Calcium metabolism and breast cancer risk

Emerging evidence suggests that calcium and its regulating hormones, i.e. vitamin D and parathyroid hormone (PTH), affect breast cancer risk. The associations between serum calcium levels and breast cancer risk, between serum calcium levels and known risk factors of breast cancer, and between serum calcium levels and breast cancer aggressiveness were examined within the Malmö Preventive Project, a population-based cohort comprising 10,902 women. Serum calcium, 25-hydroxyvitamin D (25OHD) and PTH-levels were furthermore examined in relation to breast cancer risk in a nested case-control study comprising 764 breast cancer cases within the Malmö Diet and Cancer Study. Serum calcium levels were positively associated with breast cancer risk in overweight/obese women. In premenopausal women, serum calcium was in one study negatively, and in one study positively, associated with breast cancer. Calcium was positively associated with breast cancer aggressiveness in overweight and/or premenopausal women. Premenopausal status and use of oral contraceptives and hormone-replacement therapy were negatively associated with serum calcium levels. BMI was significantly associated with serum calcium levels, with lean and overweight women having higher calcium levels than women with BMI between 20 and 25. There was a weak, statistically non-significant, inverse association between 25OHD-levels and breast cancer risk. There was no evidence for any relation between PTH-levels and breast cancer. It is concluded that serum calcium is positively associated with breast cancer risk and aggressiveness in overweight women. There may be a weak negative association between vitamin D and breast cancer risk, but this will have to be further examined

Multi-level local time-stepping methods of Runge-Kutta type forwave equations

Local mesh refinement significantly in uences the performance of explicit time-stepping methods for numerical wave propagation. Local time-stepping (LTS) methods improve the efficiency by using smaller time-steps precisely where the smallest mesh elements are located, thus permitting a larger time-step in the coarser regions of the mesh without violating the stability condition. However, when the mesh contains nested patches of refinement, any local time-step will be unnecessarily small in some regions. To allow for an appropriate time-step at each level of mesh refinement, multi-level local time-stepping (MLTS) methods have been proposed. Starting from the Runge{Kutta-based LTS methods derived by Grote et al. [17], we propose explicit MLTS methods of arbitrarily high accuracy. Numerical experiments with finite difference and continuous finite element spatial discretizations illustrate the usefulness of the novel MLTS methods and show that they retain the high accuracy and stability of the underlying Runge{Kutta methods

Adjoint-based inversion for stress and frictional parameters in earthquake modeling

We present an adjoint-based optimization method to invert for stress and frictional parameters used in earthquake modeling. The forward problem is linear elastodynamics with nonlinear rate-and-state frictional faults. The misfit functional quantifies the difference between simulated and measured particle displacements or velocities at receiver locations. The misfit may include windowing or filtering operators. We derive the corresponding adjoint problem, which is linear elasticity with linearized rate-and-state friction with time-dependent coefficients derived from the forward solution. The gradient of the misfit is efficiently computed by convolving forward and adjoint variables on the fault. The method thus extends the framework of full-waveform inversion to include frictional faults with rate-and-state friction. In addition, we present a space-time dual-consistent discretization of a dynamic rupture problem with a rough fault in antiplane shear, using high-order accurate summation-by-parts finite differences in combination with explicit Runge--Kutta time integration. The dual consistency of the discretization ensures that the discrete adjoint-based gradient is the exact gradient of the discrete misfit functional as well as a consistent approximation of the continuous gradient. Our theoretical results are corroborated by inversions with synthetic data. We anticipate that adjoint-based inversion of seismic and/or geodetic data will be a powerful tool for studying earthquake source processes; it can also be used to interpret laboratory friction experiments.Comment: Updated title, added additional references, provided additional details in sections 1 and 5, fixed typo

Hyperparathyroidism and new onset diabetes after renal transplantation.

Secondary hyperparathyroidism persists after renal transplantation in a substantial number of patients. Primary hyperparathyroidism and secondary hyperparathyroidism are both associated with abnormalities in glucose metabolism, such as insufficient insulin release and glucose intolerance. The association of hyperparathyroidism and diabetes after renal transplantation has, as far as we know, not been studied. Our aim was to investigate whether hyperparathyroidism is associated with new-onset diabetes mellitus after transplantation (NODAT) during the first year posttransplantation

Delays in the Management of Retroperitoneal Sarcomas

Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal sarcoma in the southern Sweden health care region 2003–2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23 days (0–17 months) and median health care delay of 94 days (1–40 months) with delays of median 15 days at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers and indicate that development of coordinated diagnostic packages could shorten delays at the sarcoma centre

Total thyroidectomy: reduction in postoperative hypoparathyroidism

Objective: Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy oper ations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease. Design: Retrospective cohort study from a single institution. Methods: We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease. Results: We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021. Conclusion: Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery. Significance statement: Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoper ative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures