Photocatalytic building surfaces can harness sunlight to reduce urban air pollution. The NOx abatement capacity of TiO2-coated granules used in roofing products was evaluated for commercial product ...development. A laboratory test chamber and ancillary setup were built following conditions prescribed by ISO Standard 22197-1. It was validated by exposing reference P25-coated aluminum plates to a 3 L min−1 air flow enriched in 1 ppm NO under UVA irradiation (360 nm, 11.5 W m−2). We characterized prototype granule-surfaced asphalt shingles and loose granules prepared with different TiO2 loadings and post-treatment formulations. Tests performed at surface temperatures of 25 and 60 °C showed that NOx abatement was more effective at the higher temperature. Preliminary tests explored the use of 1 ppm NO2 and of 1 ppm and 0.3 ppm NO/NO2 mixtures. Specimens were aged in a laboratory accelerated weathering apparatus, and by exposure to the outdoor environment over periods that included dry and rainy seasons. Laboratory aging led to higher NO removal and NO2 formation rates, and the same catalyst activation was observed after field exposure with frequent precipitation. However, exposure during the dry season reduced the performance. This inactivation was mitigated by cleaning the surface of field-exposed specimens. Doubling the TiO2 loading led to a 50–150% increase in NO removal and NOx deposition rates. Application of different post-treatment coatings decreased NO removal rates (21–35%) and NOx deposition rates (26–74%) with respect to untreated granules. The mass balance of nitrogenated species was assessed by extracting granules after UV exposure in a 1 ppm NO-enriched atmosphere.
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•Photocatalytic de-NOx performance of granules was assessed in the laboratory.•Tests performed at 60 °C showed higher NO removal efficiency than at 25 °C.•Exposed samples were activated by rain and deactivated in the dry season.•Efficacy increased with TiO2 loading, decreased with surface post-treatment.•Most of the nitrate formed as byproduct was extracted from granule surfaces.
Iproniazid and imipramine, the prototypes of monoamine oxidase inhibitor (MAOI) and monoamine (re)uptake inhibitor (MAUI) antidepressants, were introduced in 1957. The relationship between ...iproniazid's antidepressant effect and its MAO inhibiting property was tenuous. Because of the potential drug-drug interactions and the need for dietary restrictions, the use of MAOIs became restricted to atypical depression. The confounding of reserpine reversal with antidepressant effect led to the theory that MAU inhibition is responsible for imipramine's antidepressant effect. Driven by neuropharmacological theory, non-selective reuptake inhibitors were replaced first by selective norepinephrine reuptake inhibitors, then by selective serotonin reuptake inhibitors, and more recently, by a series of new antidepressants to relieve the stimulation of serotonin-5HT2A receptors and the compensatory decline of dopamine in the brain. Each antidepressant has its own identity, but meta-analyses indicate a widening of the antidepressant response range from 65-70% to 45-79%, and a lowering of the antidepressant threshold from 65% to 45%. Although one can no longer expect that 2 of 3 depressed patients will respond to treatment, the newer antidepressants are better tolerated, because they produce less anticholinergic side effects.
Abstract Background High levels of anxiety are associated with worse outcomes in coronary artery disease patients. Little is known about anxiety levels in patients undergoing coronary procedures. Our ...objective is to examine the levels of anxiety in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during the different phases of hospital stay and to evaluate which patient characteristics are associated with increased anxiety. Methods Patients undergoing CAG or PCI between April 2009 and April 2010 were included in this prospective cohort study. Anxiety levels were measured using the self reported Visual Analogue Scale (VAS) of Anxiety, ranging from 0 to 100. VAS anxiety scores were obtained at hospital intake, pre- and post-procedure, and at hospital discharge. Multivariate linear regression analyses were performed to assess correlations between baseline characteristics and anxiety levels at the different time points. Results In total 2604 patients were included, with 70.4% male participants with a mean age of 65 ± 12 years. VAS anxiety scores were highest pre-procedure (44.2 ± 27.0 mm). Female patients reported a significantly higher pre procedure VAS anxiety score (50.4 ± 26.5) compared to males (41.5 ± 26.8, p = 0.02). Other factors associated with higher levels of anxiety at different time points were age < 65 years, low level of education and an acute primary PCI. Conclusion In the largest cohort to date, we examined anxiety among patients undergoing PCI or CAG was highest immediately around the procedure, particularly in patients aged < 65 years, of female gender, undergoing primary PCI, or with a lower level of education. Better pre-procedural information or pharmacological strategies may reduce anxiety in these patients.
Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations ...for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.
We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.
Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28–4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80–3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10–5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61–5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70–3.00). Sensitivity analyses were consistent with these findings.
In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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Development of the diagnostic concept of schizophrenia (dementia praecox) is traced from the fourth edition of Kraepelin, E., 1893. Ein Kurzes Lehrbuch der Psychiatrie. 4 Aufl. Barth, Lepzig textbook ...to the DSM-IV American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders. Fourth ed. American Psychiatric Association, Washington, 273–316. The differences between the criteria used by Bleuler Bleuler, E., 1911. Dementia Praecox oder Gruppe der Schizophrenien. Deuticke, Leipzig and Schneider Fortschr. Neurol. Psychiatr. 25 (1957) 487 in the diagnosis of schizophrenia are discussed. The nosologic contributions of Kleist Klin. Wochenschr. 2 (1923) 962 and Leonhard Leonhard, K., 1957. Aufteilung der endogenen Psychosen. Akademie, Berlin—which split schizophrenia into two major classes of disease with several forms and subforms—are outlined. Epidemiological findings—which show wide variations in the prevalence of schizophrenia in the general population and in the admission rate of schizophrenics to psychiatric clinics—are presented. Findings in genetic studies are reviewed with special reference to family, twin, and adoption studies which have raised the possibility that heredity plays an important role in the etiology of schizophrenia; mathematical analyses are examined which have ruled out monogenic transmission, as well as molecular genetic investigations indicating that the schizophrenic population is genetically heterogeneous. The relevance of findings with endophenotypes to the genetics of schizophrenia is questioned. The history of pharmacotherapy, neuropharmacology, and psychopharmacology of schizophrenia is outlined. Attention is focused on findings which indicate that the schizophrenic population is pharmacologically heterogenous. It is emphasized that neuropsychopharmacology, through its unique capability of linking the effects of psychotropic drugs to brain structures—encoded by genes which have been identified—offers a pioneering methodology for bridging the gap between the genes and psychiatric nosology. It is pointed out that for the detection of subpopulations within schizophrenia, clinical investigations with antipsychotic drugs have to proceed beyond the demonstration of therapeutic efficacy to the identification of treatment-responsive form(s) of illness. Early findings by Fish L'Encephale 53 (1964) 245 are presented which indicate that affect-laden paraphrenia, one of the three forms of unsystematic schizophrenia in Leonhard Leonhard, K., 1957. Aufteilung der endogenen Psychosen. Akademie, Berlin classification, is the treatment-responsive subpopulation within schizophrenia for typical antipsychotic drugs. It is suggested that if the findings of Fish L'Encephale 53 (1964) 245 could be verified, affect-laden paraphrenia would qualify for molecular genetic research. Another possible subpopulation that might qualify for genetic research is systematic hebephrenia, one of the three forms of systematic hebephrenia. The paper concludes that resolving the heterogeneity of the schizophrenic population would open up a new perspective for genetic research and for the pharmacotherapy of the different illnesses covered up for a century by the diagnostic label of schizophrenia.
Most of the genetic variants that are reported to be associated with common pain phenotypes and analgesic use are common polymorphisms. The objective of our study was to identify new variants and ...investigate less common genetic variants that are usually not included in either small single-gene studies or high-throughput genotyping arrays.
From a cohort of 1075 patients who underwent a scheduled total abdominal hysterectomy, 92 who had higher self-rated pain scores and used more morphine were selected for the re-sequencing of 105 genes.
We identified over 2400 variants in 104 genes. Most were intronic with frequencies >5%. There were 181 novel variants, of which 30 were located in exons: 17 nonsynonymous, 10 synonymous, 2 non-coding RNA, and 1 stop-gain. For known variants that are rare (population frequency <1%), the frequencies of 54 exonic variants and eight intronic variants for the sequenced samples were higher than the weighted frequencies in the Genome Aggregation Database for East and South Asians (
-values ranging from 0.000 to 0.046). Overall, patients who had novel and/or rare variants used more morphine than those who only had common variants.
Our study uncovered novel variants in patients who reported higher pain and used more morphine. Compared with the general population, rare variants were more common in this group.
A
bstract
The electron (anti-)neutrino component of the T2K neutrino beam constitutes the largest background in the measurement of electron (anti-)neutrino appearance at the far detector. The ...electron neutrino scattering is measured directly with the T2K off-axis near detector, ND280. The selection of the electron (anti-)neutrino events in the plastic scintillator target from both neutrino and anti-neutrino mode beams is discussed in this paper. The flux integrated single differential charged-current inclusive electron (anti-)neutrino cross-sections,
dσ/dp
and
dσ/d
cos(
θ
), and the total cross-sections in a limited phase-space in momentum and scattering angle (
p >
300 MeV/c and
θ ≤
45°) are measured using a binned maximum likelihood fit and compared to the neutrino Monte Carlo generator predictions, resulting in good agreement.
In the second half of the 19th century new drugs introduced by the pharmaceutical industry helped lead to the establishment of academic departments in psychiatry. Causal treatment of cerebral ...pellagra by nicotinic acid and cerebral syphilis by penicillin in the first half of the 20th century led to major changes in the diagnostic distribution of psychiatric patients. In the second half of the 20th century with the introduction of a rapidly growing number of psychotropic drugs, pharmacotherapy became the primary form of treatment in mental illness. Psychiatrists today perceive neuropharmacology as one of the basic sciences of psychiatry and psychopharmacology as the bridge between the mode of action and the clinical indications of psychotropic drugs. Pharmacotherapy with psychotropic drugs focused attention on the differential responsiveness to the same drug within the same diagnostic category. Yet, instead of re-evaluating psychiatric nosology and conducting research in psychopathology, a statistical methodology was adopted for the demonstration of therapeutic effectiveness in pharmacologically heterogeneous populations. Employment of consensus-based classifications and psychiatric rating scales in the clinical development of psychotropic drugs led to semi-finished products, which are prescribed indiscriminately. Replacement of single-center clinical trials by multi-center centrally coordinated clinical investigations led to the control of education in pharmacotherapy by the pharmaceutical industry. To separate education from marketing, the identification of the treatment-responsive forms of illness and the delineation of the therapeutic profile of psychotropic drugs are proposed with the employment of a new methodology, the “Composite Diagnostic Evaluation System.” It is postulated that development of a pharmacologically valid psychiatric nosology with the employment of a “nosologic matrix” would provide the pharmaceutical industry with the necessary feedback to develop clinically selective drugs in mental illness and to break the impasse of progress in “translational research” in psychiatry.
To review the historical development of the psychopharmacological treatment of schizophrenia.
A chronological literature review of the clinical practices and theoretical models that have controlled ...drug treatment of schizophrenia at different times.
Effective treatment of schizophrenia was achieved only after the introduction of antipsychotic drugs, in the 1950s, and is still progressing.
Close collaboration between basic neuroscience and careful and informed clinical practice are likely to lead to continued progress.
Despite decades of relevant basic and clinical research, active debate continues about the appropriate extent and duration of benzodiazepine use in the treatment of anxiety and related disorders. The ...primary basis of the controversy seems to be concern among clinicians, regulators, and the public about the dependence potential and the abuse liability of benzodiazepines. This article reports systematically elicited judgments on these issues by a representative panel of 73 internationally recognized experts in the pharmacotherapy of anxiety and depressive disorders, a panel which was constituted by a multistage process of peer nomination. The criterion for inclusion at each stage was the nomination by at least two peers as one of the "professionally most respected physicians of the world with extensive experience and knowledge in the pharmacotherapy of anxiety and depressive disorders." Sixty-six respondents (90%) completed a comprehensive questionnaire covering a wide range of topics relevant to the therapeutic use of benzodiazepines and other medications that might be used for the same purposes. Overall, the expert panel judged that benzodiazepines pose a higher risk of dependence and abuse than most potential substitutes but a lower risk than older sedatives and recognized drugs of abuse. There was little consensus about the relative risk of dependence and abuse among the benzodiazepines. Differences between benzodiazepines with shorter and longer half-lives in inducing withdrawal symptoms are much less clear during tapered than during abrupt discontinuation. There was little agreement about the most important factors contributing to withdrawal symptoms and failure to discontinue benzodiazepines. The pharmacologic properties of the medication may be the most important contributors to withdrawal symptoms. In contrast, the clinical characteristics of the patient may be the most important contributors to failure to discontinue medication. The experts' judgment seems to support the widespread use of benzodiazepines for the treatment of bona fide anxiety disorders, even over long periods. The experts generally viewed dependence and abuse liability as clinical issues amenable to appropriate management, as for other adverse events related to therapy. However, more definitive clinical research on the remaining controversial issues is urgently needed to promote optimal patient care.
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