This paper describes the core features of the R package geepack, which implements the generalized estimating equations (GEE) approach for fitting marginal generalized linear models to clustered data. Clustered data arise in many applications such as longitudinal data and repeated measures. The GEE approach focuses on models for the mean of the correlated observations within clusters without fully specifying the joint distribution of the observations. It has been widely used in statistical practice. This paper illustrates the application of the GEE approach with geepack through an example of clustered binary data.

When testing for reduction of the mean value structure in linear mixed models, it is common to use an asymptotic χ 2 test. Such tests can, however, be very poor for small and moderate sample sizes. The pbkrtest package implements two alternatives to such approximate χ 2 tests: The package implements (1) a Kenward-Roger approximation for performing F tests for reduction of the mean structure and (2) parametric bootstrap methods for achieving the same goal. The implementation is focused on linear mixed models with independent residual errors. In addition to describing the methods and aspects of their implementation, the paper also contains several examples and a comparison of the various methods.

OBJECTIVEThe role of telemedical monitoring in diabetic foot ulcer care is still uncertain. Our aim was to compare telemedical and standard outpatient monitoring in the care of patients with diabetic foot ulcers in a randomized controlled trial. RESEARCH DESIGN AND METHODSOf the 736 screened individuals with diabetic foot ulcers, 401 met the eligibility criteria and were randomized between October 2010 and November 2014. The per-protocol telemedical monitoring consisted of two consultations in the patient's own home and one consultation at the outpatient clinic. Standard practice consisted of three outpatient clinic visits. The three-visit cycle was repeated until study end point. The study end points were defined as complete ulcer healing, amputation, or death. RESULTSOne hundred ninety-three individuals were randomized to telemedical monitoring and 181 to standard care. Demographics were similar in both groups. A causespecific Cox proportional hazards model showed no difference in individuals monitored through telemedicine regarding wound healing (hazard ratio 1.11 [95% CI 0.87, 1.42], P = 0.42) or amputation (0.87 [0.54, 1.42], P = 0.59). We found a higher mortality incidence in the telemedical monitoring group compared with the standard outpatient monitoring group (8.68 [6.93, 10.88], P = 0.0001). CONCLUSIONSThe findings of no significant difference regarding amputation and healing between telemedical and standard outpatient monitoring seem promising; however, for telemedical monitoring, a higher mortality throws into question the role of telemedicine in monitoring diabetic foot ulcers. Further studies are needed to investigate effects of telemedicine on mortality and other clinical outcomes and to identify patient subgroups that may have a poorer outcome through telemedical monitoring.Diabetes currently affects .387 million people worldwide, and this number is expected to rise to .592 million individuals worldwide by 2035 (1). In Denmark, 320,545 people suffer from diabetes, and it is estimated that a further 200,000 individuals are undiagnosed; a further 750,000 have impaired glucose tolerance (2). Approximately 7-15% of the population with diabetes will have one or several foot ulcers during a lifetime, and up to 70% of these ulcers will recur during a 5-year period (3). Diabetic foot ulcers lead to ;500 major amputations every year in

The multielemental composition of organic and conventional winter wheat, spring barley, faba bean, and potato was analyzed with inductively coupled plasma-optical emission spectrometry (ICP-OES) and -mass spectrometry (ICP-MS). The crops were cultivated in two years at three geographically different field locations, each accommodating one conventional and two organic cropping systems. The conventional system produced the highest harvest yields for all crops except the nitrogen-fixing faba bean, whereas the dry matter content of each crop was similar across systems. No systematic differences between organic and conventional crops were found in the content of essential plant nutrients when statistically analyzed individually. However, chemometric analysis of multielemental fingerprints comprising up to 14 elements allowed discrimination. The discrimination power was further enhanced by analysis of up to 25 elements derived from semiquantitative ICP-MS. It is concluded that multielemental fingerprinting with semiquantitative ICP-MS and chemometrics has the potential to enable authentication of organic crops.

The aim of this study was to investigate the effects of social contact and milk allowance on social behavior, play behavior, and responses to handling in dairy calves. Forty test calves and 16 companion calves were allocated to 1 of 5 treatments from birth to 4 wk of age: (1) housed singly and fed 5 L of milk/d; (2) housed singly and fed 9 L of milk/d; (3) housed in pairs and fed 5 L of milk/d; (4) housed in pairs and fed 9 L of milk/d; or (5) kept with the dam and fed 9 L of milk/d. From 4 to 6 wk of age, all calves were offered 5 L of milk/d to promote intake of solid feed before weaning. At 6 wk of age, all calves were weaned, and at 7 wk of age, they were grouped (7 calves/group: 1 test calf from each treatment and 2 companion calves). The response to restraint during blood sampling was recorded weekly; singly housed calves struggled more during restraint than did calves kept with the dam, and pair-housed calves struggled at an intermediate level. Play behavior was recorded for 20 min/wk after the provision of fresh straw; calves housed singly and fed a low milk allowance spent less time playing than did calves in all other treatments. Three days after grouping, calves were subjected to a feed competition test; calves receiving the high milk allowance and housed in pairs spent more time feeding than did those receiving the high milk allowance and housed singly, with all other treatments showing intermediate responses. These results indicate that social contact decreased responses to restraint and increased play and competitive success. The high milk allowance increased play but reduced competitive success after grouping. Lower responses to restraint indicated less responsiveness to stress. Play is considered an indicator of positive welfare, and competitive success helps calves succeed in a group environment.

In swine nutrition, little is known about the vitamin D requirements for reproductive processes and bone health. Consequently, the vitamin D recommendation for sows during gestation and lactation is not based on scientific reports. The current study was undertaken to obtain information on the dose-response pattern of 2 vitamin D sources, the commonly used cholecalciferol, called vitamin D(3), and a newly developed Hy.D product (25-hydroxycholecalciferol). In Exp. 1, a total of 160 gilts were randomly assigned from the first estrus until d 28 of gestation to dietary treatments containing 4 concentrations of 1 of the 2 different vitamin D sources [200, 800, 1,400, and 2,000 IU/kg of vitamin D from cholecalciferol or corresponding doses of 5, 20, 35, and 50 microg/kg of feed from 25(OH)D(3) (Hy.D)]. In a concurrent experiment, the same 8 dietary treatments were provided to 160 multiparous sows from the first day of mating until weaning. Plasma concentrations of 25(OH)D(3) were influenced by a dose x form interaction (P < 0.001); furthermore, plasma 25(OH)D(3) concentrations were influenced by the lactation state of the sows. Irrespective of the dietary dose and form of vitamin D provided to the sows, very little vitamin D was transferred to the progeny. Reproductive performance was not influenced by dietary vitamin D treatments, except for a decreased number of stillborn piglets (P = 0.03, SE = 0.40) with the larger doses of vitamin D (1,400 and 2,000 IU of vitamin D, resulting in 1.17 and 1.13 stillborn piglets per litter, respectively) compared with the smaller doses of vitamin D (200 and 800 IU of vitamin D, resulting in 1.98 and 1.99 stillborn piglets per litter, respectively). In the gilt trial, the ultimate strength of the bones (P = 0.01) and their content of ash (P = 0.02) were greater when vitamin D(3) was supplemented in doses larger than 800 IU, compared with the same amount of Hy.D supplementation. In the sow experiment, lactation day (P < 0.001), rather than dietary vitamin D, influenced the concentrations of osteocalcin and Ca as well as the activities of total alkaline phosphatase and bone alkaline phosphatase in plasma. Age of the suckling piglets affected their plasma bone health markers. In conclusion, at doses greater than 200 IU, Hy.D was more bioavailable than vitamin D(3) and, as such, could be considered an equivalent or even more advantageous source of vitamin D. In addition, a dietary dose of approximately 1,400 IU of vitamin D is recommended for reproducing swine. Irrespective of the dietary dose and form of vitamin D provided to the sows, very little vitamin D was transferred to the progeny.

Background: Family history is an established risk factor for breast cancer. Although some important genetic factors have been identified, the extent to which familial risk can be attributed to genetic factors versus common environment remains unclear.Methods: We estimated the familial concordance and heritability of breast cancer among 21,054 monozygotic and 30,939 dizygotic female twin pairs from the Nordic Twin Study of Cancer, the largest twin study of cancer in the world. We accounted for leftcensoring, right-censoring, as well as the competing risk of death.Results: From 1943 through 2010, 3,933 twins were diagnosed with breast cancer. The cumulative lifetime incidence of breast cancer taking competing risk of death into account was 8.1% for both zygosities, although the cumulative risk for twins whose cotwins had breast cancer was 28% among monozygotic and 20%

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