Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays

The OPERA experiment, designed to perform the first observation of νμ→ντ oscillations in appearance mode through the detection of the τ leptons produced in ντ charged current interactions, has collected data from 2008 to 2012. In the present paper, the procedure developed to detect τ particle decays, occurring over distances of the order of 1 mm from the neutrino interaction point, is described in detail. The results of its application to the search for charmed hadrons are then presented as a validation of the methods for ντ appearance detection.

Is hysterectomy nowadays an obsolete procedure?

After the general morbidity reduction at the beginning of the century and the routine use of prophylactic antibiotics, a hysterectomy was generously, sometimes to generously indicated in the middle of the 20th century. This might be one of the major reasons why the procedure got a bad reputation. Furthermore, in the last decade, several new treatments for benign uterine pathologies have been developed which can be proposed to the patients instead of performing a hysterectomy. Therefore, the question might be asked, if nowadays there are still some indications for a hysterectomy or if the procedure is obsolete.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.

[Pilot Project: Improved Lung Deposition via a New Nasal Inhalation Procedure].

INTRODUCTION Inhaled drugs can only be effective if they reach the middle and small airways. This study introduces a system that combines a trans-nasal application of aerosols with noninvasive pressure support ventilation. METHODS In a pilot study, 7 COPD patients with GOLD stages II and III inhaled a radiolabeled marker dissolved in water via a trans-nasal route. The mean aerosol particle size was 5.5 µm. Each patient took part in two inhalation sessions that included two application methods and were at least 70 hours apart. During the first session ("passive method"), the patient inhaled the aerosol through an open tube system. The second session ("active method") included pressure support ventilation during the inhalation process. A gamma camera and planar scintigraphy was used to determine the distribution of aerosol particles in the patient's body and lung. RESULTS The pressure supported inhalation ("active method") results in an increased aerosol lung deposition compared to the passive method. Above all, we could demonstrate deposition in the lung periphery with relatively large aerosol particles (5.5 µm). DISCUSSION The results prove that the combination of trans-nasal inhalation with noninvasive pressure support ventilation leads to significantly increased particle deposition in the lung.

Increased spread and replication efficiency of Listeria monocytogenes in organotypic brain-slices is related to multilocus variable number of tandem repeat analysis (MLVA) complex.

BACKGROUND Listeria (L.) monocytogenes causes fatal infections in many species including ruminants and humans. In ruminants, rhombencephalitis is the most prevalent form of listeriosis. Using multilocus variable number tandem repeat analysis (MLVA) we recently showed that L. monocytogenes isolates from ruminant rhombencephalitis cases are distributed over three genetic complexes (designated A, B and C). However, the majority of rhombencephalitis strains and virtually all those isolated from cattle cluster in MLVA complex A, indicating that strains of this complex may have increased neurotropism and neurovirulence. The aim of this study was to investigate whether ruminant rhombencephalitis strains have an increased ability to propagate in the bovine hippocampal brain-slice model and can be discriminated from strains of other sources. For this study, forty-seven strains were selected and assayed on brain-slice cultures, a bovine macrophage cell line (BoMac) and a human colorectal adenocarcinoma cell line (Caco-2). They were isolated from ruminant rhombencephalitis cases (n = 21) and other sources including the environment, food, human neurolisteriosis cases and ruminant/human non-encephalitic infection cases (n = 26). RESULTS All but one L. monocytogenes strain replicated in brain slices, irrespectively of the source of the isolate or MLVA complex. The replication of strains from MLVA complex A was increased in hippocampal brain-slice cultures compared to complex C. Immunofluorescence revealed that microglia are the main target cells for L. monocytogenes and that strains from MLVA complex A caused larger infection foci than strains from MLVA complex C. Additionally, they caused larger plaques in BoMac cells, but not CaCo-2 cells. CONCLUSIONS Our brain slice model data shows that all L. monocytogenes strains should be considered potentially neurovirulent. Secondly, encephalitis strains cannot be conclusively discriminated from non-encephalitis strains with the bovine organotypic brain slice model. The data indicates that MLVA complex A strains are particularly adept at establishing encephalitis possibly by virtue of their higher resistance to antibacterial defense mechanisms in microglia cells, the main target of L. monocytogenes.

An analysis of two methods for the classification of stage of readiness to obtain repeat mammography screening

Background and purpose: Breast cancer continues to be a health problem for women, representing 28 percent of all female cancers and remaining one of the leading causes of death for women. Breast cancer incidence rates become substantial before the age of 50. After menopause, breast cancer incidence rates continue to increase with age creating a long-lasting source of concern (Harris et al., 1992). Mammography, a technique for the detection of breast tumors in their nonpalpable stage when they are most curable, has taken on considerable importance as a public health measure. The lifetime risk of breast cancer is approximately 1 in 9 and occurs over many decades. Recommendations are that screening be periodic in order to detect cancer at early stages. These recommendations, largely, are not followed. Not only are most women not getting regular mammograms, but this circumstance is particularly the case among older women where regular mammography has been proven to reduce mortality by approximately 30 percent. The purpose of this project was to increase our understanding of factors that are associated with stage of readiness to obtain subsequent mammograms. A secondary purpose of this research was to suggest further conceptual considerations toward the extension of the Transtheoretical Model (TTM) of behavior change to repeat screening mammography. ^ Methods. A sample (n = 1,222) of women 50 years and older in a large multi-specialty clinic in Houston, Texas was surveyed by mail questionnaire regarding their previous screening experience and stage of readiness to obtain repeat screening. A computerized database, maintained on all women who undergo mammography at the clinic, was used to identify women who are eligible for the project. The major statistical technique employed to select the significant variables and to examine the man and interaction effects of independent variables on dependent variables was polychotomous stepwise, logistic regression. A prediction model for each stage of readiness definition was estimated. The expected probabilities for stage of readiness were calculated to assess the magnitude and direction of significant predictors. ^ Results. Analysis showed that both ways of defining stage of readiness for obtaining a screening mammogram were associated with specific constructs, including decisional balance and processes of the change. ^ Conclusions. The results of the present study demonstrate that the TTM appears to translate to repeat mammography screening. Findings in the current study also support finding of previous studies that suggest that stage of readiness is associated with respondent decisional balance and the processes of change. ^

Deterrence, Incapacitation, and Repeat Offenders

This paper develops an economic model of criminal enforcement that combines the goals of deterrence and incapacitation. Potential offenders commit an initial criminal act if the present value of net private gains is positive. A fraction of these offenders become habitual and commit further crimes immediately upon release from their initial prison term (if any). The optimal punishment scheme in this setting generally involves a finite prison term for first-time offenders (based on the goal of deterrence), and an infinite (life) sentence for repeat offenders (based on the goal of incapacitation).

Test, Edit, Repeat: Steps to Improve Your Web Site.

Presents ways to improve library Web sites. Description of the Hampshire College library Web site and how it is an integral part of the college's reference service; Usability analysis of Web sites; How to apply what librarians learn from usability analysis; Importance of testing; How to measure success. INSETS: Test Questions; Usability Guidelines.

A Simple Theory of Increasing Penalties for Repeat Offenders

A feature of many penal codes is that punishments are more severe for repeat offenders, yet economic models have had a hard time providing a theoretical justification for this practice. This paper offers an explanation based on the wage penalty suffered by individuals convicted of crime. While this penalty probably deters some first-timers from committing crimes, it actually hampers deterrence of repeat offenders because of their diminished employments opportunities. We show that in this setting, an escalating penalty scheme is optimal and time consistent.

A Bootstrap-Regression Procedure to Capture Unit Specific Effects in Data Envelopment Analysis

The Data Envelopment Analysis (DEA) efficiency score obtained for an individual firm is a point estimate without any confidence interval around it. In recent years, researchers have resorted to bootstrapping in order to generate empirical distributions of efficiency scores. This procedure assumes that all firms have the same probability of getting an efficiency score from any specified interval within the [0,1] range. We propose a bootstrap procedure that empirically generates the conditional distribution of efficiency for each individual firm given systematic factors that influence its efficiency. Instead of resampling directly from the pooled DEA scores, we first regress these scores on a set of explanatory variables not included at the DEA stage and bootstrap the residuals from this regression. These pseudo-efficiency scores incorporate the systematic effects of unit-specific factors along with the contribution of the randomly drawn residual. Data from the U.S. airline industry are utilized in an empirical application.

DNA incisions stimulate genetic instability of triplet repeat sequences related to human hereditary neurological diseases

The molecular mechanisms responsible for the expansion and deletion of trinucleotide repeat sequences (TRS) are the focus of our studies. Several hereditary neurological diseases including Huntington's disease, myotonic dystrophy, and fragile X syndrome are associated with the instability of TRS. Using the well defined and controllable model system of Escherichia coli, the influences of three types of DNA incisions on genetic instability of CTG•CAG repeats were studied: DNA double-strand breaks (DSB), single-strand nicks, and single-strand gaps. The DNA incisions were generated in pUC19 derivatives by in vitro cleavage with restriction endonucleases. The cleaved DNA was then transformed into E. coli parental and mutant strains. Double-strand breaks induced deletions throughout the TRS region in an orientation dependent manner relative to the origin of replication. The extent of instability was enhanced by the repeat length and sequence (CTG•CAG vs. CGG•CCG). Mutations in recA and recBC increased deletions, mutations in recF stabilized the TRS, whereas mutations in ruvA had no effect. DSB were repaired by intramolecular recombination, versus an intermolecular gene conversion or crossover mechanism. 30 nt gaps formed a distinct 30 nt deletion product, whereas single strand nicks and gaps of 15 nts did not induce expansions or deletions. Formation of this deletion product required the CTG•CAG repeats to be present in the single-stranded region and was stimulated by E. coli DNA ligase, but was not dependent upon the RecFOR pathway. Models are presented to explain the DSB induced instabilities and formation of the 30 nucleotide deletion product. In addition to the in vitro creation of DSBs, several attempts to generate this incision in vivo with the use of EcoR I restriction modification systems were conducted. ^

The in vivo and in vitro formation of sticky DNA and the GAA.TTC trinucleotide repeat associated with Friedreich's ataxia

Friedreich's ataxia is caused by the expansion of the GAA•TTC trinucleotide repeat sequence located in intron 1 of the frataxin gene. The long GAA•TTC repeats are known to form several non-B DNA structures including hairpins, triplexes, parallel DNA and sticky DNA. Therefore it is believed that alternative DNA structures play a role in the loss of mRNA transcript and functional frataxin protein in FRDA patients. We wanted to further elucidate the characteristics for formation and stability of sticky DNA by evaluating the structure in a plasmid based system in vitro and in vivo in Escherichia coli. The negative supercoil density of plasmids harboring different lengths of GAA•TTC repeats, as well as either one or two repeat tracts were studied in E. coli to determine if plasmids containing two long tracts (≥60 repeats) in a direct repeat orientation would have a different topological effect in vivo compared to plasmids that harbored only one GAA•TTC tract or two tracts of < 60 repeats. The experiments revealed that, in fact, sticky DNA forming plasmids had a lower average negative supercoil density (-σ) compared to all other control plasmids used that had the potential to form other non-B DNA structures such as triplexes or Z-DNA. Also, the requirements for in vitro dissociation and reconstitution of the DNA•DNA associated region of sticky DNA were evaluated. Results conclude that the two repeat tracts associate in the presence of negative supercoiling and MgCl 2 or MnCl2 in a time and concentration-dependent manner. Interaction of the repeat sequences was not observed in the absence of negative supercoiling and/or MgCl2 or in the presence of other monovalent or divalent cations, indicating that supercoiling and quite specific cations are needed for the association of sticky DNA. These are the first experiments studying a more specific role of supercoiling and cation influence on this DNA conformation. To support our model of the topological effects of sticky DNA in plasmids, changes in sticky DNA band migration was measured with reference to the linear DNA after treatment with increasing concentrations of ethidium bromide (EtBr). The presence of independent negative supercoil domains was confirmed by this method and found to be segregated by the DNA-DNA associated region. Sequence-specific polyamide molecules were used to test the effect of binding of the ligands to the GAA•TTC repeats on the inhibition of sticky DNA. The destabilization of the sticky DNA conformation in vitro through this binding of the polyamides demonstrated the first conceptual therapeutic approach for the treatment of FRDA at the DNA molecular level. ^ Thus, examining the properties of sticky DNA formed by these long repeat tracts is important in the elucidation of the possible role of sticky DNA in Friedreich's ataxia. ^

A standard operation procedure and a pilot water testing for herbicides in northwest Harris County, Texas

Herbicides are used to control the growth of weeds along highways, power lines, and many other urban locations. Exposure to herbicides has been linked to adverse health outcomes. This study was initiated to pretest for the presence of herbicides in multiple water sources near intersections in a corridor in the Northwest Harris County (specifically in the Highway 6/FM 1960, North Freeway 45, US 290 and S 99 corridor). Roadside water and tap water samples were collected and analyzed for herbicides using the established Environmental Protection Agency (EPA) Method 515.4: "Determination of Chlorinated Acids in Drinking Water by Liquid-Liquid Micro-extraction, Derivatization, and Fast Gas Chromatography with Electron Capture Detection." A standard operating procedure (adapted from the US EPA Method 515.4) was developed for subsequent, larger studies of environmental fate of herbicides and non-occupational exposure risks. Preliminary testing of 16 water samples was performed to pretest the existence of trace herbicides; all concentrations that were greater than the minimum reporting limits of each analyte are reported with a 99 percent confidence. This study failed to find concentrations above the limits of detection of the method in any of the samples collected on June 15, 2008. However, this does not indicate that the waters around the NW Harris County are free of herbicides and metabolites. A larger and repeated sampling in the region would be necessary to make that claim. ^

Procedure for the identification of population characteristics for targeting intervention services on the basis of outcome-goal priorities: Case management services for the chronic mentally ill

Although the processes involved in rational patient targeting may be obvious for certain services, for others, both the appropriate sub-populations to receive services and the procedures to be used for their identification may be unclear. This project was designed to address several research questions which arise in the attempt to deliver appropriate services to specific populations. The related difficulties are particularly evident for those interventions about which findings regarding effectiveness are conflicting. When an intervention clearly is not beneficial (or is dangerous) to a large, diverse population, consensus regarding withholding the intervention from dissemination can easily be reached. When findings are ambiguous, however, conclusions may be impossible.^ When characteristics of patients likely to benefit from an intervention are not obvious, and when the intervention is not significantly invasive or dangerous, the strategy proposed herein may be used to identify specific characteristics of sub-populations which may benefit from the intervention. The identification of these populations may be used both in further informing decisions regarding distribution of the intervention and for purposes of planning implementation of the intervention by identifying specific target populations for service delivery.^ This project explores a method for identifying such sub-populations through the use of related datasets generated from clinical trials conducted to test the effectiveness of an intervention. The method is specified in detail and tested using the example intervention of case management for outpatient treatment of populations with chronic mental illness. These analyses were applied in order to identify any characteristics which distinguish specific sub-populations who are more likely to benefit from case management service, despite conflicting findings regarding its effectiveness for the aggregate population, as reported in the body of related research. However, in addition to a limited set of characteristics associated with benefit, the findings generated, a larger set of characteristics of patients likely to experience greater improvement without intervention. ^