

The present study investigated differences between normal elderly subjects matched for age and education and patients with dementia of the Alzheimer's type (DAT) on two measures of reaction time (RT). Statistically significant group differences clearly demonstrate that normal elderly subjects have faster RT than subjects with senile dementia on all RT tasks. The DAT patients were most clearly differentiated in terms of overall group means and clinical classification from their age-matched counterparts on the choice of RT task. Eleven of 12 (92%) DAT patients displayed choice RT's 2 or more standard deviations above those of age-matched normals. While both RT measures were discriminative between patients and normals, the overall results argue for increased sensitivity when choice is required in RT in accessing the cognitive deficits in DAT.

Evaluation of current criteria used to measure vitamin B12 levels.

Because of recent improvements in the serum vitamin B12 assay, literature criteria based on prior assay methods used in measuring B12 levels were evaluated. Of 1,708 B12 levels measured at Bellevue Hospital in a six-month period, 137 in 124 patients were below 200 pg/ml. Contrary to expectations, 81.6 percent of patients with low B12 levels had a mean corpuscular volume (MCV) below 95 fl. Literature-derived criteria missed 30 percent of patients with low B12 levels. Only three of 12 patients with megaloblastic bone marrow or an abnormal Schilling result had B12 levels that were low (below 100 pg/ml), and nine had values in an intermediate range (100 to 200 pg/ml). This suggests that the use of an MCV below 95 fl and a B12 level below 100 pg/ml as abnormal values may not detect clinically important B12 deficiency.

Drug treatment of the irritable bowel syndrome.

Irritable bowel syndrome (IBS) is defined as a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit, and with features of disordered defecation and distension. The irritable bowel syndrome occurs in 10 to 20% of people worldwide and is very commonly encountered in clinical practice. This has encouraged the pharmaceutical industry to search for effective drug therapy. So far, a universally effective agent has not been found, and since this is a chronic, benign disorder, beginning in youth, long term drug use should be avoided. Nevertheless, if a specific IBS symptom, such as constipation or abdominal pain dominates, a specific drug may be helpful. However, tests and treatment should be minimised or even avoided in order to do no harm. A largely nonpharmaceutical approach to IBS should be taken. This approach employs drugs sparingly and then only targeted at specific and resistant symptoms.

Early recognition and treatment of glucose abnormalities to prevent type 2 diabetes mellitus and coronary heart disease.

Striking parallels exist in both risk and protective factors between coronary heart disease and type 2 diabetes mellitus. Patients with insulin resistance are more likely to develop diabetes and coronary heart disease. Better treatment of diabetes may result in less coronary heart disease, although this has not yet been established. Reliance on fasting glucose determinations alone will overlook a substantial number of patients at risk for diabetes and subsequent coronary heart disease. Measurement of glycosylated hemoglobin should be a routine part of screening for patients at risk for diabetes. Patients with glycosylated hemoglobin levels in the high-normal range should be treated more aggressively with diet, exercise, and medication because evidence is good that diabetes can be prevented (or its onset delayed). Patients with borderline elevations of low-density lipoprotein cholesterol concentrations and with high-normal glycosylated hemoglobin levels should be considered for statin therapy, and patients with hypertension with high-normal glycosylated hemoglobin levels should be treated with angiotensin-converting enzyme inhibitors as first-line agents. Studies to determine whether metformin is useful in this population are ongoing.

The treatment of irritable bowel syndrome.

The efforts of clinical researchers, lay organizations and pharmaceutical companies have increased the public profile of irritable bowel syndrome and made it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical diagnosis, which is the foundation of a logical management strategy. This begins with education. Reassurance that no structural disease threatens should be tempered with the reality that symptoms are likely to recur over many years. Patients expect diet and lifestyle advice, even if this is not specific to irritable bowel syndrome. Only a few of those with irritable bowel syndrome see doctors, and even fewer see specialists. Therefore, the treating physician should ascertain the reason for the visit, the patient's fears and the presence of any comorbid illness, such as depression, that might require treatment in its own right. No drug treatment is useful for all of the symptoms of irritable bowel syndrome, and many patients require no drug at all. If used, drugs should target the predominant symptom. Alosetron, a 5-HT3 antagonist, is effective in treating women with irritable bowel syndrome who also have diarrhoea. Tegaserod, a 5-HT4 agonist, is useful for women with irritable bowel syndrome who are constipated. Most patients with irritable bowel syndrome need psychological support. Reassurance, discussion and relaxation techniques can be provided by the family doctor. Difficult psychopathology may require referral to a mental health professional, and the gastroenterologist can settle diagnostic uncertainties. In all cases, successful treatment depends on a confident diagnosis and the strength of the doctor-patient relationship.

Clinical perspectives, mechanisms, diagnosis and management of irritable bowel syndrome.

This consensus document reviews the current status of the epidemiology, social impact, patient quality of life, pathophysiology, diagnosis and treatment of irritable bowel syndrome. Current evidence suggests that two major mechanisms may interact in irritable bowel syndrome: altered gastrointestinal motility and increased sensitivity of the intestine. However, other factors, such as psychosocial factors, intake of food and prior infection, may contribute to its development. Management of patients is based on a positive diagnosis of the symptom complex, careful history and physical examination to exclude 'red flags' as risk factors for organic disease, and, if indicated, investigations to exclude other disorders. Therapeutic choices include dietary fibre for constipation, opioid agents for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain, although the evidence basis for efficacy is limited or in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing study. Treatment should be tailored to patient needs and fears. Novel therapies are emerging, and drugs acting on serotonin receptors have proven efficacy and a scientific rationale and, if approved, should be useful in the overall management of patients with irritable bowel syndrome. Patient and physician education, early identification of psychosocial issues and better therapies are important strategies to reduce the suffering and societal cost of irritable bowel syndrome.

Cardiovascular complications of inactivity.

Inactivity has a number of consequences for the cardiovascular system. In particular, inactivity can lead to obesity, which can aggravate arthritis. An examination of the effect of exercise on the cardiovascular system requires the review of epidemiologic or population-based studies, because there are no large randomized trials with an exercise control group. Small randomized trials looking at exercise and the individual risk factors are reviewed.

A comparison of work-sampling and time-and-motion techniques for studies in health services research.

OBJECTIVE: This study compares results and illustrates trade-offs between work-sampling and time-and-motion methodologies. DATA SOURCES: Data are from time-and-motion measurements of a sample of medical residents in two large urban hospitals. STUDY DESIGN: The study contrasts the precision of work-sampling and time-and-motion techniques using data actually collected using the time-and-motion approach. That data set was used to generate a simulated set of work-sampling data points. DATA COLLECTION/EXTRACTION METHODS: Trained observers followed residents during their 24-hour day and recorded the start and end time of each activity performed by the resident. The activities were coded and then grouped into ten major categories. Work-sampling data were derived from the raw time-and-motion data for hourly, half-hourly, and quarter-hourly observations. PRINCIPAL FINDINGS: The actual time spent on different tasks as assessed by the time-and-motion analysis differed from the percent of time projected by work-sampling. The work-sampling results differed by 20 percent or more of the estimated value for eight of the ten activities. As expected, the standard deviation decreases as work-sampling observations become more frequent. CONCLUSIONS: Findings indicate that the work-sampling approach, as commonly employed, may not provide an acceptably precise approximation of the result that would be obtained by time-and-motion observations.

The potential for using non-physicians to compensate for the reduced availability of residents.

Both the number of residents and the amount of time existing residents have in which to carry out their activities may soon be decreasing. To consider the potential for alternative ways of staffing teaching hospitals, it is necessary to know how residents spend their time. The authors sought to learn this by conducting a time-motion study of eight internal medicine residents at two urban hospitals in New York City in 1988. The residents' activities were observed and coded by premedical students, and the authors independently classified the possible activities into (1) those that had to be done by a physician, (2) those that were educational only, and (3) those that could be done by a non-physician. A total of 1,726 activities of 67 kinds were coded, averaging 7.75 minutes each. The authors analyze and project their data using two models--the traditional model of care in which the physician is the primary medical manager of the patient, and an alternative model in which a midlevel practitioner, such as a nurse practitioner, would perform the day-to-day monitoring of patients. For example, the data indicate that in the traditional model, almost half of a resident's time is spent in activities that must be done by a physician, meaning that another kind of physician would be needed to do those activities if the resident were unavailable; but in the midlevel practitioner model, only around 20% of the activities would require a physician. The authors give detailed breakdowns of their data, estimate the kinds and numbers of non-physician health care professionals necessary to substitute for residents in appropriate activities, and review possible difficulties in implementing such substitutions.

Gender differences in irritable bowel symptoms.

OBJECTIVE: Some data suggest that the Manning criteria for diagnosis of the irritable bowel syndrome (IBS) are less reliable in men. This research aims to detect gender differences in the prevalence of individual diagnostic criteria in IBS patients. DESIGN: One hundred and fifty-six IBS patients (26 males, 130 females) were asked about their bowel symptoms including the Manning and Rome criteria. RESULTS: In the IBS group, 90.4% fulfilled the Manning criteria (91.5% females, 84.6% males), and 68.6% the Rome criteria (70.8% females and 57.7% males). The three pain-related criteria (pain relieved by defecation, pain followed by change in stool frequency or stool consistency) were similarly present in males and females. However, mucus, feeling of incomplete evacuation, and distension were found in 86 (66.2%), 78 (60%) and 72 (55.4%) of the women, compared to 10 (38%), 7 (26.9%) and 9 (36.9%) of the men (P<0.009, P<0.002 and P=0.053, respectively). Scybala, which are among the Rome criteria, were also less prevalent in males (7.7% vs. 29.2% (P<0.03)). CONCLUSION: Among IBS patients, pain-related Manning symptoms are similar in men and women, but mucus, incomplete evacuation, distension and scybala are less common in men. Less reporting of these symptoms by men may account for reduced clinical reliability of the Manning or Rome criteria in men and their apparent low prevalence of IBS.

Probiotics for irritable bowel syndrome: a light in the darkness?

Probiotics have been used with apparent success for several gut disorders, so it is not surprising they have been tried in the treatment of irritable bowel syndrome (IBS). However, the pathogenesis of this disease is unknown, and opinions about how probiotics might work are speculative. Nevertheless, two small trials suggest they might benefit patients with IBS, particularly those suffering from pain and bloating. This possibility deserves further study. It is important though, that future trials employ criteria-identified subjects, be sufficiently powered and strictly double blind, and select a suitable outcome measure. Until state-of-the-art trials of probiotics are available, their use should remain in the experimental arena.

Irritable bowel syndrome: the view from general practice.

OBJECTIVE: To determine the attributes of the irritable bowel syndrome (IBS) in general practice as perceived by the doctors. SUBJECTS AND METHODS: We administered a 93-item questionnaire about the terminology, diagnosis and treatment of the irritable bowel to 43 of 55 randomly selected general practitioners (28 men, 15 women). RESULTS: General practitioners were unfamiliar with the Manning criteria for the irritable bowel syndrome. Nevertheless, most of them diagnosed the irritable bowel with reasonable confidence and it is less troublesome to them than pelvic pain, headache or backache. Their main concern was excluding organic disease (63%) and 65% believed their patients shared this concern. Nevertheless, they ordered few tests and were often (72%) prepared to make the diagnosis on the initial visit. They estimated that they referred only 14% of IBS patients to specialists, in most cases (56%) because of an unsatisfied patient and in 35% because of an uncertain diagnosis. For treatment, most (77%) chose 'explanation and reassurance'. Virtually all employed drugs, usually several. CONCLUSION: General practitioners say they diagnose the irritable bowel syndrome with less difficulty than other common, painful disorders, but it would be helpful to find out exactly how they do so. Their confidence could be increased by use of diagnostic criteria. Patients referred to specialists are likely to be a minority of hard-to-satisfy people. The optimal approach to such patients should be developed by general practitioners and specialists together. Specialists should strive to satisfy the patient and confirm the diagnosis in the few that are referred. Drug usuage in the irritable bowel syndrome is more than is justified and should, in our view, be minimized.

The management of irritable bowel syndrome: a European, primary and secondary care collaboration.

OBJECTIVE: To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS: Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS: The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS: European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.