Aims/hypothesis
Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, ...we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
Methods
A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.
Results
A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.
Conclusions/interpretation
Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.
Summary
We pilot-tested a trial of home exercise on individuals with osteoporosis and spine fracture.
Our target enrollment was met, though it took longer than expected. Participants stayed in the ...study and completed the exercise program with no safety concerns.
Future trials should expand the inclusion criteria and consider other changes.
Purpose
Osteoporotic fragility fractures create a substantial human and economic burden. There have been calls for a large randomized controlled trial examining the effect of exercise on fracture incidence. The B3E pilot trial was designed to evaluate the feasibility of a large trial examining the effects of home exercise on individuals at high risk of fracture.
Methods
Community-dwelling women ≥ 65 years with radiographically confirmed vertebral compression fractures were recruited at seven sites in Canada and Australia. We randomized participants in a 1:1 ratio to a 12-month home exercise program or equal attention control group, both delivered by a physiotherapist (PT). Participants received six PT home visits in addition to monthly phone calls from the PT and a blinded research assistant. The primary feasibility outcomes of the study were recruitment rate (20 per site in 1 year), retention rate (75% completion), and intervention adherence rate (60% of weeks meeting exercise goals). Secondary outcomes included falls, fractures and adverse events.
Results
One hundred forty-one participants were recruited; an average of 20 per site, though most sites took longer than anticipated. Retention and adherence met the criteria for success: 92% of participants completed the study; average adherence was 66%. The intervention group did not differ significantly in the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR 1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious adverse events in the intervention group and 12 in the control group.
Conclusion
An RCT of home exercise in women with vertebral fractures is feasible but recruitment was a challenge. Suggestions are made for the conduct of future trials.
Summary
Due to limitations of the predominant clinical method for diagnosing osteoporosis, an engineering model based on a dedicated CT scanner for bone density and structure was applied in fracture ...patients and controls. Improved diagnostic performance was observed, which supports its potential use in future research and clinical practice.
Introduction
Dual-energy X-ray absorptiometry (DXA), the predominant clinical method for diagnosing osteoporosis, has limitations in identifying individuals with increased fracture risk. Peripheral quantitative computed tomography (pQCT) provides additional information and can be used to generate finite element (FE) models from which bone strength properties can be estimated. We investigated the ability of pQCT-FE properties to distinguish peripheral low-trauma fracture patients from healthy controls, by comparison with DXA and standard pQCT.
Methods
One hundred and eight fracture patients (77 females aged 67.7 ± 7.9 years, 31 males aged 69.7 ± 8.9 years) were recruited from a hospital fracture liaison service. One hundred and twenty healthy community controls (85 females aged 69.8 ± 8.5 years, 35 males aged 68.9 ± 7.2 years) were recruited.
Results
Significant differences between groups were observed in pQCT-FE properties, especially at the 4% tibia site. Fracture odds increased most per standard deviation decrease in pQCT-FE at this location shear stiffness estimate,
k
shear
, in females, OR = 10.34, 95% CI (1.91, 43.98); bending stiffness estimate,
k
bend
, in males, OR = 8.32, 95% CI (4.15, 33.84). Area under the receiver operating characteristics curve (AUROC) was observed to be highest with pQCT-FE properties at 4% the tibia site. In females, this was 0.83 for the pQCT-FE variable
k
shear
, compared with 0.72 for DXA total hip bone density (TH aBMD) and 0.76 for pQCT tibia trabecular density (Trb vBMD); in males, this was 0.81 for the pQCT-FE variable
k
bend
at the 4% tibia site, compared with 0.62 for TH aBMD and 0.71 for Trb vBMD. There were significant differences in AUROC between DXA and pQCT-FE variables in both females (
p
= 0.02) and males (
p
= 0.03), while no difference was observed in AUROC between primary pQCT and pQCT-FE variables.
Conclusions
pQCT-FE modeling can provide enhanced diagnostic performance compared with DXA and, given its moderate cost, may be useful in clinical settings.
Summary
Prophylactic oophorectomy is recommended for women at high risk for ovarian cancer, but the associated impact on bone health is of clinical concern. This prospective, controlled study ...demonstrated substantial loss of bone density and bone strength following surgical menopause. Postoperative hormone therapy alleviated, but not fully prevented, spinal bone loss.
Introduction
This prospective study investigated bone health in women following premenopausal oophorectomy.
Methods
Dual-energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and pQCT-based finite element analysis (pQCT-FEA) were used to assess bone health between systemic hormone therapy (HT) users and non-users after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared with premenopausal controls over 24-month follow-up.
Results
Mean age was 42.4 ± 2.6 years (
n
= 30) for the surgery group and 40.2 ± 6.3 years for controls (
n
= 42), and baseline bone measures were similar between groups. Compromised bone variables were observed at 24 months after RRBSO, among which areal bone mineral density (aBMD) at the lumbar spine, tibial volumetric cortical density (Crt vBMD), and tibial bending stiffness (
k
bend
) had decreased by 4.7%, 1.0%, and 12.1%, respectively (all
p
< 0.01). In non-HT users, significant losses in lumbar spine (5.8%), total hip (5.2%), femoral neck (6.0%) aBMD, tibial Crt vBMD (2.3%), and
k
bend
(14.8%) were observed at 24 months (all
p
< 0.01). HT prevented losses in
k
bend
, tibial Crt vBMD, and aBMD, except for modest 2.3% loss at the lumbar spine (
p
= 0.01).
Conclusion
This prospective, controlled study of bone health following RRBSO or premenopausal oophorectomy demonstrated substantial loss of bone density and bone strength following RRBSO. HT prevented loss of bone density and bone stiffness, although there was still a modest decrease in lumbar spine aBMD in HT users. These findings may inform decision-making about RRBSO and clinical management following premenopausal oophorectomy.
The global positioning system (GPS) is increasingly being used to monitor animal movement and to develop more sustainable land management practices. Reliable and accurate GPS data are required to ...develop robust animal resource selection functions (RSFs). This study used Earth Centred Earth Fixed (ECEF) high fix rate (4
Hz) GPS data collected from Fleck™ 2 GPS collars fitted to six cows over a four-day period. The GPS data were used to derive speed and mean speed histograms. Maximum mean speed values were used to model the maximum distance travelled for a range of sample intervals. Maximum distance travelled was used to estimate the minimum area that could be predicted. To extend the methods further, we explored the use of probability density functions to describe the speed profiles; a Gamma probability density function (PDF) was shown to provide the best description. By modelling animal speeds using both the raw data and the PDF, it was possible to estimate the minimum area occupied for varying GPS sample frequencies and patch areas. Overall, the cows spent the greatest proportion (77%) of their time either stationary or moving very slowly (less than 0.2
m
s
−1). Despite the slow speeds, the prediction errors were around 90% for sample frequencies of greater than half an hour and a patch area of 100
m
2. If study patch areas are between 10 and 100
m
2 the GPS fix rate would need to be less than 10
s. When GPS fix intervals are recorded at 1
h intervals, the probability of accurately predicting selection within a 10
000
m
2 patch is approximately 30%. Researchers and land managers that use GPS technology to monitor animal behaviour should be aware of the relationship between GPS fix rate and accuracy in predicting landscape use especially when attempting to develop resource selection functions. One approach to using low GPS fix rates would be to gather short duration, high fix rate GPS data to derive speed histograms for establishing probability density functions. These speed histograms could then be used in conjunction with the low fix rate data to establish the probability of an animal visiting a given patch within a landscape.
The study described in this paper developed a model of animal movement, which explicitly recognised each individual as the central unit of measure. The model was developed by learning from a real ...dataset that measured and calculated, for individual cows in a herd, their linear and angular positions and directional and angular speeds. Two learning algorithms were implemented: a Hidden Markov model (HMM) and a long-term prediction algorithm. It is shown that a HMM can be used to describe the animal's movement and state transition behaviour within several “stay” areas where cows remained for long periods. Model parameters were estimated for hidden behaviour states such as relocating, foraging and bedding. For cows’ movement between the “stay” areas a long-term prediction algorithm was implemented. By combining these two algorithms it was possible to develop a successful model, which achieved similar results to the animal behaviour data collected. This modelling methodology could easily be applied to interactions of other animal species.
Tests on B−L symmetry breaking models are important probes to search for new physics. One proposed model with Δ(B−L)=2 involves the oscillations of a neutron to an antineutron. In this paper, a new ...limit on this process is derived for the data acquired from all three operational phases of the Sudbury Neutrino Observatory experiment. The search concentrated on oscillations occurring within the deuteron, and 23 events were observed against a background expectation of 30.5 events. These translated to a lower limit on the nuclear lifetime of 1.48×1031 yr at 90% C.L. when no restriction was placed on the signal likelihood space (unbounded). Alternatively, a lower limit on the nuclear lifetime was found to be 1.18×1031 yr at 90% C.L. when the signal was forced into a positive likelihood space (bounded). Values for the free oscillation time derived from various models are also provided in this article. This is the first search for neutron-antineutron oscillation with the deuteron as a target.
The long baseline between Earth and the Sun makes solar neutrinos an excellent test beam for exploring possible neutrino decay. The signature of such decay would be an energy-dependent distortion of ...the traditional survival probability which can be fit for using well-developed and high-precision analysis methods. Here a model including neutrino decay is fit to all three phases of B8 solar neutrino data taken by the Sudbury Neutrino Observatory (SNO). This fit constrains the lifetime of neutrino mass state ν2 to be >8.08×10−5 s/eV at 90% confidence. An analysis combining this SNO result with those from other solar neutrino experiments results in a combined limit for the lifetime of mass state ν2 of >1.92×10−3 s/eV at 90% confidence.
Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells ...(BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 95% CI, 3.9-100.3). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction ( r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.
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