Management of the Acute Scrotum in a District General Hospital: 10-Year Experience

The acutely painful scrotum is a common urologic emergency. The primary objective of management is to avoid testicular loss. This requires a high index of clinical suspicion and prompt surgical intervention. In our series conducted between January 1996 and December 2005, 119 patients (age range: 4–62 years) underwent emergency operative exploration for acute scrotal pain. The most common finding was torted cyst of Morgagni (63/119, 52.9%), followed by testicular torsion (41/119, 34.4%). The majority of testicular torsions occurred in the pubertal group (22/41, 53.6%). Only one patient in this group had an unsalvageable testis necessitating orchidectomy, a testicular loss rate in torsion of 2.4%. There were no postoperative wound infections or scrotal haematomas. Testicular salvage depends critically on early surgical intervention, so the delay incurred in diagnostic imaging may extend the period of ischaemia. Furthermore, all radiological investigations have a certain false-negative rate. We advocate immediate surgical exploration of the acute scrotum. We report a low orchidectomy rate (2.4%) in testicular torsion

Transversely Driven Charge Density Waves and Striped Phases of High-Tc_c Superconductors: The Current Effect Transistor

We show that a normal (single particle) current density $J_x$ {\em transverse} to the ordering wavevector $2k_F{\bf\hat{z}}$ of a charge density wave (CDW) has dramatic effects both above and {\em below} the CDW depinning transition. It exponentially (in $J_x$) enhances CDW correlations, and exponentially suppresses the longitudinal depinning field. The intermediate longitudinal I-V relation also changes, acquiring a {\em linear} regime. We propose a novel ``current effect transistor'' whose CDW channel is turned on by a transverse current. Our results also have important implications for the recently proposed ``striped phase'' of the high-T$_c$ superconductors.Comment: change of title and minor corrections, 4 RevTeX pgs, to appear in Phys. Rev. Lett., 81, 3711 (1998

Five-Year Follow Up of a Low Glycaemic Index Dietary Randomised Controlled Trial in Pregnancy—No Long-Term Maternal Effects of a Dietary Intervention

Objective: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. Design: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. Setting: Dublin, Ireland (2007–2016). Population: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. Methods: Fasting glucose was measured at 13 and 28 weeks’ gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. Outcome: Maternal diet, HbA1c, and weight retention at 5 years post-intervention. Results: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36–3.04) and parity ≥3 (B 1.04, 95% CI 0.09–1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B −0.06, 95% CI −0.11 to −0.02), gestational weight gain (B 0.19, 95% CI 0.00–0.38), and GI (B 0.26, 95% CI 0.06–0.46) at 5 years. Conclusions: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. Tweetable abstract: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Scaling of magnetic fluctuations near a quantum phase transition

We use inelastic neutron scattering to measure the magnetic fluctuations in a single crystal of the heavy fermion alloy CeCu_5.9Au_0.1 close to the antiferromagnetic quantum critical point. The energy and temperature-dependent spectra obey (E/T) scaling at Q near (1,0,0). The neutron data and earlier bulk susceptibility are consistent with the form 1/X ~ f(Q)+(-iE+bT)^a, with an anomalous exponent a=0.8. We confirm the earlier observation of quasi-low dimensionality and show how both the magnetic fluctuations and the thermodynamics can be understood in terms of a quantum Lifshitz point.Comment: Latex file with two postscript figure

Turnip mosaic potyvirus probably first spread to Eurasian brassica crops from wild orchids about 1000 years ago

Turnip mosaic potyvirus (TuMV) is probably the most widespread and damaging virus that infects cultivated brassicas worldwide. Previous work has indicated that the virus originated in western Eurasia, with all of its closest relatives being viruses of monocotyledonous plants. Here we report that we have identified a sister lineage of TuMV-like potyviruses (TuMV-OM) from European orchids. The isolates of TuMV-OM form a monophyletic sister lineage to the brassica-infecting TuMVs (TuMV-BIs), and are nested within a clade of monocotyledon-infecting viruses. Extensive host-range tests showed that all of the TuMV-OMs are biologically similar to, but distinct from, TuMV-BIs and do not readily infect brassicas. We conclude that it is more likely that TuMV evolved from a TuMV-OM-like ancestor than the reverse. We did Bayesian coalescent analyses using a combination of novel and published sequence data from four TuMV genes [helper component-proteinase protein (HC-Pro), protein 3(P3), nuclear inclusion b protein (NIb), and coat protein (CP)]. Three genes (HC-Pro, P3, and NIb), but not the CP gene, gave results indicating that the TuMV-BI viruses diverged from TuMV-OMs around 1000 years ago. Only 150 years later, the four lineages of the present global population of TuMV-BIs diverged from one another. These dates are congruent with historical records of the spread of agriculture in Western Europe. From about 1200 years ago, there was a warming of the climate, and agriculture and the human population of the region greatly increased. Farming replaced woodlands, fostering viruses and aphid vectors that could invade the crops, which included several brassica cultivars and weeds. Later, starting 500 years ago, inter-continental maritime trade probably spread the TuMV-BIs to the remainder of the world

Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

PURPOSE In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF–wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy

Metformin is a metabolic modulator and radiosensitiser in rectal cancer

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer