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Stem cells give rise to the entirety of cells within an organ. Maintaining stem cell identity and coordinately regulating stem cell divisions is crucial for proper development. In plants, mobile proteins, such as WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), regulate divisions in the root stem cell niche. However, how these proteins coordinately function to establish systemic behaviour is not well understood. We propose a non-cell autonomous role for WOX5 in the cortex endodermis initial (CEI) and identify a regulator, ANGUSTIFOLIA (AN3)/GRF-INTERACTING FACTOR 1, that coordinates CEI divisions. Here, we show with a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling that quiescent center (QC) and CEI divisions have different dynamics. Specifically, by combining continuous models to describe regulatory networks and agent-based rules, we model systemic behaviour, which led us to predict cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and experimentally validate CEI cell divisions. Conclusively, our results show an interdependency between CEI and QC divisions.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
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Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.
Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.
CAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.
We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.
Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.
Subjective cognitive difficulties are common in mental illness and have a negative impact on role functioning. Little is understood about subjective cognition and the longitudinal relationship with depression and anxiety symptoms in young people.
To examine the relationship between changes in levels of depression and anxiety and changes in subjective cognitive functioning over 3 months in help-seeking youth.
This was a cohort study of 656 youth aged 12–25 years attending Australian headspace primary mental health services. Subjective changes in cognitive functioning (rated as better, same, worse) reported after 3 months of treatment was assessed using the Neuropsychological Symptom Self-Report. Multivariate multinomial logistic regression analysis was conducted to evaluate the impact of baseline levels of and changes in depression (nine-item Patient Health Questionnaire; PHQ9) and anxiety symptoms (seven-item Generalised Anxiety Disorder scale; GAD7) on changes in subjective cognitive function at follow-up while controlling for covariates.
With a one-point reduction in PHQ9 at follow-up, there was an estimated 11–18% increase in ratings of better subjective cognitive functioning at follow-up, relative to stable cognitive functioning. A one-point increase in PHQ9 from baseline to follow-up was associated with 7–14% increase in ratings of worse subjective cognitive functioning over 3 months, relative to stable cognitive functioning. A similar attenuated pattern of findings was observed for the GAD7.
A clear association exists between subjective cognitive functioning outcomes and changes in self-reported severity of affective symptoms in young people over the first 3 months of treatment. Understanding the timing and mechanisms of these associations is needed to tailor treatment.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Background: Buprenorphine/naloxone (bup/nal) is a partial opioid agonist/antagonist and recommended first line treatment for opioid use disorder (OUD). Emergency departments (EDs) are a key point of contact with the healthcare system for patients living with OUD. Aim Statement: We implemented a multi-disciplinary quality improvement project to screen patients for OUD, initiate bup/nal for eligible individuals, and provide rapid next business day walk-in referrals to addiction clinics in the community. Measures & Design: From May to September 2018, our team worked with three ED sites and three addiction clinics to pilot the program. Implementation involved alignment with regulatory requirements, physician education, coordination with pharmacy to ensure in-ED medication access, and nurse education. The project is supported by a full-time project manager, data analyst, operations leaders, physician champions, provincial pharmacy, and the Emergency Strategic Clinical Network leadership team. For our pilot, our evaluation objective was to determine the degree to which our initiation and referral pathway was being utilized. We used administrative data to track the number of patients given bup/nal in ED, their demographics and whether they continued to fill bup/nal prescriptions 30 days after their ED visit. Addiction clinics reported both the number of patients referred to them and the number of patients attending their referral. Evaluation/Results: Administrative data shows 568 opioid-related visits to ED pilot sites during the pilot phase. Bup/nal was given to 60 unique patients in the ED during 66 unique visits. There were 32 (53%) male patients and 28 (47%) female patients. Median patient age was 34 (range: 21 to 79). ED visits where bup/nal was given had a median length of stay of 6 hours 57 minutes (IQR: 6 hours 20 minutes) and Canadian Triage Acuity Scores as follows: Level 1 – 1 (2%), Level 2 – 21 (32%), Level 3 – 32 (48%), Level 4 – 11 (17%), Level 5 – 1 (2%). 51 (77%) of these visits led to discharge. 24 (47%) discharged patients given bup/nal in ED continued to fill bup/nal prescriptions 30 days after their index ED visit. EDs also referred 37 patients with OUD to the 3 community clinics, and 16 of those individuals (43%) attended their first follow-up appointment. Discussion/Impact: Our pilot project demonstrates that with dedicated resources and broad institutional support, ED patients with OUD can be appropriately initiated on bup/nal and referred to community care.
Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.
Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.
All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).
The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.
The last 12 years have seen the evolution of a new funding regime under the supervision of the Pensions Regulator. Over this period, there has been significant turbulence in financial markets, including record low interest rates. This paper takes a critical look at the development of funding approaches and methodologies over this period. It analyses the Pensions Regulator guidance and how scheme specific actuarial methods have emerged since the move away from the Minimum Funding Requirement in 2001 and the introduction of the Scheme Specific Funding Requirements in 2005. It asks whether these new methodologies have been successful from the perspective of members, trustees, employers and shareholders. At a time when actuarial valuation methodologies have faced considerable criticism, this paper aims to propose a pension funding methodology which is fit for purpose and also reflects the latest guidance from the Pensions Regulator on integrated risk management.
Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8–24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43–4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61–2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.
We revise the data fitting in our original paper [The dissolution rates of simulated UK Magnox - ThORP blend nuclear waste glass as a function of pH, temperature and waste loading, Miner. Mag.79 (2015) 1529–1542]. The intrinsic rate constant data were calculated incorrectly, the corrected data are presented herein. To support the corrected analysis we have also taken the opportunity to report some additional 90°C data. The conclusions of the original paper remain sound.
The experiences of and reflections on interpersonal violence and victimisation among adolescents living in low- and middle-income countries are poorly understood. The aim was to describe Vietnamese adolescents’ reflections on their experiences of victimisation.
A self-completed, cross-sectional survey investigating exposure to violence among high school students in Hanoi, Vietnam was conducted during 2013–2014. The last section invited participants to write about any of the matters covered in the questionnaire. Thematic analysis was conducted on these free-text comments.
A total of 73/76 eligible students participated in the pilot and 1616/1745 in the main survey. Of these, a total of 239 records with free-text comments were analysed. Students described experiences of violence occurring at home, at school and in the community. Experiences of violence led to sadness, loneliness, having extremely negative thoughts about the value of life, and suicidal ideas. Adolescents’ experiences occurred in the context of poor parent–adolescent and teacher–student relationships, particularly concerning dissatisfaction with academic performance. Adolescents wanted to be trusted, to be given more autonomy, and to improve their relationships with parents and teachers.
Vietnamese adolescents experience various forms of victimisation, which are detrimental to their health and wellbeing. Understanding of their experiences of and perceptions of violence and its impact on their health and wellbeing is important in the prevention of violence against young people in Vietnam.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Objectives: Treatments for childhood brain tumors (BT) confer substantial risks to neurological development and contribute to neuropsychological deficits in young adulthood. Evidence suggests that individuals who experience more significant neurological insult may lack insight into their neurocognitive limitations. The present study compared survivor, mother, and performance-based estimates of executive functioning (EF), and their associations with treatment intensity history in a subsample of young adult survivors of childhood BTs. Methods: Thirty-four survivors (52.9% female), aged 18 to 30 years (M=23.5; SD=3.4), 16.1 years post-diagnosis (SD=5.9), were administered self-report and performance-based EF measures. Mothers also rated survivor EF skills. Survivors were classified by treatment intensity history into Minimal, Average/Moderate, or Intensive/Most-Intensive groups. Discrepancies among survivor, mother, and performance-based EF estimates were compared. Results: Survivor-reported and performance-based measures were not correlated, although significant associations were found between mother-reported and performance measures. Survivors in the Intensive/Most-Intensive treatment group evidenced the greatest score discrepancies, reporting less executive dysfunction relative to mother-reported F(2,31)=7.81, p<.01, and performance-based measures F(14,50)=2.54, p<.05. Conversely, survivors in the Minimal treatment group reported greater EF difficulties relative to mothers t(8)=2.82, p<.05, but not performance-based estimates (ps>.05). Conclusions: There may be a lack of agreement among survivor, mother, and performance-based estimates of EF skills in young adult survivors of childhood BT, and these discrepancies may be associated with treatment intensity history. Neuropsychologists should use a multi-method, multi-reporter approach to assessment of EF in this population. Providers also should be aware of these discrepancies as they may be a barrier to intervention efforts. (JINS, 2016, 22, 900–910)
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
This study investigated the incidence and risk to staff groups for sustaining needlestick injuries (NSIs) in the National University Hospital (NUH), Singapore. A retrospective cohort review of incident NSI cases was undertaken to determine the injury rate, causation, and epidemiological profile of such injuries. Analysis of the risk of sustaining recurrent NSI by occupation and location was done using the Cox proportional hazards model. There were 244 NSI cases in 5957 employees in NUH in 2014, giving an incidence rate of 4·1/100 healthcare workers (HCWs) per year. The incidence rate was highest for doctors at 21·3, and 2·7 for nurses; 40·6% of injuries occurred in wards, and 32·8% in operating theatres. There were 27 cases of repeated NSI cases. The estimated cost due to NSIs in NUH ranged from US$ 109 800 to US$ 563 152 in 2014. We conclude that creating a workplace environment where top priority is given to prevention of NSIs in HCWs, is essential to address the high incidence of reported NSIs. The data collected will be of value to inform the design of prevention programmes to reduce further the risk of NSIs in HCWs.