Symmetry Breaking for Matter Coupled to Linearized Supergravity From the Perspective of the Current Supermultiplet

We consider a generic supersymmetric matter theory coupled to linearized supergravity, and analyze scenarios for spontaneous symmetry breaking in terms of vacuum expectation values of components of the current supermultiplet. When the vacuum expectation of the energy momentum tensor is zero, but the scalar current or pseudoscalar current gets an expectation, evaluation of the gravitino self energy using the supersymmetry current algebra shows that there is an induced gravitino mass term. The structure of this term generalizes the supergravity action with cosmological constant to theories with CP violation. When the vacuum expectation of the energy momentum tensor is nonzero, supersymmetry is broken; requiring cancellation of the cosmological constant gives the corresponding generalized gravitino mass formula.Comment: 11 page

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial

Michael A Patane¹, Amy Cohen¹, Stephen From¹, Gail Torkildsen², Donna Welch³, George W Ousler III³¹Eyegate Pharmaceuticals, Inc, Waltham, MA, USA; ²Andover Eye Associates, Andover, MA, USA; ³Ora, Inc, Andover, MA, USAPurpose: To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients.Methods: The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.5 mA-min at 2.5 mA (DP 7.5, n = 41); 10.5 mA-min at 3.5 mA (DP 10.5, n = 37); or 10.5 mA-min at 3.5 mA (placebo, n = 25). Three CAE visits and 4 follow-up visits occurred over 3 weeks. Patients meeting enrollment criteria received iontophoresis in both eyes after the second CAE exposure (visit 3) and before the third CAE exposure (visit 5). Primary efficacy endpoints were corneal staining and ocular discomfort. Secondary endpoints included tear film break-up time, ocular protection index (OPI), and symptomatology.Results: The DP 7.5 and DP 10.5 treatment groups showed statistically significant improvements in signs and symptoms of dry eye at various time points; however, the primary endpoints were not achieved. The DP 7.5 treatment group exhibited statistically significant improvements in corneal staining (when comparing the differences between study entry and exit, 3 weeks, P = 0.039), OPI (immediately following the second treatment, P = 0.048) and ocular discomfort at follow-up visits (a week after the first treatment, P = 0.032; 24 hours after the second treatment, P = 0.0032). Treatment-emergent adverse events (AEs) were experienced by 87% of patients and were consistent across all treatment groups. Most AEs were mild and no severe AEs were observed.Conclusion: Ocular iontophoresis of EGP-437 demonstrated statistically and clinically significant improvements in signs and symptoms of dry eye syndrome within a CAE model.Keywords: iontophoresis, dry eye, Controlled Adverse Environment (CAE), ocular protection index (OPI

Generalized stochastic Schroedinger equations for state vector collapse

A number of authors have proposed stochastic versions of the Schr\"odinger equation, either as effective evolution equations for open quantum systems or as alternative theories with an intrinsic collapse mechanism. We discuss here two directions for generalization of these equations. First, we study a general class of norm preserving stochastic evolution equations, and show that even after making several specializations, there is an infinity of possible stochastic Schr\"odinger equations for which state vector collapse is provable. Second, we explore the problem of formulating a relativistic stochastic Schr\"odinger equation, using a manifestly covariant equation for a quantum field system based on the interaction picture of Tomonaga and Schwinger. The stochastic noise term in this equation can couple to any local scalar density that commutes with the interaction energy density, and leads to collapse onto spatially localized eigenstates. However, as found in a similar model by Pearle, the equation predicts an infinite rate of energy nonconservation proportional to $\delta^3(\vec 0)$, arising from the local double commutator in the drift term.Comment: 24 pages Plain TeX. Minor changes, some new references. To appear in Journal of Physics

A design for cancer case–control studies using only incident cases: experience with the GEM study of melanoma

BACKGROUND: The population-based case-control study is not suited to the evaluation of rare genetic (or environmental) factors. The use of a novel case-control design in which cases have second primaries and controls are cancer survivors has been proposed for this purpose. METHODS: We report results from an international study of melanoma that involved population-based ascertainment of incident cases of second or subsequent primary melanoma as the 'case' group and incident cases of first primary melanoma as the 'control' group. We evaluate the validity of the study design by comparing the results obtained for phenotypic factors that have been shown consistently to be associated with melanoma in previous conventional studies with the results from a conventional case-control study conducted in Connecticut and from literature reviews. RESULTS: All but one of the known risk factors for melanoma were shown to be significantly associated with melanoma in our study, though the individual odds ratios appear to be somewhat attenuated relative to the magnitudes typically observed in the literature. CONCLUSIONS: Patients with a second or subsequent primary cancer of a single type represent a potentially valuable and under-utilized resource for the study of cancer aetiology

CDKN2A Germline Mutations in Individuals with Cutaneous Malignant Melanoma

Cyclin-dependent kinase inhibitor type 2A (CDKN2A) has been identified as a major melanoma susceptibility gene based on the presence of germline mutations in high-risk melanoma families. In this study, we sought to identify and characterize the spectrum of CDKN2A mutations affecting p16 inhibitor of cyclin-dependent kinase type 4 (INK4a) in individuals with melanoma using a population-based study design. DNA samples from 1189 individuals with incident multiple primary melanoma (MPM) and 2424 with incident single primary melanoma unselected for family history of melanoma were available for screening of CDKN2A (p16INK4a) mutations. Variants were classified for functional impact based on intragenic position, existing functional data, sequence, and structural analysis. The impact of individual mutations and functional groupings was assessed by comparing frequencies in cases of MPM versus cases with a single first primary melanoma, and by comparing the reported incidence rates in first-degree relatives. Our results show that mutations occur infrequently in these high-risk groups, and that they occur mainly in exons 1alpha and 2. Rare coding variants with putative functional impact are observed to increase substantially the risk of melanoma. With the exception of the variant in position -34 of CDKN2A of known functional consequence, the remaining rare variants in the non-coding region have no apparent impact on risk

Torture and the UK’s “war on asylum”: medical power and the culture of disbelief

When the now ‘iconic’ images of shackled, humiliated and dehumanised detainees in the Abu Ghraib prison complex in Iraq were broadcast globally, in the mid-2000s, the relationship between medical power and torture in the “war on terror” was also thrust sharply into focus. Graphic images of coalition troops photographing and posing in front of hooded, naked prisoners forced into a “human pyramid”, and of people made to wear animal collars, indicated a regime in which degradation had a defining role. The photograph of a soldier gloating over the corpse of a man who had died as a result of torture was just one picture of a network of interrogation camps in which detention by coalition forces could be fatal. Yet if there were any expectations that the presence of medical personnel may have checked this violence, these were shattered by the fact that clinicians – in some cases at least – were integral to its practice. «It is now beyond doubt that Armed Forces physicians, psychologists, and medics were active and passive partners in the systematic neglect and abuse of war on terror prisoners», wrote Steven Miles in 2009 (Miles 2009, X). And as he continued, this involved providing interrogators «with medical information to use in setting the nature and degree of physical and psychological abuse during interrogations». It involved monitoring «interrogations to devise ways to break prisoners down or to keep them alive». It involved pathologists holding back death certificates and autopsy reports in order to minimise the number of fatalities or cover up torture-related deaths as deaths by natural causes (Ibid). Procedures including «cramped confinement, dietary manipulation, sleep deprivation, and waterboarding» were among the practices that were «at times (…) legally sanctioned due to medical supervision» in the context of the “war on terror”, according to Hoffman (2011, 1535). He continued to suggest that doctors are not just important to «modern torture methods», they are «irreplaceable». In this context, the “war on terror” is no aberration. As the revolutionary psychoanalyst and philosopher Frantz Fanon documented in 1959, for example, certain medical practitioners had an integral role in the military occupation of Algeria, and «There are, for instance, psychiatrists … known to numerous prisoners», he suggested, «who have given electric shock treatments to the accused and have questioned them during the waking phase, which is characterized by a certain confusion, a relaxation of resistance, a disappearance of the person's defences.» (Fanon 1959/1965, 138). Indeed, in his analysis of the Algerian revolution, he discussed how resistance to and struggles over the meanings of medical power were integral to the revolution itself. However, while the role of medical power in the practice of torture has been subjected to sustained critique in the context of the “war on terror”, what follows examines the relationship between medical power and torture in the context of what has been depicted – metaphorically – as another (although to some extents related) “war”: the “war” on asylum. According to the UNHCR (2017, 3), between 5 and 35 per cent of those asylum seekers who have been granted refugee status have survived torture. And focusing on the UK as a case study, this chapter examines the institutional and legal structures prohibiting torture and inhuman and degrading treatment, particularly as they apply to those subject to immigration control in this context. But further, it also examines the ideological and political conditions within which claims by those seeking asylum that they have been subjected to torture prior to arrival can be (and have been) ignored, downplayed and denied. It examines how medical expertise has frequently been undermined in the asylum process when this expertise is utilised to add weight to asylum seekers’ claims to have experienced torture. It examines how there have been attempts to narrow the definition of torture in ways which exclude people from the protections to which torture survivors are entitled. But it also explores the ways in which segments of the medical profession have been complicit in riding roughshod over existing safeguards to prevent further harm to those who have experienced torture, thus potentially compounding its effects. In particular, it examines claims that in certain contexts clinicians have administered dangerous “care” in order to ensure the removal of people from the UK, despite them claiming that they – or their family members – face serious harm and persecution on arrival as a result of this. In a historical discussion of medical involvement in torture, Giovanni Maio (2001, 1609) has noted that from its earliest incarnations one of the features of torture has been its use as an «oppressive instrument used in the preservation of power». Furthermore, whilst methods of torture have certainly «developed», and continue to do so, he argues, this «function» of torture is «especially relevant today». This chapter argues that the (mis)treatment of those in the UK who say they have been tortured, preserves and is bound up with a particular manifestation of state power: the aims, rationale and dictates of immigration control. Its claims are perhaps much more mundane than the forms of direct medical complicity in torture alluded to above. But they are nonetheless important. For it is argued that the acts of omission and commission documented in this chapter expose the tensions between the rights of certain “categories” of migrants to be afforded adequate clinical care on the one hand, and the goals and aims of immigration control itself on the other. This poses profound questions about the functions of clinical care and the ethical duties, responsibilities and obligations of clinicians, it is suggested. But as this chapter also crucially explores, this is a form of power that many within the medical profession have historically challenged, and continue to do so

Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study

Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics

Clinicopathologic Features of Incident and Subsequent Tumors in Patients with Multiple Primary Cutaneous Melanomas

0.6–12.7% of patients with primary cutaneous melanoma will develop additional melanomas. Pathologic features of tumors in patients with multiple primary cutaneous melanomas have not been well described. In this large international multi-center case-control study, we compared the clinicopathologic features of a subsequent melanoma with the preceding (usually the first) melanoma in patients with multiple primary cutaneous melanomas, and with those of melanomas in patients with single primary cutaneous melanomas