Purpose
None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results ...indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC).
Methods
In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1–T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years.
Results
Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (
p
= 0.015), with smaller tumours (
p
= 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%,
p
< 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%,
p
= 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time.
Conclusions
This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials.
Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
Abstract
Purpose
The H-index (H
i
), an author-level metric of scholarly impact, is predictive of future scientific achievement. We sought to analyze the scholarly impact of student authorship on ...the H
i
of corresponding authors (CAs) within a major academic journal in the specialty of ophthalmology.
Materials and Methods
We compared the H
i
of all unique CAs for manuscripts published in
Ophthalmology
(Journal of the American Academy of Ophthalmology) in 2008, 2012, and 2016. Data abstraction was completed twice: in October 2018 and March 2021. We further grouped published articles for CAs into those with student authors (StA) and those without (nStA). Primary analysis involved a linear regression analysis with change in H
i
from October 2018 to March 2021 as the outcome variable, CA groups as the predictor variable, adjusting for the covariates of baseline H
i
, the year when the CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs. Secondary analysis involved a linear regression analysis with change in H
i
from October 2018 to March 2021 as the outcome variable, total number of student authors per CA as the predictor variable, adjusting for the covariates of baseline H
i
, the year CA published his or her article, number of research items published in October 2018, and the academic appointment of the CAs.
Results
The number of student authors increased from 168 in 2008 to 192 in 2016. Of the 902 articles, 316 articles were co-authored by one or more student authors. The average change in H
i
of CAs publishing with student authors (StA, 11.0 ± 14.7) was significantly greater (
p
< 0.0001) than the change in H
i
of CAs publishing without student authors (nStA, 6.2 ± 6.2). As the total number of student authors increased, the change in H
i
of CAs increased linearly for all years combined (regression coefficient = 1.70,
p
-value < 0.0001).
Conclusion
CAs publishing with students in the field of ophthalmology have a higher scholarly impact than those publishing without students. The development of programs to integrate students into ophthalmology research early on may encourage their pursuit of a career in ophthalmology, while advancing the careers of their mentors.
Newly synthesized triglyceride (TG) may exit the liver immediately as VLDL-TG or be stored and secreted after a delay. We quantified the contributions from plasma NEFA, diet, and de novo lipogenesis ...(DNL) to VLDL-TG via immediate and delayed pathways in five lean, normolipidemic subjects; six obese, hypertriglyceridemic (HPTG) nondiabetics; and six obese, HPTG diabetics. Intravenous 2H31palmitate and 1-13C1 acetate and oral 2H35stearate were administered for 30 h preceding an overnight fast. 1,2,3,4-13C4palmitate was infused during the subsequent 12 h fast. Contributions from plasma NEFA via the immediate pathway were 64 ± 15, 33 ± 6, and 58 ± 2% in control, HPTG, and diabetic HPTG, respectively. Delayed pool fractional contributions were as follows: dietary FA, 2.0 ± 0.9, 2.5 ± 1, and 12 ± 2%; DNL, 3 ± 0.3, 14 ± 3, and 13 ± 4%; delayed NEFA, 15 ± 4, 20 ± 4, and 30 ± 3%. VLDL-TG production rates and absolute input rates from the delayed pool were significantly higher in HPTG and diabetic HPTG than in controls. In conclusion, we provide direct kinetic evidence for a hepatic TG storage pool in humans and document its metabolic sources. The turnover time and sources of this pool differ in diabetic HPTG and nondiabetic HPTG, with potential therapeutic implications.
Background
Recruitment of brown adipose tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown adipose ...tissue in humans are unknown.
Case report
In the present paper, we report a case of massive brown adipose tissue infiltration of the visceral adipose tissue depot in a person with Type 2 diabetes with a catecholamine‐secreting paraganglioma. The patient was evaluated with 18F‐fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre‐therapy, during α‐blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous adipose tissue were obtained and evaluated for brown adipose tissue. At diagnosis, brown adipose tissue glucose uptake, assessed by 18F‐fludeoxyglucose‐positron emission tomography, was massively increased. 18F‐fludeoxyglucose uptake was confined to known locations for brown adipose tissue, with additional uptake in the visceral adipose tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2‐kg weight gain.
Conclusion
These results show that human visceral adipose tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown adipose tissue activity, with a doubling of resting energy expenditure.
Congruence, defined as how closely the opinions of politicians match the policy preferences of voters, is a crucial aspect with respect to political legitimacy since a fundamental objective of ...democracy is to provide citizens with the policies they want. Yet there are not many studies that have analyzed the extent citizens and politicians are congruent when it comes to the field of transport. By studying transportation policy priorities of politicians and citizens concerning the use of (i) restrictive instruments and (ii) public transport instruments, this article contributes to the literature in at least three ways. First, the results illustrate how the priority of transportation policies varies between politicians and citizens. Politicians tend to prioritize restrictive measures more so than citizens whereas citizens tend to prioritize a reduction of public transport fares higher than politicians. Second, the article shows how the priority given transportation policy instruments is highly dependent on political ideology. Politicians representing parties to the center or left tend to prioritize the use of restrictive measures higher than politicians representing conservative parties. Third, the article explores whether there is a relationship between transportation policy congruence and political legitimacy. The article shows that lack of congruence is associated with a reduced level of trust towards local politicians and citizens being less likely to support local regime principles. These are important findings inasmuch as the literature suggests that lack of political support potentially make citizens more likely to call for radical changes, demonstrate and even abstain from the political process altogether.
Stamping of sheet metal components without lubrication or using minimum amount of hazard free lubricant is a possible solution to diminish health hazards to personnel and environmental impact and to ...reduce production costs. This paper studies the application of diamond-like coating (DLC) under severe lubrication conditions by adopting strip reduction testing to replicate industrial ironing production of deep drawn, stainless steel cans. Three DLC coatings are investigated; multi-layer, double layer and single layer. Experiments revealed that the double layer coating worked successful, i.e. with no sign of galling using no lubrication even at elevated tool temperature, while the other two coatings peeled off and resulted in severe galling unless lubrication was applied.
Summary
Background Primary hyperparathyroidism (PHPT) is associated with reduced bone mineral density (BMD) mainly at sites rich in cortical bone. However, successful parathyroidectomy causes an ...increase in BMD especially at sites rich in trabecular bone. Plasma 25‐hydroxyvitamin D (25OHD) levels are typically reduced and plasma 1,25‐dihydroxyvitamin D 1,25(OH)2D slightly increased in PHPT. These variations in vitamin D metabolites may influence variations in BMD and fracture risk.
Aim To investigate relations between preoperative vitamin D metabolites and skeletal consequences in patients with untreated PHPT and to appraise the influence of preoperative vitamin D metabolites on postoperative changes in BMD.
Design Cross‐sectional and cohort study.
Materials Two hundred and forty‐six consecutive Caucasian PHPT patients aged 19–91 years. (median 63, 87% females).
Results BMD was reduced at the femoral neck (P < 0·001) and forearm (P < 0·001), but normal at the lumbar spine (P = 0·11). Levels of biochemical bone markers were associated with high plasma PTH, high plasma 1,25(OH)2D and low plasma levels of 25OHD. Moreover, low plasma 25OHD was associated with low levels of BMD at the femoral neck (rp = 0·23), the forearm (rp = 0·19) and the whole body (rp = 0·30), whereas plasma 1,25(OH)2D was inversely associated with BMD at all regional sites and the whole body. Plasma PTH only showed an inverse association with BMD at the forearm (rp = –0·21). No association was observed between biochemical variables and prevalent spinal fractures, all peripheral fractures or osteoporotic peripheral fractures. The annual increase in spinal BMD after surgery was positively associated with preoperative plasma PTH (rp = 0·40), whereas the annual increase in whole body BMD was inversely associated with plasma 25OHD (rp = –0·32). No change in BMD at the femoral neck and forearm was observed 1 year after surgery.
Conclusion Low vitamin D status and high plasma 1,25(OH)2D are associated with increased bone turnover and decreased BMD in patients with PHPT.
We report a case of a newborn with unilateral retinal detachment that could not be repaired. At examination under anesthesia, the retina was markedly abnormal and a presumptive diagnosis of retinal ...dysplasia was made. Several years later, the eye was enucleated because it was blind and painful. Final pathology was consistent with familial exudative vitreoretinopathy (FEVR). The literature describing unilateral retinal dysplasia is sparse. This case adds to the clinical spectrum of pathologic findings in FEVR.
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