Mental state of demoralisation across diverse clinical settings: A systematic review, meta-analysis and proposal for its use as a ‘specifier’ in mental illness

Objective: Demoralisation is a state of poor coping characterised by low morale, hopelessness, subjective incompetence, and loss of meaning and purpose in life. While studied extensively in oncology and palliative care, there has been recent exploration in broader medical and mental health settings. The aim was to investigate the prevalence of demoralisation and associated sociodemographic and psychological factors across these clinical settings. Method: Six electronic databases were used to locate articles from January 2014 to March 2020. A pre-publication update of non-oncology populations was completed in September 2021. The review has been reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled prevalence of demoralisation was determined through % prevalence and mean demoralisation score; this was synthesised through meta-analysis of single means to determine pooled mean prevalence of Demoralisation Scale scores using the ‘R’ statistical software. Results: Demoralisation has been examined in 52 studies (n = 11,670) and found to be prevalent in 24–35% of oncology and non-oncology, including mental health, populations. The mean score on the Demoralisation Scale was 24.3 (95% confidence interval, CI = [21.3, 27.3]). There was evidence of divergent validity in addition to significant comorbidity between depression, demoralisation and suicidal ideation. Burdensome physical symptoms, and psychological and demographic factors are strongly correlated with demoralisation. Conclusion: There remains a need to recognise demoralisation in various clinical and cultural settings and to strongly consider its inclusion as a ‘specifier’ within formal nosological systems for adjustment and depressive disorders. This is important to initiate targeted interventions and prevent significant morbidity

Multiscale temporal response of salt intrusion to transient river and ocean forcing

Salt intrusion in surface waters endangers freshwater availability, influences water quality, and affects estuarine ecosystem services with high economic and social values. Salt transport and the resulting salinity distributions result from the non-linear interactions between salt and water dynamics. Estuaries are often considered under (quasi)-steady assumption or by focusing on specific timescales. Our understanding of their temporal multiscale response to transient forcing is limited, which hinders the implementation of effective mitigation strategies. We apply wavelet analyses to quantify the variability of salt intrusion from hourly to seasonal timescales and unravel the temporal variability of its response across scales. We focus on an estuary that undergoes significant transient forcing, the Modaomen estuary in the Pearl River Delta, and apply the wavelet analyses to year-long data generated by a coastal ocean numerical model. Our results show that this estuary responds to changes in tidal and riverine forcing throughout the year over interwoven timescales. Our results highlight the temporal variability of the salt intrusion response time both within a given regime and for the transition between regimes. They also suggest that tides control the response time more strongly than river discharge, even though river discharge determines the magnitude of the salt intrusion, and thus modulates the evolution of the salt intrusion response time. We propose a broadly applicable framework to calculate response times with simple data. These results can provide a first-order guidance for design and implementation of estuarine management strategies and mitigation measures that ensure water access and facilitate sustainable development

KT&G : From Korean monopoly to ‘a global name in the tobacco industry’

Until the late 1980s, the former South Korean tobacco monopoly KT&G was focused on the protected domestic market. The opening of the market to foreign competition, under pressure from the U.S. Trade Representative, led to a steady erosion of market share over the next 10 years. Drawing on company documents and industry sources, this paper examines the adaptation of KT&G to the globalization of the South Korean tobacco industry since the 1990s. It is argued that KT&G has shifted from a domestic monopoly to an outward-looking, globally oriented business in response to the influx of transnational tobacco companies. Like other high-income countries, South Korea has also seen a decline in smoking prevalence as stronger tobacco control measures have been adopted. Faced with a shrinking domestic market, KT&G initially focused on exporting Korean-manufactured cigarettes. Since the mid-2000s, a broader global business strategy has been adopted including the building of overseas manufacturing facilities, establishing strategic partnerships and acquiring foreign companies. Trends in KT&G sales suggest an aspiring transnational tobacco company poised to become a major player in the global tobacco market. This article is part of the special issue \u27The emergence of Asian tobacco companies: Implications for global health governance\u27

Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

<p>Abstract</p> <p>Background</p> <p>The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters.</p> <p>Methods</p> <p>Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76) under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate.</p> <p>Results and Discussion</p> <p>Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2) cows (LL yielded more than LV cows) in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows) suggesting a better energy status of LL cows.</p> <p>There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows). IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows). IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows.</p> <p>Conclusion</p> <p>The GH and IGF-I genotypes had no substantial effect on productive parameters, although IGF-I genotype affected calving-first service interval in primiparous cows. Besides, these genotypes may modify the endocrine/metabolic profiles of the transition dairy cow under grazing conditions.</p

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P  0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1

Locus-specific control of DNA resection and suppression of subtelomeric <i>VSG </i>recombination by HAT3 in the African trypanosome

The African trypanosome, Trypanosoma brucei, is a parasitic protozoan that achieves antigenic varia-tion through DNA-repair processes involving Variant Surface Glycoprotein (VSG) gene rearrangements at subtelomeres. Subtelomeric suppression of DNA re-pair operates in eukaryotes but little is known about these controls in trypanosomes. Here, we identify a trypanosome histone acetyltransferase (HAT3) and a deacetylase (SIR2rp1) required for efficient RAD51-dependent homologous recombination. HAT3 and SIR2rp1 were required for RAD51-focus assembly and disassembly, respectively, at a chromosome-internal locus and a synthetic defect indicated dis-tinct contributions to DNA repair. Although HAT3 pro-moted chromosome-internal recombination, it sup-pressed subtelomeric VSG recombination, and these locus-specific effects were mediated through dif-ferential production of ssDNA by DNA resection; HAT3 promoted chromosome-internal resection but suppressed subtelomeric resection. Consistent with the resection defect, HAT3 was specifically required for the G2-checkpoint response at a chromosome-internal locus. HAT3 also promoted resection at a second chromosome-internal locus comprising tandem-duplicated genes. We conclude that HAT3 and SIR2rp1 can facilitate temporally distinct steps in DNA repair. HAT3 promotes ssDNA formation and recombination at chromosome-internal sites but has the opposite effect at a subtelomeric VSG. These locus-specific controls reveal compartmentalization of the T. brucei genome in terms of the DNA-damage response and suppression of antigenic variation by HAT3

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Aging Differentially Affects Multiple Aspects of Vesicle Fusion Kinetics

How fusion pore formation during exocytosis affects the subsequent release of vesicle contents remains incompletely understood. It is unclear if the amount released per vesicle is dependent upon the nature of the developing fusion pore and whether full fusion and transient kiss and run exocytosis are regulated by similar mechanisms. We hypothesise that if consistent relationships exist between these aspects of exocytosis then they will remain constant across any age. Using amperometry in mouse chromaffin cells we measured catecholamine efflux during single exocytotic events at P0, 1 month and 6 months. At all ages we observed full fusion (amperometric spike only), full fusion preceded by fusion pore flickering (pre-spike foot (PSF) signal followed by a spike) and pure “kiss and run” exocytosis (represented by stand alone foot (SAF) signals). We observe age-associated increases in the size of all 3 modes of fusion but these increases occur at different ages. The release probability of PSF signals or full spikes alone doesn't alter across any age in comparison with an age-dependent increase in the incidence of “kiss and run” type events. However, the most striking changes we observe are age-associated changes in the relationship between vesicle size and the membrane bending energy required for exocytosis. Our data illustrates that vesicle size does not regulate release probability, as has been suggested, that membrane elasticity or flexural rigidity change with age and that the mechanisms controlling full fusion may differ from those controlling “kiss and run” fusion

Marine organic matter in the remote environment of the Cape Verde islands-an introduction and overview to the MarParCloud campaign

The project MarParCloud (Marine biological production, organic aerosol Particles and marine Clouds: a process chain) aims to improve our understanding of the genesis, modification and impact of marine organic matter (OM) from its biological production, to its export to marine aerosol particles and, finally, to its ability to act as ice-nucleating particles (INPs) and cloud condensation nuclei (CCN). A field campaign at the Cape Verde Atmospheric Observatory (CVAO) in the tropics in September-October 2017 formed the core of this project that was jointly performed with the project MARSU (MARine atmospheric Science Unravelled). A suite of chemical, physical, biological and meteorological techniques was applied, and comprehensive measurements of bulk water, the sea surface microlayer (SML), cloud water and ambient aerosol particles collected at a ground-based and a mountain station took place. Key variables comprised the chemical characterization of the atmospherically relevant OM components in the ocean and the atmosphere as well as measurements of INPs and CCN. Moreover, bacterial cell counts, mercury species and trace gases were analyzed. To interpret the results, the measurements were accompanied by various auxiliary parameters such as air mass back-trajectory analysis, vertical atmospheric profile analysis, cloud observations and pigment measurements in seawater. Additional modeling studies supported the experimental analysis. During the campaign, the CVAO exhibited marine air masses with low and partly moderate dust influences. The marine boundary layer was well mixed as indicated by an almost uniform particle number size distribution within the boundary layer. Lipid biomarkers were present in the aerosol particles in typical concentrations of marine background conditions. Accumulation-and coarse-mode particles served as CCN and were efficiently transferred to the cloud water. The ascent of ocean-derived compounds, such as sea salt and sugar-like compounds, to the cloud level, as derived from chemical analysis and atmospheric transfer modeling results, denotes an influence of marine emissions on cloud formation. Organic nitrogen compounds (free amino acids) were enriched by several orders of magnitude in submicron aerosol particles and in cloud water compared to seawater. However, INP measurements also indicated a significant contribution of other non-marine sources to the local INP concentration, as (biologically active) INPs were mainly present in supermicron aerosol particles that are not suggested to undergo strong enrichment during ocean-atmosphere transfer. In addition, the number of CCN at the supersaturation of 0.30 % was about 2.5 times higher during dust periods compared to marine periods. Lipids, sugar-like compounds, UV-absorbing (UV: ultraviolet) humic-like substances and low-molecularweight neutral components were important organic compounds in the seawater, and highly surface-active lipids were enriched within the SML. The selective enrichment of specific organic compounds in the SML needs to be studied in further detail and implemented in an OM source function for emission modeling to better understand transfer patterns, the mechanisms of marine OM transformation in the atmosphere and the role of additional sources. In summary, when looking at particulate mass, we see oceanic compounds transferred to the atmospheric aerosol and to the cloud level, while from a perspective of particle number concentrations, sea spray aerosol (i.e., primary marine aerosol) contributions to both CCN and INPs are rather limited. © Author(s) 2020