Economic contraction, alcohol intoxication and suicide: analysis of the National Violent Death Reporting System.

OBJECTIVES: Although there is a large and growing body of evidence concerning the impact of contracting economies on suicide mortality risk, far less is known about the role alcohol consumption plays in the complex relationship between economic conditions and suicide. The aims were to compare the postmortem alcohol intoxication rates among male and female suicide decedents before (2005-2007), during (2008-2009) and after (2010-2011) the economic contraction in the USA. METHODS: Data from the restricted National Violent Death Reporting System (2005-2011) for male and female suicide decedents aged 20 years and older were analysed by Poisson regression analysis to test whether there was significant change in the fractions of suicide decedents who were acutely intoxicated at the time of death (defined as blood alcohol content ≥0.08 g/dL) prior, during and after the downturn. RESULTS: The fraction of all suicide decedents with alcohol intoxication increased by 7% after the onset of the recession from 22.2% in 2005-2007 to 23.9% in 2008-2011. Compared with the years prior to the recession, male suicide decedents showed a 1.09-fold increased risk of alcohol intoxication within the first 2 years of the recession. Surprisingly, there was evidence of a lag effect among female suicide decedents, who had a 1.14-fold (95% CI 1.02 to 1.27) increased risk of intoxication in 2010-2011 compared with 2005-2007. CONCLUSIONS: These findings suggest that acute alcohol intoxication in suicide interacts with economic conditions, becoming more prevalent during contractions.

Mycobacterial diseases and antitumour necrosis factor therapy in USA.

OBJECTIVE: In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown. METHODS: At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000-2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure. RESULTS: Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02). CONCLUSIONS: Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

Resonant photoemission at the iron M-edge of Fe(CO)5.

High resolution electron kinetic energy spectra of iron pentacarbonyl (Fe(CO)5) are studied in the photon energy range of 40-90 eV. The relative yield of photolines associated with the Fe 3d level shows a Fano line shape at photon energies of 61 eV. The increase in signal from the 3d level is indicative of resonant photoemission involving 3p-3d transitions at the M edge of iron. The signature of this resonance is also present in photolines typically attributed to be mostly CO in character. We use the modulation depth of the Fano resonances to reinterpret the photoelectron lines in the literature.

Time-resolved pump-probe experiments at the LCLS.

The first time-resolved x-ray/optical pump-probe experiments at the SLAC Linac Coherent Light Source (LCLS) used a combination of feedback methods and post-analysis binning techniques to synchronize an ultrafast optical laser to the linac-based x-ray laser. Transient molecular nitrogen alignment revival features were resolved in time-dependent x-ray-induced fragmentation spectra. These alignment features were used to find the temporal overlap of the pump and probe pulses. The strong-field dissociation of x-ray generated quasi-bound molecular dications was used to establish the residual timing jitter. This analysis shows that the relative arrival time of the Ti:Sapphire laser and the x-ray pulses had a distribution with a standard deviation of approximately 120 fs. The largest contribution to the jitter noise spectrum was the locking of the laser oscillator to the reference RF of the accelerator, which suggests that simple technical improvements could reduce the jitter to better than 50 fs.

Strongly dispersive transient Bragg grating for high harmonics.

We create a transient Bragg grating in a high-harmonic generation medium using two counterpropagating pulses. The Bragg grating disperses the harmonics in angle and can diffract a large bandwidth with temporal resolution limited only by the source size.

Ultraintense x-ray induced ionization, dissociation, and frustrated absorption in molecular nitrogen.

Sequential multiple photoionization of the prototypical molecule N2 is studied with femtosecond time resolution using the Linac Coherent Light Source (LCLS). A detailed picture of intense x-ray induced ionization and dissociation dynamics is revealed, including a molecular mechanism of frustrated absorption that suppresses the formation of high charge states at short pulse durations. The inverse scaling of the average target charge state with x-ray peak brightness has possible implications for single-pulse imaging applications.

Auger electron angular distribution of double core-hole states in the molecular reference frame.

The Linac Coherent Light Source free electron laser is a source of high brightness x rays, 2×10(11) photons in a ∼5 fs pulse, that can be focused to produce double core vacancies through rapid sequential ionization. This enables double core vacancy Auger electron spectroscopy, an entirely new way to study femtosecond chemical dynamics with Auger electrons that probe the local valence structure of molecules near a specific atomic core. Using 1.1 keV photons for sequential x-ray ionization of impulsively aligned molecular nitrogen, we observed a rich single-site double core vacancy Auger electron spectrum near 413 eV, in good agreement with ab initio calculations, and we measured the corresponding Auger electron angle dependence in the molecular frame.

Calibration of a high harmonic spectrometer by laser induced plasma emission.

We present a method that allows for a convenient switching between high harmonic generation (HHG) and accurate calibration of the vacuum ultraviolet (VUV) spectrometer used to analyze the harmonic spectrum. The accurate calibration of HHG spectra is becoming increasingly important for the determination of electronic structures. The wavelength of the laser harmonics themselves depend on the details of the harmonic geometry and phase matching, making them unsuitable for calibration purposes. In our calibration mode, the target resides directly at the focus of the laser, thereby enhancing plasma emission and suppressing harmonic generation. In HHG mode, the source medium resides in front or after the focus, showing enhanced HHG and no plasma emission lines. We analyze the plasma emission and use it for a direct calibration of our HHG spectra.

Genetic engineering of bacteria from managed and natural habitats.

The genetic modification of bacteria from natural and managed habitats will impact on the management of agricultural and environmental settings. Potential applications include crop production and protection, degradation or sequestration of environmental pollutants, extraction of metals from ores, industrial fermentations, and productions of enzymes, diagnostics, and chemicals. Applications of this technology will ultimately include the release of beneficial agents in the environment. If safely deployed, genetically modified bacteria should be able to provide significant benefits in the management of environmental systems and in the development of new environmental control processes.

Characteristics of adult male and female firearm suicide decedents: findings from the National Violent Death Reporting System.

OBJECTIVE: To examine the risk factors and precipitating circumstances associated with firearm suicide. METHODS: Data from the restricted National Violent Death Reporting System (2003-6) for 25 491 male and female suicide decedents aged 18 and older were analysed by multiple logistic regression to estimate the relative odds of firearm use with 95% CIs. RESULTS: Firearms were often used in male (58.1%) and female (31.2%) suicides. Among male decedents, older age, veteran status, residing in areas with higher rates of firearm availability, raised blood alcohol concentration, acute crisis and relationship problems were all associated with firearm use. Conversely, men with a diagnosis of a mental health problem, a history of suicide attempts or alcohol problems had lower odds of firearm use. Among female decedents, factors with a significant effect on firearm use included: being older, married, white and a veteran; residing in areas with higher rates of firearm availability; having an acute crisis; having experienced the death of a relative or friend; being depressed; and having relationship problems. Of note, women who had a treated DSM-IV-diagnosed problem, previous suicide attempts and physical health problems were less likely to use firearms. CONCLUSIONS: These findings challenge the conventional view that those who are severely depressed and suicidal are prone to highly lethal methods, such as firearms. Rather, firearms users may be reacting to acute situations.

Biodesulfurization.

Microbial sulfur-specific transformations have been identified that selectively desulfurize organic sulfur compounds in fossil fuels. Recent discoveries related to biodesulfurization mechanisms may lead to commercial applications of biodesulfurization through engineering recombinant strains for over-expression of biodesulfurization genes, removal of end product repression, and/or by combining relevant industrial and environmental traits with improvements in bioprocess design.

Insertion signal sequence fused to minimal peptides elicits specific CD8+ T-cell responses and prolongs survival of thymoma-bearing mice.

CD8+ T-lymphocytes (TCD8+) recognize minimal peptides of 8-10 residues which are the products of intracellularly processed proteins and are presented at the cell surface by major histocompatibility complex class I molecules. An important step in this process is the translocation of processed proteins from the cytosol across the endoplasmic reticulum membrane, mediated by transporter associated with antigen-processing proteins or alternatively by endoplasmic reticulum-insertion signal sequences located at the NH2-terminus of the precursor molecules. We report here that the addition of an endoplasmic reticulum-insertion signal sequence at the NH2-terminus of TCD8+ epitopes from chicken ovalbumin (amino acids 257-264) or a naturally occurring tumor antigen expressed by the murine mastocytoma P815 (P1A amino acids 35-43) significantly enhanced the priming of specific TCD8+ in vivo. The signal sequence did not enhance peptide immunogenicity by merely increasing the hydrophobicity of the peptide, since ovalbumin amino acids 257-264 peptide with the signal sequence at its COOH-terminus did not demonstrate enhanced efficacy. The signal sequence did not act as a helper epitope, since TCD8+ responses were not diminished in class II-deficient transgenic mice or in mice depleted of CD4+ T-cells in vivo. Importantly, a single immunization with the fusion peptide significantly prolonged survival of mice challenged with E.G7OVA, a thymoma transfected with the complementary DNA of chicken ovalbumin.

Enrollment duration, service use, and costs of care for severely mentally ill members of a health maintenance organization.

BACKGROUND: The rapid growth of prepaid health care and the increasing enrollment of Medicaid clients in health maintenance organizations (HMOs) raise concerns about the adequacy of services for persons with severe mental illness in capitated health plans. Uncontrolled studies have suggested that enrollment of HMO members with mental illness may be prematurely terminated. METHODS: We identified 250 adult Kaiser Permanente Northwest Region (Portland, Ore) members who were enrolled during 1986 or 1987 and had chart diagnoses of schizophrenia or bipolar disorder. Severely mentally ill subjects were matched by age and sex with control HMO members with and without diabetes mellitus. Records of the HMO and the state mental health agency were reviewed to determine HMO enrollment duration, private and public service utilization, and HMO costs of care during the 4-year follow-up period. RESULTS: The severely mentally ill subjects had 42 months of HMO enrollment during the follow-up period compared with 37 months for the controls without diabetes mellitus and 47 months for the patients with diabetes mellitus (P < .001). When HMO enrollment prior to the study was taken into account, the severely mentally ill subjects and those with diabetes mellitus had similar membership duration. Among the severely mentally ill subjects, community mental health service use was related to longer duration of HMO enrollment (P < .05) but HMO costs of care per member per month were not related to retention. The severely mentally ill subjects were high users of mental health services but their use of general medical care was similar to that of the controls without diabetes mellitus. CONCLUSIONS: This controlled study found no evidence for early termination of HMO members with costly mental illness. Use of community mental health care was associated with longer duration of HMO enrollment.

Tardive dyskinesia in the aged. Duration of treatment relationships.

Although tardive dyskinesia (TD) is recognized to result from neuroleptic drug exposure, data conflict about the importance of the quantity of that exposure in producing TD. The relationship between duration of neuroleptic treatment (one to 301 months) and TD was studied in 57 elderly psychiatric inpatients. Examinations for TD and parkinsonism were quantified on the Abnormal Involuntary Movement Scale (AIMS) and on a parkinsonism severity scale. Prevalence of presumed TD was 49% and of parkinsonism 51%. Prevalence of TD increased with longer treatment, but parkinsonism was independent of treatment duration. Linear multiple regression analysis showed that the AIMS score was correlated positively with treatment duration and negatively with parkinsonism. Logistic multiple regression analysis verified these relationships and was more successful at predicting TD. The length of neuroleptic treatment necessary to produce TD was calculated from the logistic model at 10.8 months (95% confidence interval, zero to 25.6 months). These analyses showed the greatest rise in risk of TD occurred within the first two years of drug therapy.

Cancer recurrences and secondary primary cancers after use of antihistamines or antidepressants.

OBJECTIVES: Reports in the scientific literature have described accelerated tumor growth in association with antidepressant and antihistamine exposure in experimental rodent cancer models. This study was designed to determine whether exposure to prescription antidepressants or antihistamines is associated with tumor growth in humans. METHODS: Two nested case-control studies were conducted with a cohort of 1467 patients with breast cancer, colon cancer, or melanoma diagnosed between 1988 and 1994. Eligible patients included 95 with a cancer recurrence and 78 with a second primary lesion diagnosed during the follow-up period. Five control subjects were matched to each case patient according to cancer site, stage, and follow-up time. Conditional logistic regression was used to compare risk for tumor recurrence or occurrence of a second primary tumor among patients using antidepressants or antihistamines with risk among unexposed patients. RESULTS: For a cohort of patients who were predominantly female (78%), with breast cancer (57%) and with a tumor in situ or with localized disease (79%), the average age was 62 years at cancer diagnosis and average duration of follow-up period was 2.2 years. Use of antidepressants or antihistamines was unrelated to risk for tumor recurrence (odds ratio, 0.97; 95% confidence interval, 0.52 to 1.78) or second primary tumors (odds ratio, 0.94; 95% confidence interval, 0.50 to 1.77). CONCLUSION: Typical use of antidepressant or antihistamine drugs did not increase risk for recurrent or second primary tumors among patients with cancer.

Lithium use and discontinuation in a health maintenance organization.

OBJECTIVE: For decades, lithium has been prescribed to treat bipolar disorder. Its efficacy has been documented by clinical trials and by data from specialized clinics. An issue of considerable interest is the use of lithium in managed care systems. This project examined the use of lithium and its continuity of use by enrollees of a health maintenance organization (HMO). METHOD: In a 6-year longitudinal cohort study, 1,594 lithium users aged 15 years and older who were enrolled in an HMO were followed from 1986-1991. Data were obtained from automated databases and from medical record review of a random 5% subsample of the group (N = 74). RESULTS: Bipolar disorder was the most frequent morbidity treated. Eighty-four percent (N = 62 or 74) received services from a psychiatrist. Annual prevalence of lithium use increased over the 6-year period from 1.4 to 2.3 persons per thousand HMO members. Duration of use varied widely with some long-term but many short-term users. Discontinuation of treatment was associated with evaluated rates of psychiatric hospitalization and use of psychiatric emergency services. Lithium users were much more likely to receive a variety of other psychotropic drugs than nonusers of the same sex and age. CONCLUSIONS: Lithium use in this population was more often sporadic than continuous. Discontinuation of lithium was associated with psychiatric hospitalization. If lithium is to be a cost-effective treatment for bipolar disorder, managed care systems will need to improve adherence to drug treatment regimens.

An empirical study of emergency commitment.

The authors examine the emergency commitment process in one Oregon county and present data that document the impact of a local detention facility. The study reconfirms the dependence of commitment processes on the mental health system in which they occur, illustrates the relative inability of specific laws to determine the actual nature of commitment processes, provides support for the concept of community care for the people involved, and points to the need for additional research to clarify the effects of commitment procedures.

A method for quantifying and comparing civil commitment processes.

The authors present a three-step civil commitment model and formulas for calculating 1) the probability of release from the commitment process and 2) the relative importance of the three steps in determining outcome. Using data from Oregon's civil commitment process, they present five examples that demonstrate how their method might be used to study and monitor civil commitment processes within and between jurisdictions. The major public policy and research implications are discussed.

Cost-effectiveness considerations for managed care systems: treating depression in primary care.

This article addresses the management of depression in primary care from the perspective of a health maintenance organization. The rise of managed care systems is briefly discussed with reference to their impact on choice of treatment strategies. Cost-effectiveness considerations pertinent to a health maintenance organization are reviewed. A simplified protocol for the treatment of depression with paroxetine or imipramine in the primary care sector is presented and used as an example of cost calculations. Given the assumptions used in this cost-effectiveness model, it appears that the costs of treating depression in primary care with paroxetine are approximately equal to those found with the use of imipramine. Higher acquisition costs of paroxetine are balanced by the greater labor costs associated with imipramine.

Comparison of the effects of acute and subacute treatment of phenobarbital in different strains of mice.

A strain specificity has been demonstrated for the effect of subsequent administration of phenobarbital (PB), in which diethylnitrosamine (DENA)-initiated hepatocarcinogenesis was promoted in C3H mice, inhibited in B6C3F1 (C57BL x C3H) and not affected in C57BL mice. A correlation has been established between the ability of barbiturates and hydantoins to promote tumor formation and their ability to induce liver growth, hepatic DNA synthesis and mixed function oxidase activities. Therefore, we examined in these 3 strains of mice and in C3B6F1 (C3H x C57BL) mice the effect of PB administered in their drinking water for 4 days or 28 days. The liver weight to body weight ratio was increased by PB in all types of mice. Microsomal protein concentrations were increased in C57BL mice after 28 days of treatment, in C3H after both 4 days and 28 days and in B6C3F1 after 4 days of treatment. No effect upon microsomal protein content was observed in C3B6F1 mice. DNA content was increased in C3H mice, both in the 4-day and 28-day treatment groups, while the other strains showed either a decrease or no difference from control. DNA synthesis was elevated in all strains of mice after 4 days of treatment with PB, however, after 28 days of treatment there was either a much reduced increase (C57BL and C3B6F1) or no difference (C3H and B6C3F1) from controls. In all 4 types of mice after 4 and 28 days of treatment, PB increased the concentration of cytochrome P-450, the activity of aminopyrine-N-demethylase (AmDm) and 7-ethoxyresorufin-O-deethylase (ErDe) and the oxidation of testosterone (T). The oxidative metabolites of T were similar in the 4 types of mice.