Persistent threats to validity in single‐group interrupted time series analysis with a cross over design

Rationale, aims and objectivesThe basic single‐group interrupted time series analysis (ITSA) design has been shown to be susceptible to the most common threat to validity—history—the possibility that some other event caused the observed effect in the time series. A single‐group ITSA with a crossover design (in which the intervention is introduced and withdrawn 1 or more times) should be more robust. In this paper, we describe and empirically assess the susceptibility of this design to bias from history.MethodTime series data from 2 natural experiments (the effect of multiple repeals and reinstatements of Louisiana’s motorcycle helmet law on motorcycle fatalities and the association between the implementation and withdrawal of Gorbachev’s antialcohol campaign with Russia’s mortality crisis) are used to illustrate that history remains a threat to ITSA validity, even in a crossover design.ResultsBoth empirical examples reveal that the single‐group ITSA with a crossover design may be biased because of history. In the case of motorcycle fatalities, helmet laws appeared effective in reducing mortality (while repealing the law increased mortality), but when a control group was added, it was shown that this trend was similar in both groups. In the case of Gorbachev’s antialcohol campaign, only when contrasting the results against those of a control group was the withdrawal of the campaign found to be the more likely culprit in explaining the Russian mortality crisis than the collapse of the Soviet Union.ConclusionsEven with a robust crossover design, single‐group ITSA models remain susceptible to bias from history. Therefore, a comparable control group design should be included, whenever possible.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136538/1/jep12668.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136538/2/jep12668_am.pd

The influence of HLA matching on cytomegalovirus hepatitis and chronic rejection after liver transplantation

Previous findings in liver transplantation patients have raised the concept that HLA plays a dualistic role. HLA matching will reduce rejection but may augment MHC restricted cellular immune mechanisms of liver allograft injury. To evaluate this concept, we studied CMV hepatitis in 399 FK506-treated liver transplant patients, including 355 cases for which complete HLA-A, B, DR, DQ typing information was available. CMV hepatitis developed in 25 patients, and 17 of them (or 68%) showed a one or two HLA-DR antigen match with the donor. In contrast, HLA-DR matches were found in only 35% of 330 patients without CMV hepatitis (P=0.005). No significant associations were seen for HLA-A, HLA-B, and HLA-DQ antigens. In pretransplant CMV-seronegative patients with seropositive grafts (n=39), the frequency of CMV hepatitis was 44% for HLA-DR-matched livers but 14% for HLA-DR-un-matched livers. In seropositive recipients (n=187), these frequencies were 12% and 2% for HLA-DR-matched and unmatched liver grafts. Chronic rejection developed in 29 patients (or 8%) during a follow-up between 10 and 24 months after transplantation. Its incidence was higher in the CMV hepatitis group (24% vs. 6%) (P=0.007). Although no associations were found between HLA matching and the incidence of chronic rejection, there was an earlier onset of chronic rejection of HLA-DR-matched livers irrespective of CMV hepatitis. These findings suggest that an HLA-DR match between donor and recipient increases the incidence of CMV hepatitis in both primary and secondary CMV infections. Although HLA compatibility leads to less acute cellular rejection, it is suggested that DR matching may accelerate chronic rejection of liver transplants, perhaps through HLA-DR-restricted immunological mechanisms toward viral antigens, including CMV. © 1993 by Williams and Wilkins

Unwanted effects: Is there a negative side of meditation? A multicentre survey

Objectives Despite the long-term use and evidence-based efficacy of meditation and mindfulness-based interventions, there is still a lack of data about the possible unwanted effects (UEs) of these practices. The aim of this study was to evaluate the occurrence of UEs among meditation practitioners, considering moderating factors such as the type, frequency, and lifetime duration of the meditation practices. Methods An online survey was developed and disseminated through several websites, such as Spanish-, English- and Portuguese-language scientific research portals related to mindfulness and meditation. After excluding people who did not answer the survey correctly or completely and those who had less than two months of meditation experience, a total of 342 people participated in the study. However, only 87 reported information about UEs. Results The majority of the practitioners were women from Spain who were married and had a University education level. Practices were more frequently informal, performed on a daily basis, and followed by focused attention (FA). Among the participants, 25.4% reported UEs, showing that severity varies considerably. The information requested indicated that most of the UEs were transitory and did not lead to discontinuing meditation practice or the need for medical assistance. They were more frequently reported in relation to individual practice, during focused attention meditation, and when practising for more than 20 minutes and alone. The practice of body awareness was associated with UEs to a lesser extent, whereas focused attention was associated more with UEs. Conclusions This is the first large-scale, multi-cultural study on the UEs of meditation. Despite its limitations, this study suggests that UEs are prevalent and transitory and should be further studied. We recommend the use of standardized questionnaires to assess the UEs of meditation practices

MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy

Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering

Polarized deep--inelastic scattering data on longitudinally polarized hydrogen and deuterium targets have been used to determine double spin asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for the production of positive and negative pions from hydrogen were obtained in a re--analysis of previously published data. Inclusive and semi--inclusive asymmetries for the production of negative and positive pions and kaons were measured on a polarized deuterium target. The separate helicity densities for the up and down quarks and the anti--up, anti--down, and strange sea quarks were computed from these asymmetries in a ``leading order'' QCD analysis. The polarization of the up--quark is positive and that of the down--quark is negative. All extracted sea quark polarizations are consistent with zero, and the light quark sea helicity densities are flavor symmetric within the experimental uncertainties. First and second moments of the extracted quark helicity densities in the measured range are consistent with fits of inclusive data

Imaging the spine in arthritis—a pictorial review

Spinal involvement is frequent in rheumatoid arthritis (RA) and seronegative spondyloarthritides (SpA), and its diagnosis is important. Thus, MRI and CT are increasingly used, although radiography is the recommended initial examination. The purpose of this review is to present the typical radiographic features of spinal changes in RA and SpA in addition to the advantages of MRI and CT, respectively. RA changes are usually located in the cervical spine and can result in serious joint instability. Subluxation is diagnosed by radiography, but supplementary MRI and/or CT is always indicated to visualise the spinal cord and canal in patients with vertical subluxation, neck pain and/or neurological symptoms. SpA may involve all parts of the spine. Ankylosing spondylitis is the most frequent form of SpA and has rather characteristic radiographic features. In early stages it is characterised by vertebral squaring and condensation of vertebral corners, in later stages by slim ossifications between vertebral bodies, vertebral fusion, arthritis/ankylosis of apophyseal joints and ligamentous ossification causing spinal stiffness. The imaging features of the other forms of SpA can vary, but voluminous paravertebral ossifications often occur in psoriatic SpA. MRI can detect signs of active inflammation as well as chronic structural changes; CT is valuable for detecting fracture

Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction

Evidence for a narrow baryon state is found in quasi-real photoproduction on a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1 (syst) MeV. Depending on the background model,the naive statistical significance of the peak is 4--6 standard deviations and its width may be somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s)) pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed in the pK^+ invariant mass distribution. The absence of such a signal indicates that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure

A review of trisomy X (47,XXX)

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment

P300 amplitude is insensitive to working memory load in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects.</p> <p>Methods</p> <p>We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory.</p> <p>Results</p> <p>In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs.</p> <p>Conclusions</p> <p>SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients.</p

A comparative study on long-term evoked auditory and visual potential responses between Schizophrenic patients and normal subjects

<p>Abstract</p> <p>Background</p> <p>The electrical signals measuring method is recommended to examine the relationship between neuronal activities and measure with the event related potentials (ERPs) during an auditory and a visual oddball paradigm between schizophrenic patients and normal subjects. The aim of this study is to discriminate the activation changes of different stimulations evoked by auditory and visual ERPs between schizophrenic patients and normal subjects.</p> <p>Methods</p> <p>Forty-three schizophrenic patients were selected as experimental group patients, and 40 healthy subjects with no medical history of any kind of psychiatric diseases, neurological diseases, or drug abuse, were recruited as a control group. Auditory and visual ERPs were studied with an oddball paradigm. All the data were analyzed by SPSS statistical software version 10.0.</p> <p>Results</p> <p>In the comparative study of auditory and visual ERPs between the schizophrenic and healthy patients, P300 amplitude at Fz, Cz, and Pz and N100, N200, and P200 latencies at Fz, Cz, and Pz were shown significantly different. The cognitive processing reflected by the auditory and the visual P300 latency to rare target stimuli was probably an indicator of the cognitive function in schizophrenic patients.</p> <p>Conclusions</p> <p>This study shows the methodology of application of auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have different response properties. Our study indicates that there may be slowness of automatic cognitive processing and controlled cognitive processing of visual ERPs compared to auditory ERPs in schizophrenic patients. The activation changes of visual evoked potentials are more regionally specific than auditory evoked potentials.</p