Overt hypoadrenalism is uncommon in patients with stage 3 and 4 bronchogenic carcinoma

Introduction. Lung cancer is the leading cause of cancer mortality in most countries. The adrenal glands are common sites of metastatic lung cancer as approximately 40% of subjects with stage 4 bronchogenic carcinoma have adrenal metastases. The prevalence of biochemical hypoadrenalism is, however, remarkably poorly documented.Objectives. Our study aimed to determine the prevalence of primary hypoadrenalism, as defined by a subnormal cortisol response to the 250 µg adrenocorticotrophic hormone (ACTH) stimulation test, in patients with stage 3 and 4 lung cancer.Methods. Thirty patients with stage 3 and 4 bronchogenic carcinoma were prospectively recruited from the bronchus clinic. Demographic data and electrolytes were recorded and each patient had a 250 µg ACTH stimulation test to determine the prevalence of overt adrenal insufficiency, defined as a +30 minute cortisol of less than 550 nmol/l.Results. The median age and quartile deviation was 62 (10) years and the median basal cortisol was 429.5 (321) nmol/l. The median peak cortisol was 828.5 (342) nmol/l (range 536 - 1 675 nmol/l). Twenty-eight patients (93.3%) had an appropriate rise of cortisol to greater than 550 nmol/l following 250 µg ACTH stimulation. Two patients (6.7%) had mild primary adrenal failure with a peak cortisol between 500 and 550 nmol/l associated with a raised plasma ACTH concentration (131.4 and 10.5 pmol/l, normal 2.2 - 10 pmol/l). Twenty-eight patients (92.9%) were normonatraemic, while the two hyponatraemic patients had biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion.Conclusion. In conclusion, despite evidence that the adrenal glands of patients with disseminated bronchogenic carcinoma are frequently affected by metastatic disease, biochemical evidence of clinically significant hypoadrenalism is relatively uncommon and is not accurately predicted by electrolyte abnormalities

Relationships between traditional and fundamental dough-testing methods

Two fundamental test systems were used to evaluate the visco-elastic properties of doughs from wheat samples of three varieties grown at four distinct sites. For comparison, tests were also performed with traditional equipment, namely the Mixograph, an extension tester and a Farinograph-type small-scale recording mixer. Uniaxial dough elongation (with an Instron) produced results similar to the conventional extension tester, except that results were provided in fundamental units (Pascals), the critical value recorded being the elongational stress at maximum strain. Stress relaxation measurements were performed following a small initial shear strain. With this method, it was possible to distinguish between the viscosity and the elastic components of dough visco-elasticity. In all the tests the extra dough-strength properties were evident for the variety (Guardian) that had the 5 + 10 glutenin subunits, in contrast to the other two with the 2 + 12 combination of subunits

Deriving the mass of particles from Extended Theories of Gravity in LHC era

We derive a geometrical approach to produce the mass of particles that could be suitably tested at LHC. Starting from a 5D unification scheme, we show that all the known interactions could be suitably deduced as an induced symmetry breaking of the non-unitary GL(4)-group of diffeomorphisms. The deformations inducing such a breaking act as vector bosons that, depending on the gravitational mass states, can assume the role of interaction bosons like gluons, electroweak bosons or photon. The further gravitational degrees of freedom, emerging from the reduction mechanism in 4D, eliminate the hierarchy problem since generate a cut-off comparable with electroweak one at TeV scales. In this "economic" scheme, gravity should induce the other interactions in a non-perturbative way.Comment: 30 pages, 1 figur

Chirality and Symmetry Breaking in a discrete internal Space

In previous papers the permutation group S_4 has been suggested as an ordering scheme for elementary particles, and the appearance of this finite symmetry group was taken as indication for the existence of a discrete inner symmetry space underlying elementary particle interactions. Here it is pointed out that a more suitable choice than the tetrahedral group S_4 is the pyritohedral group A_4 x Z_2 because its vibrational spectrum exhibits exactly the mass multiplet structure of the 3 fermion generations. Furthermore it is noted that the same structure can also be obtained from a primordial symmetry breaking S_4 --> A_4. Since A_4 is a chiral group, while S_4 is achiral, an argument can be given why the chirality of the inner pyritohedral symmetry leads to parity violation of the weak interactions.Comment: 42 pages, 3 table

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.Metabolic health: pathophysiological trajectories and therap

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society