So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases

计量经济分析 = Econometric analysis

The purpose of this Position Stand is to provide guidance to professionals who counsel and prescribe individualized exercise to apparently healthy adults of all ages. These recommendations also may apply to adults with certain chronic diseases or disabilities, when appropriately evaluated and advised by a health professional. This document supersedes the 1998 American College of Sports Medicine (ACSM) Position Stand, "The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness, and Flexibility in Healthy Adults." The scientific evidence demonstrating the beneficial effects of exercise is indisputable, and the benefits of exercise far outweigh the risks in most adults. A program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor exercise training beyond activities of daily living to improve and maintain physical fitness and health is essential for most adults. The ACSM recommends that most adults engage in moderate-intensity cardiorespiratory exercise training for ≥30 min·d on ≥5 d·wk for a total of ≥150 min·wk, vigorous-intensity cardiorespiratory exercise training for ≥20 min·d on ≥3 d·wk (≥75 min·wk), or a combination of moderate- and vigorous-intensity exercise to achieve a total energy expenditure of ≥500-1000 MET·min·wk. On 2-3 d·wk, adults should also perform resistance exercises for each of the major muscle groups, and neuromotor exercise involving balance, agility, and coordination. Crucial to maintaining joint range of movement, completing a series of flexibility exercises for each the major muscle-tendon groups (a total of 60 s per exercise) on ≥2 d·wk is recommended. The exercise program should be modified according to an individual's habitual physical activity, physical function, health status, exercise responses, and stated goals. Adults who are unable or unwilling to meet the exercise targets outlined here still can benefit from engaging in amounts of exercise less than recommended. In addition to exercising regularly, there are health benefits in concurrently reducing total time engaged in sedentary pursuits and also by interspersing frequent, short bouts of standing and physical activity between periods of sedentary activity, even in physically active adults. Behaviorally based exercise interventions, the use of behavior change strategies, supervision by an experienced fitness instructor, and exercise that is pleasant and enjoyable can improve adoption and adherence to prescribed exercise programs. Educating adults about and screening for signs and symptoms of CHD and gradual progression of exercise intensity and volume may reduce the risks of exercise. Consultations with a medical professional and diagnostic exercise testing for CHD are useful when clinically indicated but are not recommended for universal screening to enhance the safety of exercise.

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Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Apparently Healthy Adults: Guidance for Prescribing Exercise

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia (PCA) with meperidine is associated with significantly more neonatal neurobehavioral depression than PCA with morphine. A single dose of epidural morphine (4 mg) decreases postcesarean opioid analgesic requirements and may reduce or prevent neonatal neurobehavioral depression associated with PCA meperidine. Prospectively, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. After umbilical cord clamping, each patient received epidural morphine 4 mg and was randomly allocated to receive either PCA meperidine or PCA morphine. Initial neonatal characteristics, included gestational age, Apgar scores, weight, and umbilical cord gas partial pressures. Brazelton Neonatal Behavioral Assessment Scale (NBAS) examinations were performed on each of the first 4 days of life. Nursing infants (n = 47) were grouped according to maternal PCA opioid in breast milk (meperidine [n = 24] or morphine [n = 23]); bottle-fed infants (n = 56) served as the control group. The three infant groups were equivalent with respect to initial characteristics and NBAS scores on the first 2 days of life. On the third day of life, infants in the morphine group were significantly more alert and oriented to animate human cues compared with infants in the meperidine or control group. On the fourth day of life, infants in the morphine group remained significantly more alert and oriented to animate human auditory cues than infants in the meperidine group. Average PCA opioid consumption through 48 h postpartum was equivalent (0.54 mg/kg morphine and 4.7 mg/kg meperidine); however, even with these small doses, meperidine was associated with significantly poorer neonatal alertness and orientation than morphine. Morphine is the PCA opioid of choice for postcesarean analgesia among nursing parturients. Implications: Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia with meperidine is associated with more neonatal neurobehavioral depression than patient-controlled analgesia with morphine. In this study, we found that nursing infants exposed to morphine were more alert and oriented to animate human cues than those exposed to meperidine. (Anesth Analg 1997;85:600-6)

Postcesarean analgesia using both epidural morphine and intravenous patient-controlled analgesia: neurobehavioral outcomes among nursing neonates

Clinical trials in general surgical journals: Are methods better reported?

Methods: Our objective was to determine public opinionaboutphysiciandisclosureoffinancialincentivesand howthismightbebestcommunicatedtopatients.The2002 General Social Survey included 2765 interviews from a probabilitysampleofEnglish-speakingUShouseholds.The interviewincludedquestionsaboutfinancialincentivesand an audiotaped scenario of a physician discussing the impact of financial incentives on ordering a magnetic resonance image. Respondents heard 1 of 6 randomly selected disclosure strategies. The measurements included ratings of trust, satisfaction, agreement with the physician’sdecision,andlikelihoodofremainingwiththephysician/health plan or seeking a second opinion. Results:Nearlyhalf(48.8%)ofrespondentshadpreviously heard of financial incentives to limit test ordering. Of the respondents,94.8%wantedtobetoldaboutincentives,at thetimeofenrollmentinahealthplan(80.5%),byahealth planrepresentative(44.8%),theirphysician(17.1%),orboth (38.1%).Ofthe6differentdisclosurestrategies,“addressingemotions”and“negotiation”wereassociatedwiththe bestoutcomes,while“commonenemy”and“denyinginfluences” were most negatively perceived. Black and Hispanicsubjectswerelesslikelytoexpresssatisfactionortrust and more likely to disenroll or seek a second opinion. Conclusions:The public wants information about physicianfinancialincentives.Specificcommunicationstyles enhance how this information is conveyed to patients, increasingtrustandsupportingthephysician-patientrelationship.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/486477/IOI40402.pdf

The effect of physician disclosure of financial incentives on trust.

Purpose To evaluate the clinical and pathological features of breast cancer patients who develop contralateral breast cancer (CBC) and assess the impact of the second breast cancer on their prognosis. Patients and methods This retrospective study includes 2136 women with stage I-III breast cancer treated between 1927 and 1987 at the University of Chicago Hospitals. A total of 132 (6.2%) developed CBC during a median follow-up period of 14.2 years; all of them were treated with mastectomy for both breast cancers. We compare the prognostic characteristics, treatments, and outcomes of patients who developed bilateral breast cancer with those who had only unilateral breast cancer (UBC). We also compare the features of the first and the second tumors among patients with bilateral breast cancer (BBC). Results The annual incidence rate for CBC remained constant at an average rate of 0.23%, resulting in a cumulative incidence rate of 6.2%. Patients with BBC were significantly younger than those with UBC (median age, 51 years vs 54 years). No other significant differences were observed between BBC and UBC patients. Among BBC patients, the second cancer was smaller (2.0 cm vs 3.0 cm) and was associated with a lower incidence of axillary node involvement (29% vs 52%). The development of CBC was associated with worse survival (hazard ratio = 1.46 in comparison with patients who did not develop CBC, 95% CI of 1.09-1.95). On multivariate analysis, factors that decreased the disease-specific survival (DSS) in patients with BBC were a higher number of positive lymph nodes of the first and second cancers, a larger size of the second cancer, and a shorter interval between the two primaries. Discussion At the time of diagnosis of first breast cancer, BBC patients were significantly younger than UBC patients. The second cancer among the BBC patients was at an earlier stage than the first one; however, no difference was noticed in the pathological feature between the cancer in the UBC patients and the first cancer of BBC patients. There is an indication that the longer the interval between the two cancers, the better the survival of the BBC patients.

The impact of contralateral breast cancer on the outcome of breast cancer patients treated by mastectomy.

Background Cohort studies have found that short and long sleep are both associated with worse outcomes, compared with intermediate sleep times. While demonstrated biological mechanisms could explain health effects for short sleep, long-sleep risk is puzzling. Most studies reporting the U shape use a single question about sleep duration, a measurement method that does not correlate highly with objectively measured sleep. We hypothesised that the U shape, especially the poor outcomes for long sleepers, may be an artefact of how sleep is measured. Methods We examined the cross-sectional prevalence of fair/poor health by sleep hour categories (≤6, ≤7, ≤8, ≤9, >9 h) in a national US sample of adults aged 62–90 that included several types of sleep measures (n=727). Survey measures were: a single question; usual bedtimes and waking times; and a 3-day sleep log. Actigraphy measures were the sleep interval and total sleep time. Fair/poor health was regressed on sleep hour categories adjusted for demographics, with tests for both linear trend and U shape. Results Adjusted OR of fair/poor health across sleep hour categories from the single question were 4.6, 2.2, referent (8 h), 1.8 and 6.9. There was high prevalence of fair/poor health for ≤6 h for all sleep measures, but the long-sleep effect was absent for sleep logs and actigraphy measures. Conclusions Associations between long sleep and poor health may be specific to studies measuring sleep with survey questions. As cohorts with actigraphy mature, our understanding of how sleep affects health may change.

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Ronald A. Thisted

Papers

Postcesarean analgesia using both epidural morphine and intravenous patient-controlled analgesia: neurobehavioral outcomes among nursing neonates

Clinical trials in general surgical journals: Are methods better reported?

The effect of physician disclosure of financial incentives on trust.

The impact of contralateral breast cancer on the outcome of breast cancer patients treated by mastectomy.

Sleep duration and health among older adults: associations vary by how sleep is measured