Treatment seeking for gambling disorder in nationwide register data - observations around a major shift in legislation.

Background: Treatment seeking for gambling disorder is known to be low and there has been a lack of longitudinal research regarding treatment opportunities. The present study aimed to assess possible changes in treatment uptake after a formal introduction of gambling disorder in social services and health care legislations, by using register data, including patient characteristics with respect to socio-demographics and comorbidities. Methods: Nationwide register data were collected for the years 2005-2019, describing diagnoses in specialized out-patient health care and in in-patient hospital care. Numbers and characteristics of patients with gambling disorder were followed longitudinally. Also, a new legislation for treatment by public institutions was introduced in 2018, and data were compared for the years before and after the shift in legislation, both nationally, for each of the three major urban regions, and for the rest of the country. Comparisons were made with respect to concurrent mental health comorbidities, age and gender. Results: The number of out-patient gambling disorder diagnoses increased over time, but without any significant step changes around the shift in legislation. Over time, patients were younger, became more likely to have gambling disorder as their primary diagnosis, and less likely to have mental health comorbidities, whereas gender distribution did not change. Among the smaller group of patients diagnosed in in-patient settings, mental health comorbidity increased over time. Despite gradual changes over time, no changes in demographics were seen around the actual shift in legislation, although the psychiatric comorbidity appeared to increase after this change. Conclusion: After the introduction of gambling disorder in the responsibility of social services and health care settings in Sweden, the number of patients diagnosed with gambling disorder increased only modestly. Likely, further implementation of gambling disorder treatment is required in the health care services. Also, longer longitudinal studies are needed in order to understand to what extent patients not seeking health care treatment are received by municipal social services or remain outside the treatment system.

Early visual cortices reveal interrelated item and category representations in aging.

Neural dedifferentiation, the finding that neural representations tend to be less distinct in older adults compared with younger adults, has been associated with age-related declines in memory performance. Most studies assessing the relation between memory and neural dedifferentiation have evaluated how age impacts the distinctiveness of neural representations for different visual categories (e.g., scenes and objects). However, how age impacts the quality of neural representations at the level of individual items is still an open question. Here, we present data from an age-comparative fMRI study that aimed to understand how the distinctiveness of neural representations for individual stimuli differs between younger and older adults and relates to memory outcomes. Pattern similarity searchlight analyses yielded indicators of neural dedifferentiation at the level of individual items as well as at the category level in posterior occipital cortices. We asked whether age differences in neural distinctiveness at each representational level were associated with inter- and/or intraindividual variability in memory performance. While age-related dedifferentiation at both the item and category level related to between-person differences in memory, neural distinctiveness at the category level also tracked within-person variability in memory performance. Concurrently, neural distinctiveness at the item level was strongly associated with neural distinctiveness at the category level both within and across participants, elucidating a potential representational mechanism linking item- and category-level distinctiveness. In sum, we provide evidence that age-related neural dedifferentiation co-exists across multiple representational levels and is related to memory performance.Significance Statement Age-related memory decline has been associated with neural dedifferentiation, the finding that older adults have less distinctive neural representations than younger adults. This has been mostly shown for category information, while evidence for age differences in the specificity of item representations is meager. We used pattern similarity searchlight analyses to find indicators of neural dedifferentiation at both levels of representation (category and item) and linked distinctiveness to memory performance. Both item- and category-level dedifferentiation in the calcarine cortex were related to interindividual differences in memory performance, while category-level distinctiveness further tracked intraindividual variability. Crucially, neural distinctiveness was strongly tied between the item and category levels, indicating that intersecting representational properties of posterior occipital cortices reflect both individual exemplars and categories.

Long term survival and abnormal liver fat accumulation in mice with specific thymidine kinase 2 deficiency in liver tissue.

Deficiency in thymidine kinase 2 (TK2) causes mitochondrial DNA depletion. Liver mitochondria are severely affected in Tk2 complete knockout models and have been suggested to play a role in the pathogenesis of the Tk2 knockout phenotype, characterized by loss of hypodermal fat tissue, growth retardation and reduced life span. Here we report a liver specific Tk2 knockout (KO) model to further study mechanisms contributing to the phenotypic changes associated with Tk2 deficiency. Interestingly, the liver specific Tk2 KO mice had a normal life span despite a much lower mtDNA level in liver tissue. Mitochondrial DNA encoded peptide COXI did not differ between the Tk2 KO and control mice. However, the relative liver weight was significantly increased in the male Tk2 KO mouse model. Histology analysis indicated an increased lipid accumulation. We conclude that other enzyme activities can partly compensate Tk2 deficiency to maintain mtDNA at a low but stable level throughout the life span of the liver specific Tk2 KO mice. The lower level of mtDNA was sufficient for survival but led to an abnormal lipid accumulation in liver tissue.

Metabolite interactions in the bacterial Calvin cycle and implications for flux regulation.

Metabolite-level regulation of enzyme activity is important for microbes to cope with environmental shifts. Knowledge of such regulations can also guide strain engineering for biotechnology. Here we apply limited proteolysis-small molecule mapping (LiP-SMap) to identify and compare metabolite-protein interactions in the proteomes of two cyanobacteria and two lithoautotrophic bacteria that fix CO2 using the Calvin cycle. Clustering analysis of the hundreds of detected interactions shows that some metabolites interact in a species-specific manner. We estimate that approximately 35% of interacting metabolites affect enzyme activity in vitro, and the effect is often minor. Using LiP-SMap data as a guide, we find that the Calvin cycle intermediate glyceraldehyde-3-phosphate enhances activity of fructose-1,6/sedoheptulose-1,7-bisphosphatase (F/SBPase) from Synechocystis sp. PCC 6803 and Cupriavidus necator in reducing conditions, suggesting a convergent feed-forward activation of the cycle. In oxidizing conditions, glyceraldehyde-3-phosphate inhibits Synechocystis F/SBPase by promoting enzyme aggregation. In contrast, the glycolytic intermediate glucose-6-phosphate activates F/SBPase from Cupriavidus necator but not F/SBPase from Synechocystis. Thus, metabolite-level regulation of the Calvin cycle is more prevalent than previously appreciated.

Effects of Aging on Successful Object Encoding: Enhanced Semantic Representations Compensate for Impaired Visual Representations.

Although episodic memory and visual processing decline substantially with healthy aging, semantic knowledge is generally spared. There is evidence that older adults' spared semantic knowledge can support episodic memory. Here, we used functional magnetic resonance imaging (fMRI) combined with representational similarity analyses (RSAs) to examine how novel visual and preexisting semantic representations at encoding predict subjective memory vividness at retrieval. Eighteen young and seventeen older adults (female and male participants) encoded images of objects during fMRI scanning and recalled these images while rating the vividness of their memories. After scanning, participants discriminated between studied images and similar lures. RSA based on a deep convolutional neural network and normative concept feature data were used to link patterns of neural activity during encoding to visual and semantic representations. Relative to young adults, the specificity of activation patterns for visual features was reduced in older adults, consistent with dedifferentiation. However, the specificity of activation patterns for semantic features was enhanced in older adults, consistent with hyperdifferentiation. Despite dedifferentiation, visual representations in early visual cortex (EVC) predicted high memory vividness in both age groups. In contrast, semantic representations in lingual gyrus (LG) and fusiform gyrus (FG) were associated with high memory vividness only in the older adults. Intriguingly, data suggests that older adults with lower specificity of visual representations in combination with higher specificity of semantic representations tended to rate their memories as more vivid. Our findings suggest that memory vividness in aging relies more on semantic representations over anterior regions, potentially compensating for age-related dedifferentiation of visual information in posterior regions.SIGNIFICANCE STATEMENT Normal aging is associated with impaired memory for events while semantic knowledge might even improve. We investigated the effects of aging on the specificity of visual and semantic information in the brain when viewing common objects and how this information enables subsequent memory vividness for these objects. Using functional magnetic resonance imaging (fMRI) combined with modeling of the stimuli we found that visual information was represented with less specificity in older than young adults while still supporting memory vividness. In contrast semantic information supported memory vividness only in older adults and especially in those individuals that had the lowest specificity of visual information. These findings provide evidence for a spared semantic memory system increasingly recruited to compensate for degraded visual representations in older age.

Personal experiences of suicidality in women with gambling disorder - A qualitative interview study.

Background: Gambling disorder is associated with increased suicidality, especially in women who also are more likely to have psychiatric comorbid disorders and more often have experiences of traumatic life events. Although suicidality is increased and several risk factors have been identified, knowledge of the suicidal process is lacking, especially for women. Aim: To explore the lived experiences of suicidality in women with gambling disorder and to investigate potential factors involved in the development of suicidality. Method: Semi-structured interviews were held with seven women with experiences of gambling disorder and suicidality in Malmö, Sweden between November 2021 and June 2022, when saturation was reached. Interviews were audio-recorded, transcribed, and coded in NVivo. Qualitative content analysis was used to build categories and themes. Results: Several women had experienced suicidality before developing gambling disorder and gambling-related suicidality. However, for some, suicidality had appeared seemingly only due to the gambling disorder. Suicidality ranged from ideation to severe suicide attempts. Three themes of factors modulating suicidality related to gambling were found; a) guilt shame and self-stigmatization, b) loss of control/chaotic life circumstances, and c) social consequences/fear of guilt and shame from others. Conclusion: More research on the experience of suicidality in women with gambling disorder is needed. Attempts to address self-stigmatization, guilt, and shame in women with gambling disorder and society at large as well as aiding women to regain a sense of control over their economy and gambling may be ways to reduce suicidality.

Meanings and functions of different types of heart images in the communication of doctors and patients.

Images in medical communication are appreciated by both professionals and patients, but we know little about how they are actually used in clinical practice and in the learning processes of patients. This qualitative study investigates the use and the meaning potential of two different types of heart images: the hand-drawn doctor's sketch and the digital illustration from the web. The analysis starts with how these are recontextualised in social media, tracks them back to their original contexts and finally explores their material resources. The analytical perspective is that of social semiotics and multimodal discourse and interaction analysis. While the hand-drawn sketch is recontextualised as a witness of the specific consultation, the digital illustration is used to focus on the heart defect as such. It is also shown how the act of drawing works as a means for framing and structuring the consultation, slowing down the pace and reducing context and detail and thus focussing on what is uniquely relevant. While the digital and more realistic illustration is technically neutral and objective and is free from unique context, the drawing on paper is physically tied to its context of origin, which is also its main resource.

Gambling and COVID-19: Swedish national gambling data from a state-owned gambling sports and casino operator.

Background and aims: The lockdown of sports and gambling venues during the coronavirus disease 2019 (COVID-19) pandemic caused a fear of increased gambling on other online gambling types, with a risk for transfer to more addictive gambling than otherwise. This study aimed to estimate changes in gambling activity during COVID-19-affected periods among all gamblers at a Swedish state-owned gambling operator and to analyse observable sex differences. Methods: This study included gambling tracking data from the Swedish state-owned gambling operator Svenska Spel Sports & Casino (sports betting, online bingo, casino and poker). All individuals (n = 616,245) who gambled at least once from February 10 to July 19, 2020, were included. The study period was divided into four periods according to their expected level of COVID-19 impact on gambling opportunities: one pre-COVID period and three COVID-affected periods (sports cancellation, emerging return of sports, substantial return of sports). Results: Sports betting experienced an apparent decrease, followed by a gradual normalization and an end level substantially below prepandemic levels. For online bingo, gambling levels increased upon sports interruption and then decreased with the return to normality in sports events but remained higher than baseline levels. We observed a similar trend for online poker during the interruption of sports, but with a lower level than baseline levels when sports events normalized. We noticed a trend favouring online casinos during the sports interruption period regarding gambling intensity but not wagering levels. Discussion and conclusions: Dramatic changes in the content of the gambling market may divert some gamblers to other gambling types, but maintained effects could not be demonstrated.

The Roles of Nicotinamide Adenine Dinucleotide Phosphate Reoxidation and Ammonium Assimilation in the Secretion of Amino Acids as Byproducts of Clostridium thermocellum.

Clostridium thermocellum is a cellulolytic thermophile that is considered for the consolidated bioprocessing of lignocellulose to ethanol. Improvements in ethanol yield are required for industrial implementation, but the incompletely understood causes of amino acid secretion impede progress. In this study, amino acid secretion was investigated via gene deletions in ammonium-regulated, nicotinamide adenine dinucleotide phosphate (NADPH)-supplying and NADPH-consuming pathways as well as via physiological characterization in cellobiose-limited or ammonium-limited chemostats. First, the contribution of the NADPH-supplying malate shunt was studied with strains using either the NADPH-yielding malate shunt (Δppdk) or a redox-independent conversion of PEP to pyruvate (Δppdk ΔmalE::Peno-pyk). In the latter, branched-chain amino acids, especially valine, were significantly reduced, whereas the ethanol yield increased from 46 to 60%, suggesting that the secretion of these amino acids balances the NADPH surplus from the malate shunt. The unchanged amino acid secretion in Δppdk falsified a previous hypothesis on an ammonium-regulated PEP-to-pyruvate flux redistribution. The possible involvement of another NADPH-supplier, namely, NADH-dependent reduced ferredoxin:NADP+ oxidoreductase (nfnAB), was also excluded. Finally, the deletion of glutamate synthase (gogat) in ammonium assimilation resulted in the upregulation of NADPH-linked glutamate dehydrogenase activity and decreased amino acid yields. Since gogat in C. thermocellum is putatively annotated as ferredoxin-linked, a claim which is supported by the product redistribution observed in this study, this deletion likely replaced ferredoxin with NADPH in ammonium assimilation. Overall, these findings indicate that a need to reoxidize NADPH is driving the observed amino acid secretion, likely at the expense of the NADH needed for ethanol formation. This suggests that metabolic engineering strategies that simplify the redox metabolism and ammonium assimilation can contribute to increased ethanol yields. IMPORTANCE Improving the ethanol yield of C. thermocellum is important for the industrial implementation of this microorganism in consolidated bioprocessing. A central role of NADPH in driving amino acid byproduct formation was demonstrated by eliminating the NADPH-supplying malate shunt and separately by changing the cofactor specificity in ammonium assimilation. With amino acid secretion diverting carbon and electrons away from ethanol, these insights are important for further metabolic engineering to reach industrial requirements on ethanol yield. This study also provides chemostat data that are relevant for training genome-scale metabolic models and for improving the validity of their predictions, especially considering the reduced degree-of-freedom in the redox metabolism of the strains generated here. In addition, this study advances the fundamental understanding on the mechanisms underlying amino acid secretion in cellulolytic Clostridia as well as on the regulation and cofactor specificity in ammonium assimilation. Together, these efforts aid in the development of C. thermocellum for the sustainable consolidated bioprocessing of lignocellulose to ethanol with minimal pretreatment.

Evaluation of measures related to dosimetric uncertainty of VMAT plans.

Dosimetric uncertainty is most often not included in the process of creating and selecting plans for treatment. Treatment planning and the physician's choice of treatment plan is instead often based only on evaluation of clinical goals of the calculated absorbed dose distribution. Estimation of the dosimetric uncertainty could potentially have impact in the process of comparing and selecting volumetric modulated arc therapy (VMAT) plans. In this study, different measures for estimation of dosimetric uncertainty based on treatment plan parameters for plans with similar dose distributions were evaluated. VMAT plans with similar dose distributions but with different treatment plan designs were created using three different optimization methods for each of ten patient cases (tonsil and prostate cancer). Two plans were optimized in Eclipse, one with and one without the use of aperture shape controller, and one plan was optimized in RayStation. The studied measures related to dosimetric uncertainty of treatment plans were aperture-based complexity metric analysis, investigation of modulation level of multi leaf collimator leaves, gantry speed and dose rate, quasi-3D measurements and evaluation of simulations of realistic delivery variations. The results showed that there can be variations in dosimetric uncertainty for treatment plans with similar dose distributions. Dosimetric uncertainty assessment could therefore have impact on the choice of plan to be used for treatment and lead to a decrease in the uncertainty level of the delivered absorbed dose distribution. This study showed that aperture shape complexity had a larger impact on dosimetric uncertainty compared to modulation level of MLC, gantry speed and dose rate.

Subjective and objective evaluation of masticatory function in patients with bimaxillary implant-supported prostheses.

BACKGROUND: People perform poorly in masticatory function tests despite well-functioning prostheses. However, it is unclear whether there is an agreement between subjective and objective measures of mastication. OBJECTIVES: To investigate the association between subjective and objective measures of masticatory function in patients with bimaxillary implant-supported prostheses. MATERIALS AND METHODS: An experimental group (n = 25, age = 70.6 ± 7.5 years, eight women) with bimaxillary implant-supported fixed prostheses and a control group (n = 25, age = 69.0 ± 5.3, 13 women) with natural dentition were recruited. The participants in the experimental group were included if they had been using the prosthesis for at least a year and had no obvious complaints with their prostheses. The control group was people with natural dentition and without any prostheses or complaints related to the masticatory system. The masticatory function was evaluated objectively with food comminution and mixing ability tests, and subjectively with jaw function limitation scale (JLFS) and oral health impact profile (OHIP). RESULTS: The experimental group performed poorly in both objective tests (p < .001). However, there was no significant differences between the two groups in total JFLS (p = .114) and OHIP (p = .312) scores. Though, there were certain positive correlations between the food comminution test and JFLS subdomains in the control group, and a positive correlation between food comminution test and specific subdomains of OHIP in the experimental group indicating poor correlation between the subjective and objective measures. CONCLUSION: Although patients with implant prostheses show poor masticatory performance, there is no agreement in the objective and subjective measures of mastication.

Altered alpha/beta desynchronization during item-context binding contributes to the associative deficit in older age.

It is proposed that older adults have difficulties to bind item and context and to recruit deep, elaborative processing during encoding. Senescent changes in the oscillatory foundations of these processes are currently unclear. We recorded electroencephalography during item-context memory formation in younger (n = 57) and older (n = 55) adults. At test, we assessed memory for the items and the item-context pairs and examined encoding-related activity based on how much information was recovered at retrieval (miss < item-only < pair). Item memory was comparable between age groups while pair memory was reduced in the older adults. Theta synchronization and alpha/beta desynchronization increased linearly with the amount of information available. Single-trial theta power could not predict subsequent item memory, but predicted pair memory in an age-invariant manner, in line with a mechanism supporting associative memory. In contrast, single-trial alpha/beta power predicted both item and pair memory, in line with a mechanism reflecting the depth of information processing, and predicted pair memory less well in the older than the younger adults. Thus, theta and alpha/beta oscillations contribute differently in shaping the contents of memories and reduced processing capacity contributes to episodic memory decline in older age.

A trans-omics assessment of gene-gene interaction in early-stage NSCLC.

Epigenome-wide gene-gene (G × G) interactions associated with non-small-cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G × G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175 775 G × G interactions with PBonferroni ≤ 0.05 in the discovery phase of epigenomic analysis; among them, 15 534 were confirmed with P ≤ 0.05 in the validation phase. In the second step, we further performed a functional validation for these G × G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G × G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G × G interactions using the trans-omics analysis, which had significant (P ≤ 0.05) epigenetic cis-regulation of transcription and robust G × G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855 × cg23937960 (ßinteraction  = 0.018, P = 1.87 × 10-12 ), which mapped to RELA × HLA-G (ßinteraction  = 0.218, P = 8.82 × 10-11 ) and cg08872738 × cg27077312 (ßinteraction  = -0.010, P = 1.16 × 10-11 ), which mapped to TUBA1B × TOMM40 (ßinteraction =-0.250, P = 3.83 × 10-10 ). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P = 0.034) mediated through transcriptional expression. These statistically significant trans-omics G × G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G × G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.

Dosimetric effects of respiratory motion during stereotactic body radiation therapy of lung tumors.

BACKGROUND: Respiratory-induced lung tumor motion may affect the delivered dose in stereotactic body radiation therapy (SBRT). Previous studies are often based on phantom studies for one specific treatment technique. In this study, the dosimetric effect of tumor motion was quantified in real patient geometries for different modulated treatments and tumor motion amplitudes for lung-SBRT. MATERIAL AND METHODS: A simulation method using deformable image registrations and 4-dimensional computed tomographies (4DCT) was developed to assess the dosimetric effects of tumor motion. The method was evaluated with ionization chamber and Gafchromic film measurements in a thorax phantom and used to simulate the effect for 15 patients with lung tumors moving 7.3-27.4 mm. Four treatment plans with different complexities were created for each patient and the motion-induced dosimetric effect to the gross tumor volume (GTV) was simulated. The difference between the planned dose to the static tumor and the simulated delivered dose to the moving tumor was quantified for the near minimum (D98%), near maximum (D2%) and mean dose (Dmean) to the GTV as well as the largest observed local difference within the GTV (Maxdiff). RESULTS: No correlation was found between the dose differences and the tumor motion amplitude or plan complexity. However, the largest deviations were observed for tumors moving >15.0 mm. The simulated delivered dose was within 2.5% from the planned dose for D98% (tumors moving <15 mm) and within 3.3% (tumors moving >15 mm). The corresponding values were 1.7% vs. 6.4% (D2%); 1.7% vs. 2.4% (Dmean) and 8.9% vs. 35.2% (Maxdiff). Using less complex treatment techniques minimized Maxdiff for tumors moving >15.0 mm. CONCLUSION: The dosimetric effects of respiratory-induced motion during lung SBRT are patient and plan specific. The magnitude of the dosimetric effect cannot be assessed solely based upon tumor motion amplitude or plan complexity.

Crime-Specific Recidivism in Criminal Justice Clients with Substance Use-A Cohort Study.

Criminal recidivism is a major global concern. There is a well-known association between substance use disorders and offending. Yet, little is known about crime-specific recidivism. The aim of this study was to investigate the relationship between specific substance use and crime-specific recidivism. The study is based on 4207 Swedish prison clients with substance use assessed with Addiction Severity Index interviews between 2001 and 2006. Clients were followed for an average of 2.7 years. Risk factors for criminal recidivism were assessed with the Cox regression analysis. Sixty-eight percent of the clients returned to the criminal justice system. Apart from well-known risk factors such as male gender and young age, amphetamine, injection drug use, prior prosecution for violent and property crime, as well as homelessness and psychiatric problems, were risk factors for criminal recidivism. Sedatives and cannabis were, in this setting, negative risk factors for general recidivism. Age, heroin and injection drug use elevated the risks of recidivism to property and drug crime. Alcohol was associated with violent recidivism. When analysing different categories of crime separately, risk factors differed substantially. This further highlights the need for crime-specific research. Identifying crime-specific risk factors should be an important part of improving rehabilitation into society after imprisonment and hopefully decrease recidivism.

Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2.

Thymidine kinase 2 (TK2) deficiency in humans leads to a myopathic form of mitochondrial DNA (mtDNA) deficiency. Here we present a skeletal and cardiac muscle specific TK2 knockout mouse (mTk2 KO). The mice showed dilated hearts and markedly reduced adipose tissue during week 12 to 16. A severe decrease of mtDNA was found only in skeletal muscle and heart tissue in mTk2 KO mice. Expression analysis of key metabolic genes of 16 weeks knockout mice showed significant changes of genes involved in lipid metabolism, with different patterns in heart and skeletal muscle. Our study further suggests that lipoprotein lipase (LPL) from liver supports the metabolism when heart and skeletal muscle were impaired due to mitochondrial dysfunction. The angiotensin-converting enzyme 2 (ACE2), which is involved in glucose homeostasis, was also affected by mtDNA deficiency in our study. Interestingly, both the gene and protein expression of ACE2 were increased in cardiac tissue of mTk2 KO mice. Since ACE2 is a receptor for the SARS-CoV-2 virus, its regulation in relation to mitochondrial function may have important clinical implications.

Identifying targets for increased biogas production through chemical and organic matter characterization of digestate from full-scale biogas plants: what remains and why?

BACKGROUND: This study examines the destiny of macromolecules in different full-scale biogas processes. From previous studies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential, but the factors dictating the size and composition of this residual fraction and how they correlate with the residual methane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of the composition of residual digestate fractions and to understand how they correlate with various operational and chemical parameters. The organic composition of both the substrates and digestates from nine biogas plants operating on food waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked to substrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity. RESULTS: Carbohydrates represented the largest fraction of the total VS (32-68%) in most substrates. However, in the digestates protein was instead the most abundant residual macromolecule in almost all plants (3-21 g/kg). The degradation efficiency of proteins generally lower (28-79%) compared to carbohydrates (67-94%) and fats (86-91%). High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from the substrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradation efficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates also triggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kg VS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mg NH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative to the slow digestion of agricultural waste and manure. CONCLUSIONS: Operation at unstable conditions was one reason for the high residual macromolecule content and high RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteins represents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment or post-digestion of digestates, targeting microbial biomass or recalcitrant protein fractions, is a potential way to achieve increased protein degradation.

Head and neck cancer patient positioning using synthetic CT data in MRI-only radiation therapy.

PURPOSE: The accuracy and precision of patient positioning is crucial in radiotherapy; however, there are no publications available using synthetic computed tomography (sCT) that evaluate rotations in head and neck (H&N) patients positioning or the effect of translation and rotation combined. The aim of this work was to evaluate the differences between using sCT with the CT for 2D- and 3D-patient positioning in a magnetic resonance imaging (MRI)-only workflow. METHODS: This study included 14 H&N cancer patients, with generated sCT data (MRI Planner v2.2) and the CT deformably registered to the MRI. Patient positioning was evaluated by comparing sCT against CT data: 3D cone beam CT (CBCT) was registered to the deformed CT (dCT) and sCT in six degrees of freedom (DoF) with a rigid auto-registration algorithm and bone threshold, and 2D deformed digital reconstructed radiographs (dDRR) and synthetic DRRs (sDRR) were manually registered to orthogonal projections in five DoF by six blinded observers. The difference in displacement in all DoF were calculated for dCT and sCT, as well as for dDRR and sDRR. The interobserver variation was evaluated by separate application of the paired dDRR and sDRR registration matrices to the original coordinates of the planning target volume (PTV) structures and calculation of the Euclidean distance between the corresponding points. The Dice similarity coefficient (DSC) was calculated between dDRR/sDRR-registered PTVs. RESULTS: The mean difference in patient positioning using CBCT was <0.7 mm and <0.3° and using orthogonal projections <0.4 mm and <0.2° in all directions. The maximum Euclidean distance was 5.1 mm, the corresponding mean (1SD) Euclidean distance and mean DSC were 3.5 ± 0.7 mm and 0.93, respectively. CONCLUSIONS: This study shows that the sCT-based patient positioning gives a comparable result with that based on CT images, allowing sCT to replace CT as reference for patient treatment positioning.

Out of Rhythm: Compromised Precision of Theta-Gamma Coupling Impairs Associative Memory in Old Age.

Episodic memory declines with advancing adult age. This decline is particularly pronounced when associations between items and their contexts need to be formed. According to theories of neural communication, the precise coupling of gamma power to the phase of the theta rhythm supports associative memory formation. To investigate whether age differences in associative memory are related to compromised theta-gamma coupling, we took EEG recordings during the encoding phase of an item-context association task. Fifty-eight younger (33 females) and 55 older (24 females) adults studied pictures of objects superimposed on background scenes. In a recognition test, objects were presented on old or new backgrounds, and participants responded if they had seen (1) the object and (2) the object/scene pair. Theta-gamma coupling supported pair memory formation in both age groups. Whereas pair memory was associated with coupling closer to the peak of the theta rhythm, item-only memory was associated with a deviation in phase angle relative to pair memory. Furthermore, a stable relation between coupling phase and pair memory performance demonstrated that coupling closer to the peak is beneficial for associative memory. Critically, older adults' lower pair memory was accompanied by a shift in coupling phase relative to that of younger adults. In concert, the present results are consistent with the hypothesis that decrements in the temporal precision with which gamma power is coupled to a specific theta phase underlie the decline of associative memory in normal cognitive aging.SIGNIFICANCE STATEMENT According to prominent theories of neural communication, the precise coordination of oscillatory activity enables the formation of associative memories. We propose that normal cognitive aging impairs associative memory formation by compromising the temporal precision of neural communication. We show that the coupling of high-frequency gamma power to low-frequency theta phase supports associative memory formation in both younger and older adults, with coupling closer to the theta peak benefitting memory performance. However, compared with younger adults, the coupling phase angle is shifted in time and is more variable in the older adults. We conclude that alterations in the precise timing of theta-gamma coupling contribute to adult age differences in associative memory.