Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements

Motor Agency: A New and Highly Sensitive Measure to Reveal Agency Disturbances in Early Psychosis

Background: Early diagnosis of young adults at risk of schizophrenia is essential for preventive approaches of the illness. Nevertheless, classic screening instruments are difficult to use because of the non-specific nature of the signs at this preonset phase of illness. The objective of the present contribution was to propose an innovating test that can probe the more specific symptom of psychosis, i.e., the sense of agency, which is defined as being the immediate experience of oneself as the cause of an action. More specifically, we tested whether motor agency is abnormal in early psychosis. Methods: Thirty-two young symptomatic patients and their age-matched controls participated in the study. 15 of these patients were at ultra high-risk for developing psychosis (UHR), and 17 patients were suffering from first-episode psychosis (FEP). Patients ’ neurocognitive capacities were assessed through the use of seven neuropsychological tests. A motor agency task was also introduced to obtain an objective indicator of the degree of sense of agency, by contrasting force levels applied during other and self-produced collisions between a hand-held objet and a pendulum. Results: As reported in the literature for adult controls, healthy adolescents used more efficient force levels in self than in other-imposed collisions. For both UHR and FEP patients, abnormally high levels of grip force were used for self-produced collisions, leading to an absence of difference between self and other. The normalized results revealed that motor agency differentiated patients from controls with a higher level of sensitivity than the more classic neuropsychological test battery

Slepian functions and their use in signal estimation and spectral analysis

It is a well-known fact that mathematical functions that are timelimited (or spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the finite precision of measurement and computation unavoidably bandlimits our observation and modeling scientific data, and we often only have access to, or are only interested in, a study area that is temporally or spatially bounded. In the geosciences we may be interested in spectrally modeling a time series defined only on a certain interval, or we may want to characterize a specific geographical area observed using an effectively bandlimited measurement device. It is clear that analyzing and representing scientific data of this kind will be facilitated if a basis of functions can be found that are "spatiospectrally" concentrated, i.e. "localized" in both domains at the same time. Here, we give a theoretical overview of one particular approach to this "concentration" problem, as originally proposed for time series by Slepian and coworkers, in the 1960s. We show how this framework leads to practical algorithms and statistically performant methods for the analysis of signals and their power spectra in one and two dimensions, and on the surface of a sphere.Comment: Submitted to the Handbook of Geomathematics, edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verla

Supersymmetric Monojets at the Large Hadron Collider

Supersymmetric monojets may be produced at the Large Hadron Collider by the process qg -> squark neutralino_1 -> q neutralino_1 neutralino_1, leading to a jet recoiling against missing transverse momentum. We discuss the feasibility and utility of the supersymmetric monojet signal. In particular, we examine the possible precision with which one can ascertain the neutralino_1-squark-quark coupling via the rate for monojet events. Such a coupling contains information on the composition of the neutralino_1 and helps bound dark matter direct detection cross-sections and the dark matter relic density of the neutralino_1. It also provides a check of the supersymmetric relation between gauge couplings and gaugino-quark-squark couplings.Comment: 46 pages, 10 figures. The appendix has been rewritten to correct an error that appears in all previous versions of the appendix. This error has no effect on the results in the main body of the pape

Scalar and vector Slepian functions, spherical signal estimation and spectral analysis

It is a well-known fact that mathematical functions that are timelimited (or spacelimited) cannot be simultaneously bandlimited (in frequency). Yet the finite precision of measurement and computation unavoidably bandlimits our observation and modeling scientific data, and we often only have access to, or are only interested in, a study area that is temporally or spatially bounded. In the geosciences we may be interested in spectrally modeling a time series defined only on a certain interval, or we may want to characterize a specific geographical area observed using an effectively bandlimited measurement device. It is clear that analyzing and representing scientific data of this kind will be facilitated if a basis of functions can be found that are "spatiospectrally" concentrated, i.e. "localized" in both domains at the same time. Here, we give a theoretical overview of one particular approach to this "concentration" problem, as originally proposed for time series by Slepian and coworkers, in the 1960s. We show how this framework leads to practical algorithms and statistically performant methods for the analysis of signals and their power spectra in one and two dimensions, and, particularly for applications in the geosciences, for scalar and vectorial signals defined on the surface of a unit sphere.Comment: Submitted to the 2nd Edition of the Handbook of Geomathematics, edited by Willi Freeden, Zuhair M. Nashed and Thomas Sonar, and to be published by Springer Verlag. This is a slightly modified but expanded version of the paper arxiv:0909.5368 that appeared in the 1st Edition of the Handbook, when it was called: Slepian functions and their use in signal estimation and spectral analysi

FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections

Protocol for implementation of family health history collection and decision support into primary care using a computerized family health history system

<p>Abstract</p> <p>Background</p> <p>The CDC's Family History Public Health Initiative encourages adoption and increase awareness of family health history. To meet these goals and develop a personalized medicine implementation science research agenda, the Genomedical Connection is using an implementation research (T3 research) framework to develop and integrate a self-administered computerized family history system with built-in decision support into 2 primary care clinics in North Carolina.</p> <p>Methods/Design</p> <p>The family health history system collects a three generation family history on 48 conditions and provides decision support (pedigree and tabular family history, provider recommendation report and patient summary report) for 4 pilot conditions: breast cancer, ovarian cancer, colon cancer, and thrombosis. All adult English-speaking, non-adopted, patients scheduled for well-visits are invited to complete the family health system prior to their appointment. Decision support documents are entered into the medical record and available to provider's prior to the appointment. In order to optimize integration, components were piloted by stakeholders prior to and during implementation. Primary outcomes are change in appropriate testing for hereditary thrombophilia and screening for breast cancer, colon cancer, and ovarian cancer one year after study enrollment. Secondary outcomes include implementation measures related to the benefits and burdens of the family health system and its impact on clinic workflow, patients' risk perception, and intention to change health related behaviors. Outcomes are assessed through chart review, patient surveys at baseline and follow-up, and provider surveys. Clinical validity of the decision support is calculated by comparing its recommendations to those made by a genetic counselor reviewing the same pedigree; and clinical utility is demonstrated through reclassification rates and changes in appropriate screening (the primary outcome).</p> <p>Discussion</p> <p>This study integrates a computerized family health history system within the context of a routine well-visit appointment to overcome many of the existing barriers to collection and use of family history information by primary care providers. Results of the implementation process, its acceptability to patients and providers, modifications necessary to optimize the system, and impact on clinical care can serve to guide future implementation projects for both family history and other tools of personalized medicine, such as health risk assessments.</p

Utility of In Vivo Transcription Profiling for Identifying Pseudomonas aeruginosa Genes Needed for Gastrointestinal Colonization and Dissemination

Microarray analysis of Pseudomonas aeruginosa mRNA transcripts expressed in vivo during animal infection has not been previously used to investigate potential virulence factors needed in this setting. We compared mRNA expression in bacterial cells recovered from the gastrointestinal (GI) tracts of P. aeruginosa-colonized mice to that of P. aeruginosa in the drinking water used to colonize the mice. Genes associated with biofilm formation and type III secretion (T3SS) had markedly increased expression in the GI tract. A non-redundant transposon library in P. aeruginosa strain PA14 was used to test mutants in genes identified as having increased transcription during in vivo colonization. All of the Tn-library mutants in biofilm-associated genes had an attenuated ability to form biofilms in vitro, but there were no significant differences in GI colonization and dissemination between these mutants and WT P. aeruginosa PA14. To evaluate T3SS factors, we tested GI colonization and neutropenia-induced dissemination of both deletional (PAO1 and PAK) and insertional (PA14) mutants in four genes in the P. aeruginosa T3SS, exoS or exoU, exoT, and popB. There were no significant differences in GI colonization among these mutant strains and their WT counterparts, whereas rates of survival following dissemination were significantly decreased in mice infected by the T3SS mutant strains. However, there was a variable, strain-dependent effect on overall survival between parental and T3SS mutants. Thus, increased transcription of genes during in vivo murine GI colonization is not predictive of an essential role for the gene product in either colonization or overall survival following induction of neutropenia

Surviving streptococcal toxic shock syndrome: a case report

Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans) streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored