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Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999–2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08–3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.
This study used a single case experimental design to investigate the use of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) among a sample of individuals with depression and anxiety who also presented with borderline personality disorder (BPD). Eight women received individual treatment with the UP over the course of 14–16 treatment sessions, and were assessed for anxiety and depression severity on a weekly basis over a 2–6 week baseline period and throughout treatment. Three of the eight participants demonstrated reliable pre- to post-treatment clinical improvements on depression and stress scales, and one participant demonstrated a reliable reduction on an anxiety scale. Two participants demonstrated a reliable improvement in overall anxiety. The results indicate that the UP applied to individuals diagnosed with primary BPD may lead to clinical improvement in depression, stress and anxiety for some individuals. However, the majority of individuals with BPD in our sample did not show strong improvement, and this suggests the need for additional sessions of UP or an intervention that focuses on the symptoms of BPD specifically for some women.
Key learning aims
(1)To describe the applicability of the Unified Protocol in the treatment of individuals with borderline personality and co-occurring anxiety or depression.
(2)To understand the value of utilizing a transdiagnostic approach as an alternative to diagnosis-specific approaches to treatment.
(3)To identify the four core modules of the Unified Protocol and describe the general format for individual treatment.
We present possible conceptual designs of a laser system for driving table-top free-electron lasers based on terahertz acceleration. After discussing the achievable performances of laser amplifiers with Yb:YAG at cryogenic and room temperature and Yb:YLF at cryogenic temperature, we present amplification modules with available results and concepts of amplifier chains based on these laser media. Their performances are discussed in light of the specifications for the tasks within the table-top light source. Technical and engineering challenges, such as cooling, control, synchronization and diagnostics, are outlined. Three concepts for the laser layout feeding the accelerator are eventually derived and presented.
Several infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1, Helicobacter pylori, Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N = 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (β = −0·1204 (standard error (s.e.) 0·06), P = 0·044) and (β = −0·1057 (s.e. = 0·05), P = 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples.
Maternal smoking has consistently been associated with multiple adverse childhood outcomes including externalizing disorders. In contrast the association between maternal smoking during pregnancy (MSDP) and internalizing (anxiety and depressive) disorders in offspring has received less investigation.
We conducted a nationwide cohort study including 957635 individuals born in Denmark between 1991 and 2007. Data on MSDP and diagnoses of depression or anxiety disorders were derived from national registers and patients were followed up from the age of 5 years to the end of 2012. Hazard rate ratios (HRRs) were estimated using stratified Cox regression models. Sibling data were used to disentangle individual- and familial-level effects of MSDP and to control for unmeasured familial confounding.
At the population level, offspring exposed to MSDP were at increased risk for both severe depression [HRR 1.29, 95% confidence interval (CI) 1.22–1.36] and severe anxiety disorders (HRR 1.26, 95% CI 1.20–1.32) even when controlling for maternal and paternal traits. However, there was no association between MSDP and internalizing disorders when controlling for the mother's propensity for MSDP (depression: HRR 1.11, 95% CI 0.94–1.30; anxiety disorders: HRR 0.94, 95% CI 0.80–1.11) or comparing differentially exposed siblings (depression: HRR 1.18, 95% CI 0.75–1.89; anxiety disorders: HRR 0.87, 95% CI 0.55–1.36).
The results suggest that familial background factors account for the association between MSDP and severe internalizing disorders not the specific exposure to MSDP.
Palliative care is an interdisciplinary approach to caring for individuals and families who are suffering with serious illness. Medical and psycho-social-spiritual symptoms and needs are assessed and addressed. Much of palliative care is about working with patients and families to bring their context to light, that is, to understand not only their medical situation but also their wishes, values, cultural background, previous experiences, and quality of life. As palliative care clinicians, we have seen how popular understanding and misunderstanding about what it means to “honor thy mother and father” can influence medical decision making. Whether or not adult children of patients have familiarity with the honor commandment, the biblical text “honor thy father and mother,” or whether they identify with a particular religious tradition, this theme plays a central—and often unaddressed—role as adult children strive to make decisions with and for a seriously ill parent. In this article we examine the commandment to honor one's father and mother by exploring its religious, spiritual, textual, and cultural origins, as well as subsequent Jewish commentary. We also contextualize the honor commandment in the palliative care setting through clinical case studies that illustrate the concerns of adult children who wish to honor their parents but are perplexed or conflicted about what this mandate means in the face of difficult medical and psycho-social-spiritual circumstances.
To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood.
Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972–1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years.
A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80).
A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.
Background: There are no disease modifying agents for the treatment of Alzheimer’s disease (AD). Pathologically, AD is associated with the misfolding of two peptides: beta-amyloid (plaques) and tau (tangles). Methods: Using large-scale computer simulations, we modelled the misfolding of both beta-amyloid and tau, identifying a common conformational motif (CCM; i.e. an abnormal peptide shape), present in both beta-amyloid and tau, that promotes their misfolding. We screened a library of 11.8 million compounds against this in silico model of protein misfolding, identifying three novel molecular classes of putative therapeutics as anti-protein misfolding agents. We synthesized approximately 400 new chemical entity drug-like molecules in each of these three classes (i.e. 1200 potential drug candidates). These were comprehensively screened in a battery of five in vitro protein oligomerization assays. Selected compounds were next evaluated in the APP/PS1 doubly transgenic mouse model of AD. Results: Two new classes of molecules were identified with the ability to block the oligomerization of both beta-amyloid and tau. These compounds are drug-like with good pharmacokinetic properties and are brain-penetrant. They exhibit excellent efficacy in transgenic mouse models. Conclusion: Computer aided drug design has enabled the discovery of novel drug-like molecules able to inhibit both tau and beta-amyloid misfolding.
Precipitation of amorphous silica (SiO2) in geothermal power plants, although a common factor limiting the efficiency of geothermal energy production, is poorly understood and no universally applicable mitigation strategy to prevent or reduce precipitation is available. This is primarily due to the lack of understanding of the precipitation mechanism of amorphous silica in geothermal systems.
In the present study data are presented about microstructures and compositions of precipitates formed on scaling plates inserted at five different locations in the pipelines at the Hellisheiði power station (SW-Iceland). Precipitates on these plates formed over 6 to 8 weeks of immersion in hot (120 or 60ºC), fast-flowing and silica-supersaturated geothermal fluids (~800 ppm of SiO2). Although the composition of the precipitates is fairly homogeneous, with silica being the dominant component and Fe sulfides as a less common phase, the microstructures of the precipitates are highly variable and dependent on the location within the geothermal pipelines. The silica precipitates have grown through aggregation and precipitation of silica particles that precipitated homogeneously in the geothermal fluid. Five main factors were identified that may control the precipitation of silica: (1) temperature, (2) fluid composition, (3) fluid-flow regime, (4) distance along the flow path, and (5) immersion time.
On all scaling plates, a corrosion layer was found underlying the silica precipitates indicating that, once formed, the presence of a silica layer probably protects the steel pipe surface against further corrosion. Yet silica precipitates influence the flow of the geothermal fluids and therefore can limit the efficiency of geothermal power stations.
The jet of BL Lac displays transverse patterns that propagate downstream superluminally. We suggest that they are transverse Alfvén waves propagating on the longitudinal component of a helical magnetic field. The speed of the wave adds relativistically to the speed of the beam, and the apparent speed of the pattern is greater than the beam speed. Models for the jet and the MHD waves give values for the Lorentz factor of the beam of 3–4.4 and pitch angle of the helical magnetic field of 43° - 65°. These are consistent with other estimates, if the beam and pattern speeds are allowed to differ.
The purpose of the present study is to identify child and adult correlates that differentiate (a) individuals with persistent alcohol dependence from individuals with developmentally limited alcohol dependence and (b) individuals with adult-onset alcohol dependence from individuals who never diagnose. There are 1,037 members of the Dunedin Longitudinal Study, which is a birth cohort followed prospectively from birth until age 32. Past-year DSM-IV alcohol dependence diagnoses are ascertained with structured diagnostic interviews at ages 18, 21, 26, and 32. Individuals are classified as developmentally limited, persistent, or adult-onset subtypes based on their time-ordered pattern of diagnoses. The persistent subtype generally exhibits the worst scores on all correlates, including family psychiatric history, adolescent and adult externalizing and internalizing problems, adolescent and adult substance use, adult quality of life, and coping strategies. The prospective predictors that distinguished them from the developmentally limited subtype involved family liability, adolescent negative affectivity, daily alcohol use, and frequent marijuana use. Furthermore, young people who develop the persistent subtype of alcohol dependence are distinguished from the developmentally limited subtype by an inability to reduce drinking and by continued use despite problems by age 18. The adult-onset group members are virtually indistinguishable from ordinary cohort members as children or adolescents; however, in adulthood, adult-onset cases are distinguished by problems with depression, substance use, stress, and strategies for coping with stress. Information about age of onset and developmental course is fundamental for identifying subtypes of alcohol dependence. Subtype-specific etiologies point to targeted prevention and intervention efforts based on the characteristics of each subtype.
A clinically compatible fluorescence lifetime imaging microscopy (FLIM) system was developed. The system was applied to intraoperative in vivo imaging of head and neck squamous cell carcinoma (HNSCC). The endoscopic FLIM prototype integrates a gated (down to 0.2 ns) intensifier imaging system and a fiber-bundle endoscope (0.5-mm-diameter, 10,000 fibers with a gradient index lens objective 0.5 NA, 4-mm field of view), which provides intraoperative access to the surgical field. Tissue autofluorescence was induced by a pulsed laser (337 nm, 700 ps pulse width) and collected in the 460 ± 25 nm spectral band. FLIM experiments were conducted at 26 anatomic sites in ten patients during head and neck cancer surgery. HNSCC exhibited a weaker florescence intensity (~50% less) when compared with healthy tissue and a shorter average lifetime (τHNSCC = 1.21 ± 0.04 ns) than the surrounding normal tissue (τN = 1.49 ± 0.06 ns). This work demonstrates the potential of FLIM for label-free head and neck tumor demarcation during intraoperative surgical procedures.
Precision optical astrometry of quasars and active galaxies can provide important insight into the spatial distribution and variability of emission in compact nuclei. SIM — the Space Interferometry Mission — will be the first optical interferometer capable of precision astrometry on quasars. Although it is not expected to resolve the emission, it will be very sensitive to astrometric shifts, for objects as faint as R magnitude 20. In its wide-angle mode, SIM will yield 4 microarcsecond absolute positions, and proper motions to about 2 microarcsecond/yr. A variety of AGN phenomena are expected to be visible to SIM on these scales, including time and spectral dependence in position offsets between accretion disk and jet emission. SIM should be able to answer the following questions. Does the most compact optical emission from an AGN come from an accretion disk or from a relativistic jet? Do the relative positions of the radio core and optical photocentre of quasars used for the reference frame tie change on the timescales of their photometric variability? Do the cores of galaxies harbour binary supermassive black holes remaining from galaxy mergers? In this paper we briefly describe the operation of SIM and the quasar measurements it will make. We estimate the size of the astrometric signatures which may be expected, and we discuss prospects for using astrometry as a fundamental tool for understanding quasar nuclei.
Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have cast doubt on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age.
Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence.
Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and post-traumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38.
Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly.