Analytic and Bootstrap-after-Cross-Validation Methods for Selecting Penalty Parameters of High-Dimensional M-Estimators

We develop two new methods for selecting the penalty parameter for the $\ell^1$-penalized high-dimensional M-estimator, which we refer to as the analytic and bootstrap-after-cross-validation methods. For both methods, we derive nonasymptotic error bounds for the corresponding $\ell^1$-penalized M-estimator and show that the bounds converge to zero under mild conditions, thus providing a theoretical justification for these methods. We demonstrate via simulations that the finite-sample performance of our methods is much better than that of previously available and theoretically justified methods.Comment: 63 pages, 6 figure

Data-Driven Tuning Parameter Selection for High-Dimensional Vector Autoregressions

Lasso-type estimators are routinely used to estimate high-dimensional time series models. The theoretical guarantees established for Lasso typically require the penalty level to be chosen in a suitable fashion often depending on unknown population quantities. Furthermore, the resulting estimates and the number of variables retained in the model depend crucially on the chosen penalty level. However, there is currently no theoretically founded guidance for this choice in the context of high-dimensional time series. Instead one resorts to selecting the penalty level in an ad hoc manner using, e.g., information criteria or cross-validation. We resolve this problem by considering estimation of the perhaps most commonly employed multivariate time series model, the linear vector autoregressive (VAR) model, and propose a weighted Lasso estimator with penalization chosen in a fully data-driven way. The theoretical guarantees that we establish for the resulting estimation and prediction error match those currently available for methods based on infeasible choices of penalization. We thus provide a first solution for choosing the penalization in high-dimensional time series models.Comment: 54 pages, 2 figure

Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.

BACKGROUND: Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation. OBJECTIVE: To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation. METHODS: Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review. RESULTS: We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors. LIMITATIONS: Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data. CONCLUSION: Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low

Disparities in the access to atrial fibrillation ablation in Denmark:who gets ablated, who neglected?

Aims: Atrial fibrillation (AF) is a common arrhythmia associated with reduced quality of life that can lead to serious complications such as stroke and heart failure. Ablation is a safe and effective treatment for AF but is not offered equally to all patients. The aim of this study is to identify demographic groups more or less likely to undergo AF ablation. Methods and results: All patients with newly diagnosed AF between 2010 and 2018 were identified in the Danish nationwide registries. The association between gender, age, level of education and attachment to the job market, and the likelihood of receiving AF ablation was investigated using multivariable Cox proportional hazard analysis. Cumulative incidence was calculated using the Aalen-Johansen estimator. A total of 176 248 patients were included. Men were more likely to receive ablation than women (7% vs. 3%). Patients aged 25-44 and 45-64 were most likely to receive ablation, while only 0.7% of patients aged 80 or above received ablation. The rate of ablation significantly decreased with decreasing level of education. Full-time employed patients were most likely to receive ablation, followed by self-employed, unemployed, on sick leave, undergoing education, and early retired patients. Retired patients were the least likely to receive ablation (3%). Conclusion: This study found that women, older patients, patients with lower levels of education, and patients on social benefits are less likely to receive AF ablation. These findings suggest that there are significant social and economic disparities in AF ablation treatment in Denmark.</p

A review on broodstock nutrition of marine pelagic spawners: the curious case of the freshwater eels (Anguilla spp.)

To sustain eel aquaculture, development of reproduction in captivity is vital. The aim of this review is to assess our current knowledge on the nutrition of broodstock eels in order to improve the quality of broodstock under farming conditions, drawing information from wild adult eels and other marine pelagic spawners. Freshwater eels spawn marine pelagic eggs with an oil droplet (type II), and with a large perivitelline space. Compared with other marine fish eggs, eel eggs are at the extreme end of the spectrum in terms of egg composition, even within this type II group. Eel eggs contain a large amount of total lipids, and a shortage of neutral lipids has been implied a cause for reduced survival of larvae. Eel eggs have higher ARA but lower EPA and DHA levels than in other fish. Too high levels of ARA negatively affected reproduction in the Japanese eel, although high levels of 18:2n-6 in the eggs of farmed eels were not detrimental. The total free amino acid amount and profile of eel eggs appears much different from other marine pelagic spawners. Nutritional intervention to influence egg composition seems feasible, but responsiveness of farmed eels to induced maturation might also require environmental manipulation. The challenge remains to succeed in raising European eel broodstock with formulated feeds and to enable the procurement of viable eggs and larvae, once adequate protocols for induced maturation have been developed

Obesity, Type 2 Diabetes and Bone in Adults.

In an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges in fracture prediction in obesity and T2DM. Dual energy X-ray absorptiometry underestimates risk, standard clinical risk factors may not capture all relevant information, and risk is under-recognised by clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients

Understanding the incidence of atrial fibrillation and stroke in hypertrophic cardiomyopathy patients:insights from Danish nationwide registries

Aims The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors. Methods and results Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen–Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08–1.63], hypertension (HT) (HR 1.36, 95% CI 1.14–1.67), and obstructive HCM (HR 1.27, 95% CI 1.05–1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18–0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis. Conclusion Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC.</p