Malignant melanoma: a study of 283 cases with comments and suggestions on treatment

The first and basic result of this study is to show that radiation is by no means useless in malignant melanoma. Even as a palliative it appears to increase survival and certainly is a safer and more sure way of relieving local symptoms than any chemotherapeutic agent yet tried extensively. The fact that the established disease can respond in the great majority of cases has been obscured by the relative minority of spectacular failures.In view of this and the disappointing results of surgery at least in certain situations» e.g. trunk and foot lesions it is perhaps worthwhile trying it in an attempt to improve the results in the elderly, unfit and more advanced case in whom the prognosis evEn with - or perhaps especially with - radical surgery is poor.It would appear that any case with obviously involved nodes is beyond help by surgery alone. DICKSON (1958) has shown the improvement which post-operative radiation can achieve in early cases. It is postulated that in the advanoed case intensive radiation may prolong the patient's life and preserve the functional integrity of his extremities with a better chance of so doing if surgery is not embarked upon

An exercise-only intervention in obese fathers restores glucose and insulin regulation in conjunction with the rescue of pancreatic islet cell morphology and microRNA expression in male offspring

Published: 9 February 2017Paternal obesity programs metabolic syndrome in offspring. Low-impact exercise in obese males improves the metabolic health of female offspring, however whether this occurred in male offspring remained unknown. C57BL/6NHsd (Harlan) mice were fed a control diet (CD; 6% fat, n = 7) or a high-fat diet (HFD; 21% fat, n = 16) for 18 weeks. After 9 weeks, HFD-fed mice either remained sedentary (HH, n = 8) or undertook low-moderate exercise (HE, n = 8) for another 9 weeks. Male offspring were assessed for glucose/insulin tolerance, body composition, plasma lipids, pancreatic islet cell morphology and microRNA expression. Founder HH induced glucose intolerance, insulin insensitivity, and hyperlipidaemia in male offspring (p < 0.05). Metabolic health was fully restored in male offspring by founder exercise to control levels. Founder HH reduced pancreatic β-cell area and islet cell size in male offspring, and altered the expression of 13 pancreatic microRNAs (p < 0.05). Founder HE led to partial restoration of pancreatic islet cell morphology and the expression of two pancreatic microRNAs (let7d-5p, 194-5p) in male offspring. Founder HE reduced male offspring adiposity, increased muscle mass, reduced plasma free fatty acids (FFAs), and further altered pancreatic microRNAs (35 vs. HH; 32 vs. CD) (p < 0.05). Low-impact exercise in obese fathers prior to conception, without dietary change, may be a viable intervention strategy to reduce the illeffects of obesity-induced paternal programming in male offspring.Nicole O. McPherson, Michelle Lane, Lauren Sandeman, Julie A. Owens and Tod Fullsto

Sperm microRNA content is altered in a mouse model of male obesity, but the same suite of microRNAs are not altered in offspring's sperm

The prevalence of obesity is increasing worldwide and has tripled in men of reproductive age since the 1970s. Concerningly, obesity is not only comorbid with other chronic diseases, but there is mounting evidence that it increases the non-communicable disease load in their children (eg mortality, obesity, autism). Animal studies have demonstrated that paternal obesity increases the risk of metabolic (eg glucose metabolism defects, obesity) and reproductive disorders in offspring. Epigenetic changes within sperm are clear mechanistic candidates that are associated with both changes to the father’s environment and offspring phenotype. Specifically there is emerging evidence that a father’s sperm microRNA content both responds to paternal environmental cues and alters the gene expression profile and subsequent development of the early embryo. We used a mouse model of high fat diet (HFD) induced obesity to investigate whether male obesity could modulate sperm microRNA content. We also investigated whether this alteration to a father’s sperm microRNA content lead to a similar change in the sperm of male offspring. Our investigations were initially guided by a Taqman PCR array, which indicated the differential abundance of 28 sperm borne microRNAs in HFD mice. qPCR confirmation in a much larger cohort of founder males demonstrated that 13 of these microRNAs were differentially abundant (11 up-regulated; 2 down-regulated) due to HFD feeding. Despite metabolic and reproductive phenotypes also being observed in grand-offspring fathered via the male offspring lineage, there was no evidence that any of the 13 microRNAs were also dysregulated in male offspring sperm. This was presumably due to the variation seen within both groups of offspring and suggests other mechanisms might act between offspring and grand-offspring. Thus 13 sperm borne microRNAs are modulated by a father’s HFD and the presumed transfer of this altered microRNA payload to the embryo at fertilisation potentially acts to alter the embryonic molecular makeup post-fertilisation, altering its growth trajectory, ultimately affecting adult offspring phenotype and may contribute to paternal programming.Tod Fullston, E. Maria C. Ohlsson-Teague, Cristin G. Print, Lauren Y. Sandeman, Michelle Lan

The Normal State Resistivity of Grain Boundaries in YBa2Cu3O7-delta

Using an optimized bridge geometry we have been able to make accurate measurements of the properties of YBa2Cu3O7-delta grain boundaries above Tc. The results show a strong dependence of the change of resistance with temperature on grain boundary angle. Analysis of our results in the context of band-bending allows us to estimate the height of the potential barrier present at the grain boundary interface.Comment: 11 pages, 3 figure

MARVEL Analysis of the Measured High-resolution Rovibronic Spectra of 48 Ti 16 O

Accurate, experimental rovibronic energy levels, with associated labels and uncertainties, are reported for 11 low-lying electronic states of the diatomic ${}^{48}{\mathrm{Ti}}^{16}{\rm{O}}$ molecule, determined using the Marvel (Measured Active Rotational-Vibrational Energy Levels) algorithm. All levels are based on lines corresponding to critically reviewed and validated high-resolution experimental spectra taken from 24 literature sources. The transition data are in the 2–22,160 cm−1 region. Out of the 49,679 measured transitions, 43,885 are triplet–triplet, 5710 are singlet–singlet, and 84 are triplet–singlet transitions. A careful analysis of the resulting experimental spectroscopic network (SN) allows 48,590 transitions to be validated. The transitions determine 93 vibrational band origins of ${}^{48}{\mathrm{Ti}}^{16}{\rm{O}}$, including 71 triplet and 22 singlet ones. There are 276 (73) triplet–triplet (singlet–singlet) band-heads derived from Marvel experimental energies, 123(38) of which have never been assigned in low- or high-resolution experiments. The highest J value, where J stands for the total angular momentum, for which an energy level is validated is 163. The number of experimentally derived triplet and singlet ${}^{48}{\mathrm{Ti}}^{16}{\rm{O}}$ rovibrational energy levels is 8682 and 1882, respectively. The lists of validated lines and levels for ${}^{48}{\mathrm{Ti}}^{16}{\rm{O}}$ are deposited in the supporting information to this paper

Repeat multiparametric MRI in prostate cancer patients on active surveillance

Introduction This study was conducted to describe the changes in repeat multiparametric MRI (mpMRI) occurring in prostate cancer (PCa) patients during active surveillance (AS), and to study possible associations between mpMRI-related parameters in predicting prostate biopsy (Bx) Gleason score (GS) upgrading > 3+3 and protocol-based treatment change (TC). Materials and methods The study cohort consisted of 76 AS patients with GS 3+3 PCa and at least two consecutive mpMRIs of the prostate performed between 2006-2015. Patients were followed according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and an additional mpMRI. The primary end points were GS upgrading (GU) (> 3+3) in protocol-based Bxs and protocol-based TC. Results Out of 76 patients, 53 (69%) had progression (PIRADS upgrade, size increase or new lesion [s]), while 18 (24%) had radiologically stable disease, and 5 (7%) had regression (PIRADS or size decrease, disappearance of lesion[s]) in repeat mpMRIs during AS. PIRADS scores of 4-5 in the initial mpMRI were associated with GU (p = 0.008) and protocol-based TC (p = 0.009). Tumour progression on repeat mpMRIs was associated with TC (p = 0.045) but not with GU (p = 1.00). PIRADS scores of 4-5 predict GU (sensitivity 0.80 [95% confidence interval (CI); 0.51-0.95, specificity 0.62 [95% CI; 0.52-0.77]) with PPV and NPV values of 0.34 (95% CI; 0.21-0.55) and 0.93 (95% CI; 0.80-0.98), respectively. Conclusion mpMRI is a useful tool not only to select but also to monitor PCa patients on AS.Peer reviewe

Measuring anisotropic scattering in the cuprates

A simple model of anisotropic scattering in a quasi two-dimensional metal is studied. Its simplicity allows an analytic calculation of transport properties using the Boltzmann equation and relaxation time approximation. We argue that the c-axis magnetoresistance provides the key test of this model of transport. We compare this model with experiments on overdoped Tl-2201 and find reasonable agreement using only weak scattering anisotropy. We argue that optimally doped Tl-2201 should show strong angular-dependent magnetoresistance within this model and would provide a robust way of determining the in-plane scattering anisotropy in the cuprates.Comment: 12 pages, 8 figures, typset in REVTeX 4. Version 2; added references and corrected typo

Heat-capacity anomalies at TscT_{sc} and T∗T^{*} in the ferromagnetic superconductor UGe2_2

The heat-capacity and magnetization measurements under high pressure have been carried out in a ferromagnetic superconductor UGe$_2$. Both measurements were done using a same pressure cell in order to obtain both data for one pressure. Contrary to the heat capacity at ambient pressure, an anomaly is found in the heat capacity at the characteristic temperature $T^{*}$ where the magnetization shows an anomalous enhancement under high pressure where the superconductivity appears. This suggests that a thermodynamic phase transition takes place at $T^{*}$ at least under high pressure slightly below $P_{c}^{*}$ where $T^{*}$ becomes zero. The heat-capacity anomaly associated with the superconducting transition is also investigated, where a clear peak of $C/T$ is observed in a narrow pressure region ($\Delta P \sim 0.1$ GPa) around $P_{c}^{*}$ contrary to the previous results of the resistivity measurement. Present results suggest the importance of the thermodynamic critical point $P_{c}^{*}$ for the appearance of the superconductivity.Comment: 4 pages, 4 figures, to appear in Phys. Rev. B, Rapid Communication

Observational Limit on Gravitational Waves from Binary Neutron Stars in the Galaxy

Using optimal matched filtering, we search 25 hours of data from the LIGO 40-meter prototype laser interferometric gravitational-wave detector for gravitational-wave chirps emitted by coalescing binary systems within our Galaxy. This is the first test of this filtering technique on real interferometric data. An upper limit on the rate R of neutron star binary inspirals in our Galaxy is obtained: with 90% confidence, R< 0.5/hour. Similar experiments with LIGO interferometers will provide constraints on the population of tight binary neutron star systems in the Universe.Comment: RevTeX, minor revisions, exactly as published in PRL 83 (1999) p1498, 4 pages, 2 figures include