Effects of human recombinant growth hormone on exercise capacity, cardiac structure, and cardiac function in patients with adult-onset growth hormone deficiency

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group

Multiple transcriptome mining coupled with tissue specific molecular cloning and mass spectrometry provide insights into agatoxin-like peptide conservation in decapod crustaceans

Over the past decade, in silico genome and transcriptome mining has led to the identification of many new crustacean peptide families, including the agatoxin-like peptides (ALPs), a group named for their structural similarity to agatoxin, a spider venom component. Here, analysis of publicly accessible transcriptomes was used to expand our understanding of crustacean ALPs. Specifically, transcriptome mining was used to investigate the phylogenetic/structural conservation, tissue localization, and putative functions of ALPs in decapod species. Transcripts encoding putative ALP precursors were identified from one or more members of the Penaeoidea (penaeid shrimp), Sergestoidea (sergestid shrimps), Caridea (caridean shrimp), Astacidea (clawed lobsters and freshwater crayfish), Achelata (spiny/slipper lobsters), and Brachyura (true crabs), suggesting a broad, and perhaps ubiquitous, conservation of ALPs in decapods. Comparison of the predicted mature structures of decapod ALPs revealed high levels of amino acid conservation, including eight identically conserved cysteine residues that presumably allow for the formation of four identically positioned disulfide bridges. All decapod ALPs are predicted to have amidated carboxyl-terminals. Two isoforms of ALP appear to be present in most decapod species, one 44 amino acids long and the other 42 amino acids in length, both likely generated by alternative splicing of a single gene. In carideans, a gene or terminal exon duplication appears to have occurred, with alternative splicing producing four ALPs, two 44 and two 42 amino acid isoforms. The identification of ALP precursor-encoding transcripts in nervous system-specific transcriptomes (e.g., Homarus americanus brain, eyestalk ganglia, and cardiac ganglion assemblies, finding confirmed using RT-PCR) suggests that members of this peptide family may serve as locally-released and/or hormonally-delivered neuromodulators in decapods. Their detection in testis- and hepatopancreas-specific transcriptomes suggests that members of the ALP family may also play roles in male reproduction and innate immunity/detoxification

State/Operator Correspondence in Higher-Spin dS/CFT

A recently conjectured microscopic realization of the dS$_4$/CFT$_3$ correspondence relating Vasiliev's higher-spin gravity on dS$_4$ to a Euclidean $Sp(N)$ CFT$_3$ is used to illuminate some previously inaccessible aspects of the dS/CFT dictionary. In particular it is argued that states of the boundary CFT$_3$ on $S^2$ are holographically dual to bulk states on geodesically complete, spacelike $R^3$ slices which terminate on an $S^2$ at future infinity. The dictionary is described in detail for the case of free scalar excitations. The ground states of the free or critical $Sp(N)$ model are dual to dS-invariant plane-wave type vacua, while the bulk Euclidean vacuum is dual to a certain mixed state in the CFT$_3$. CFT$_3$ states created by operator insertions are found to be dual to (anti) quasinormal modes in the bulk. A norm is defined on the $R^3$ bulk Hilbert space and shown for the scalar case to be equivalent to both the Zamolodchikov and pseudounitary C-norm of the $Sp(N)$ CFT$_3$.Comment: 24 page

AMGSEFLamide, a member of a broadly conserved peptide family, modulates multiple neural networks in Homarus americanus

Recent genomic/transcriptomic studies have identified a novel peptide family whose members share the carboxyl terminal sequence –GSEFLamide. However, the presence/identity of the predicted isoforms of this peptide group have yet to be confirmed biochemically, and no physiological function has yet been ascribed to any member of this peptide family. To determine the extent to which GSEFLamides are conserved within the Arthropoda, we searched publicly accessible databases for genomic/transcriptomic evidence of their presence. GSEFLamides appear to be highly conserved within the Arthropoda, with the possible exception of the Insecta, in which sequence evidence was limited to the more basal orders. One crustacean in which GSEFLamides have been predicted using transcriptomics is the lobster, Homarus americanus. Expression of the previously published transcriptome-derived sequences was confirmed by reverse transcription (RT)-PCR of brain and eyestalk ganglia cDNAs; mass spectral analyses confirmed the presence of all six of the predicted GSEFLamide isoforms – IGSEFLamide, MGSEFLamide, AMGSEFLamide, VMGSEFLamide, ALGSEFLamide and AVGSEFLamide – in H. americanus brain extracts. AMGSEFLamide, of which there are multiple copies in the cloned transcripts, was the most abundant isoform detected in the brain. Because the GSEFLamides are present in the lobster nervous system, we hypothesized that they might function as neuromodulators, as is common for neuropeptides. We thus asked whether AMGSEFLamide modulates the rhythmic outputs of the cardiac ganglion and the stomatogastric ganglion. Physiological recordings showed that AMGSEFLamide potently modulates the motor patterns produced by both ganglia, suggesting that the GSEFLamides may serve as important and conserved modulators of rhythmic motor activity in arthropods

Qualitative Analysis of Isotropic Curvature String Cosmologies

A complete qualitative study of the dynamics of string cosmologies is presented for the class of isotopic curvature universes. These models are of Bianchi types I, V and IX and reduce to the general class of Friedmann-Robertson-Walker universes in the limit of vanishing shear isotropy. A non-trivial two-form potential and cosmological constant terms are included in the system. In general, the two-form potential and spatial curvature terms are only dynamically important at intermediate stages of the evolution. In many of the models, the cosmological constant is important asymptotically and anisotropy becomes dynamically negligible. There also exist bouncing cosmologies.Comment: Accepted to Classical and Quantum Gravity, 40 pages, 12 figures (uses "graphicx" package for figures

Dynamic hip screw fixation of subtrochanteric femoral fractures.

INTRODUCTION: A subtrochanteric proximal femur fracture occurs in the 5 cm of bone immediately distal to the lesser trochanter. UK national guidelines advise that adults with subtrochanteric fractures should be treated with an intramedullary nail (IMN). This study aims to compare peri-operative outcome measures of patients with subtrochanteric fractures treated with either an IMN or a dynamic hip screw (DHS) construct. MATERIALS AND METHODS: We retrospectively reviewed subtrochanteric fractures presenting at our institution over 4.5 years (October 2014-May 2019), classifying them into two treatment groups; IMN and DHS. These groups were compared on outcome measures including surgical time, blood loss, radiation dose area product (DAP), length of stay, re-operation rate and mortality. RESULTS: During the time period studied, 86 patients presented with a subtrochanteric fracture of the femur; with 74 patients (86%) receiving an IMN and 12 (14%) receiving a DHS. The comparative outcome measures reaching statistical significance were blood loss and radiation DAP. The DHS group showed a significantly lower mean blood loss of 776 ml compared to 1029 ml in the IMN group. Also, the DHS group showed a significantly lower mean DAP of 150.30 mGy cm2 compared to 288.86 mGy cm2 in the IMN group. CONCLUSION: Although UK national guidelines recommend treating all subtrochanteric fractures with an IMN; the outcome measures assessed in our study did not show use of an IMN to be superior to a DHS. The DHS group showed a lower estimated blood loss and a reduced DAP. This, along with the reduced financial cost associated with a DHS, may support the use of DHS over IMN for certain subtrochanteric fractures of the femur. There may not be a single favourable implant for the treatment of subtrochanteric fractures as a whole; instead different subtypes of fracture may be amenable to a number of fixation devices. Choice of implant should be determined locally and based on existing and future clinical and health economic research

WARNING: Physics Envy May Be Hazardous To Your Wealth!

The quantitative aspirations of economists and financial analysts have for many years been based on the belief that it should be possible to build models of economic systems - and financial markets in particular - that are as predictive as those in physics. While this perspective has led to a number of important breakthroughs in economics, "physics envy" has also created a false sense of mathematical precision in some cases. We speculate on the origins of physics envy, and then describe an alternate perspective of economic behavior based on a new taxonomy of uncertainty. We illustrate the relevance of this taxonomy with two concrete examples: the classical harmonic oscillator with some new twists that make physics look more like economics, and a quantitative equity market-neutral strategy. We conclude by offering a new interpretation of tail events, proposing an "uncertainty checklist" with which our taxonomy can be implemented, and considering the role that quants played in the current financial crisis.Comment: v3 adds 2 reference