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Neuroimaging studies have documented brain structural changes in schizophrenia at different stages of the illness, including clinical high-risk (cHR), genetic high-risk (gHR), first-episode schizophrenia (FES), and chronic schizophrenia (ChS). There is growing awareness that neuropathological processes associated with a disease fail to map to a specific brain region but do map to a specific brain network. We sought to investigate brain structural damage networks across different stages of schizophrenia.
Methods
We initially identified gray matter alterations in 523 cHR, 855 gHR, 2162 FES, and 2640 ChS individuals relative to 6963 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to four specific networks.
Results
Brain structural damage networks of cHR and gHR had limited and non-overlapping spatial distributions, with the former mainly involving the frontoparietal network and the latter principally implicating the subcortical network, indicative of distinct neuropathological mechanisms underlying cHR and gHR. By contrast, brain structural damage networks of FES and ChS manifested as similar patterns of widespread brain areas predominantly involving the somatomotor, ventral attention, and subcortical networks, suggesting an emergence of more prominent brain structural abnormalities with illness onset that have trait-like stability over time.
Conclusions
Our findings may not only provide a refined picture of schizophrenia neuropathology from a network perspective, but also potentially contribute to more targeted and effective intervention strategies for individuals at different schizophrenia stages.
Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.
Chapter 16 discusses self-harm and suicidal thoughts in children and young people. We look at different ways children and young people may self-harm and the function of self-harm and how to offer support around it. We also consider how to support children expressing suicidal thoughts and discuss how to assess their level of risk and access appropriate help.
Adult daughters concerned about getting breast cancer throughout their lives and required support because their mothers had breast cancer.
Objectives
This article aims to examine the revised Information and Support Needs Questionnaire (ISNQ) and validate it in a Taiwanese community population comprising daughters of mothers with breast cancer.
Methods
Using convenience sampling, daughters of mothers with breast cancer were recruited and were separated into 2 samples (Sample 1, n = 102, and Sample 2, n = 118). First, we translated and modified the ISNQ to ensure cultural adaptation and formed ISNQ Chinese version (ISNQ-C). Second, we conducted an exploratory factor analysis using both samples to explore the ISNQ-C factor structure. Finally, we tested the criterion validity and known‐group validity of the ISNQ-C using Sample 2.
Results
Thirty-two items addressing 5 factors were identified for the ISNQ‐C. Each factor had good internal consistency. The criterion validity was supported by significant correlations between the ISNQ‐C scores and scores on the impacts of an event, anxiety, and depression. Known‐group comparisons revealed that the group with deceased mothers reported significantly more unmet needs related to “releasing my anxiety” compared to the group where the mother was stable and undergoing regular follow-ups.
Significance of results
The ISNQ‐C demonstrated good reliability and validity in terms of assessing needs among daughters of mothers with breast cancer in Taiwan. Using this assessment tool before genetic counseling to target the individual needs of this population at risk for breast cancer would be helpful to provide personalized care.
Dedicated on-site medical services have long been recommended to improve health outcomes at mass-gathering events (MGEs). In many countries, they are being reviewed as a mandatory requirement. While it is known that perceptions of risk shape substance use plans amongst outdoor music festival (OMF) attendees, it is unclear if attendees perceive the presence of on-site medical services as a part of the safety net. The aim of this paper is to better understand whether attendees’ perceptions of on-site medical services influence high-risk behaviors like alcohol and recreational drug use at OMFs.
Method:
A questionnaire was distributed to a random sample of attendees entering and attending two separate 20,000-person OMFs; one in Canada (Festival A) and one in New Zealand (Festival B). Responses focused on demographics, planned alcohol and recreational drug use, perceptions of medical services, and whether the absence of medical services would impact attendees’ planned substance use.
Results:
A total of 851 (587 and 264 attendees for Festival A and Festival B, respectively) attendees consented and participated. Gender distribution was equal and average ages were 23 to 25. At Festival A, 48% and 89% planned to use alcohol and recreational drugs, respectively, whereas at Festival B, it was 92% and 44%. A great majority were aware and supportive of the presence of medical services at both festivals, and a moderate number considered them a factor in attendance and something they would not attend without. There was significant (>10%) agreement (range 11%-46%; or 2,200-9,200 attendees for a 20,000-person festival) at both festivals that the absence of medical services would affect attendees’ planned use of alcohol and recreational drugs.
Conclusions:
This study found that attendees surveyed at two geographically and musically distinct OMFs had high but differing rates of planned alcohol and recreational drug use, and that the presence of on-site medical services may impact attendees’ perceptions of substance use risk. Future research will aim to address the limitations of this study to clarify these findings and their implications.
On p. 10 of the 2018 National Academies Exoplanet Science Strategy document (NASEM 2018), ‘Expect the unexpected’ is described as a general principle of the exoplanet field. But for the next 150 pages, this principle is apparently forgotten, as strategy decisions are repeatedly put forward based on our expectations. This paper explores what exactly it might mean to ‘expect the unexpected’, and how this could possibly be achieved by the space science community. An analogy with financial investment strategies is considered, where a balanced portfolio of low/medium/high-risk investments is recommended. Whilst this kind of strategy would certainly be advisable in many scientific contexts (past and present), in certain contexts – especially exploratory science – a significant disanalogy needs to be factored in: financial investors cannot choose low-risk high-reward investments, but sometimes scientists can. The existence of low-risk high-impact projects in cutting-edge space science significantly reduces the warrant for investing in high-risk projects, at least in the short term. However, high-risk proposals need to be fairly judged alongside medium- and low-risk proposals, factoring in both the degree of possible reward and the expected cost of the project. Attitudes towards high-risk high-impact projects within NASA since 2009 are critically analysed.
Before discussing the barriers to bringing claims against TNCs in countries where they are incorporated or domiciled (“home countries”), or where they engage in significant business, it is first important to understand why victims cannot, and thus do not, bring claims against TNC affiliates in their own countries where the harm occurs – the host country. In an ideal world, all countries would have regulatory systems sufficient to prevent harm to individuals and communities, and judicial or judicial-like mechanisms to provide for a remedy in the event that businesses engage in tortious actions, whether directly or vicariously. Many wonder why the victims simply do not bring a claim in their own country and question whether bringing a case outside their country is appropriate. Even the US Supreme Court has suggested that victims of human rights abuses should simply bring the case in their home country.1 However, it is not so simple. Indeed, if the victims could bring a claim in their own country and obtain a remedy, it would be much easier for them given the difficulty in bringing a case abroad against a parent company, and they would typically prefer to do so.2 Yet, the sad reality is that this is often not possible in many host countries where TNCs operate. First, many of these host countries do not have sufficient regulations to prevent harm; in fact, as a result of globalization, many have done away with regulations in order to attract transnational business.
Pulmonary embolism (PE) is a potentially life-threatening condition. The management of low, intermediate and high-risk PE are explained in a stepwise fashion. Readers are provided with information on thrombolysis, and how to anticoagulate following this intervention.
Prevention of psychosis has become a major objective of modern clinical psychiatry. An increasing number of new services have been established in Europe and in the world. The OASIS team has become an established model where clinical practice and research are fully integrated in the field of preventative interventions in psychosis.
Method:
Comprehensive analysis of different clinical and service measures describing the 2001–2011 implementation of the OASIS team.
Results:
Over the last decade, the OASIS team has received a total of 1102 referrals, mostly young males from ethnic minorities. After the assessment, 35% were diagnosed with an At Risk Mental State (ARMS) while 32% were already psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic deterioration syndrome, 9% met inclusion criteria for a brief and self-limited intermittent psychotic episode and the others met inclusion criteria for more than one subgroup. Most of them had at least one comorbid diagnosis, mainly relating to anxiety and depressive domains. The majority of the OASIS clients received cognitive behavioural therapy alone or in combination with antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects (15.2%) developed a frank psychotic episode.
Conclusions:
The OASIS service represents one of the largest and most established prodromal services in the world. The burden of research evidence and the translational impact produced on the clinical practice support the OASIS as a model for the development of similar services.
Radiotherapy is one of the treatments used to treat prostate cancer, and dose escalation to 74–78 Gy in conventional fractionation is the standard regimen. Currently, according to the hypothesis of low alpha/beta ratio in prostate cancer cells, using hypo-fractionation has been reported in many publications with promising results. This retrospective study was designed to evaluate the implementation of a moderate hypo-fractionation regimen in high-risk prostate cancer in our division.
Materials and Methods:
Between 2012 and 2017, 40 patients with high-risk, localised prostate cancer were treated by a moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) with intensity-modulated radiation therapy. The data related to treatment outcomes and toxicities were evaluated.
Results:
The mean PSA at diagnosis was 86·2 ng/mL (95% CI 49·9–122·4). Thirty-eight patients received long-term hormonal therapy. Fifty-two percent had a Gleason score of 8–10, and 65% had an initial PSA >20 ng/mL. The mean doses (in EQD2) to the D50% of PTV, D2% of organs at risk (bladder, rectum and bowels) were 80, 78·3, 76·4, and 50·2 Gy, respectively. Two patients had biochemical recurrence during the follow-up period.
Conclusion:
A moderate hypo-fractionation regimen (70 Gy at 2·5 Gy per fraction) is feasible. Our experience found that this regimen yields tolerable, acceptable toxicity profiles in high-risk, localised prostate cancer patients.
Community-acquired pneumonia (CAP) results in substantial numbers of hospitalisations and deaths in older adults. There are known lifestyle and medical risk factors for pneumococcal disease but the magnitude of the additional risk is not well quantified in Australia. We used a large population-based prospective cohort study of older adults in the state of New South Wales (45 and Up Study) linked to cause-specific hospitalisations, disease notifications and death registrations from 2006 to 2015. We estimated the age-specific incidence of CAP hospitalisation (ICD-10 J12-18), invasive pneumococcal disease (IPD) notification and presumptive non-invasive pneumococcal CAP hospitalisation (J13 + J18.1, excluding IPD), comparing those with at least one risk factor to those with no risk factors. The hospitalised case-fatality rate (CFR) included deaths in a 30-day window after hospitalisation. Among 266 951 participants followed for 1 850 000 person-years there were 8747 first hospitalisations for CAP, 157 IPD notifications and 305 non-invasive pneumococcal CAP hospitalisations. In persons 65–84 years, 54.7% had at least one identified risk factor, increasing to 57.0% in those ⩾85 years. The incidence of CAP hospitalisation in those ⩾65 years with at least one risk factor was twofold higher than in those without risk factors, 1091/100 000 (95% confidence interval (CI) 1060–1122) compared with 522/100 000 (95% CI 501–545) and IPD in equivalent groups was almost threefold higher (18.40/100 000 (95% CI 14.61–22.87) vs. 6.82/100 000 (95% CI 4.56–9.79)). The CFR increased with age but there were limited difference by risk status, except in those aged 45 to 64 years. Adults ⩾65 years with at least one risk factor have much higher rates of CAP and IPD suggesting that additional risk factor-based vaccination strategies may be cost-effective.
Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.
Aims
To examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability.
Method
Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS).
Results
The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54–1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3–9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6–50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97.
Conclusions
Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.
Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention.
Method
In total 287 participants aged 12–30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes.
Results
At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of ‘conversion’ to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania.
Conclusions
This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.
Following the loss of a loved one to cancer, a significant subset of bereaved family members are at heightened risk for mental and physical health problems; however, these family members often “fall through the cracks” of the healthcare system. A brief, clinically useful self-report bereavement risk-screening tool could facilitate more effective identification of family members in need of psychosocial support before and after a cancer loss. Thus, the purpose of this study was to develop and refine the Bereavement Risk Inventory and Screening Questionnaire (BRISQ), a self-report bereavement screening tool, and to assess its utility using feedback from bereavement experts.
Method:
Quantitative and qualitative feedback from a panel of 15 clinical and research experts in bereavement was obtained through an online survey to identify the most clinically useful items and understand expert opinion on bereavement screening.
Results:
The qualitative and quantitative feedback were synthesized, resulting in a 22% reduction of the item pool. While there was a general consensus between experts on the most clinically useful risk factors for bereavement-related mental health challenges and on the utility of screening, they also offered feedback on language and formatting that guided substantial revisions to the BRISQ.
Significance of results:
These findings were utilized to refine the BRISQ in preparation for a second study to obtain family member feedback on the measure. By incorporating both expert and family member feedback, the intention is to create a screening tool that represents top clinical and research knowledge in bereavement in a way that effectively addresses barriers to care.
The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown.
Method.
We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses.
Results.
The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive–compulsive disorder symptoms.
Conclusions.
Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.
Core social interaction behaviors were examined in young children 0–36 months of age who were hospitalized for accidental (n = 61) or inflicted (n = 64) traumatic brain injury (TBI) in comparison to typically developing children (n = 60). Responding to and initiating gaze and joint attention (JA) were evaluated during a semi-structured sequence of social interactions between the child and an examiner at 2 and 12 months after injury. The accidental TBI group established gaze less often and had an initial deficit initiating JA that resolved by the follow-up. Contrary to expectation, children with inflicted TBI did not have lower rates of social engagement than other groups. Responding to JA was more strongly related than initiating JA to measures of injury severity and to later cognitive and social outcomes. Compared to complicated-mild/moderate TBI, severe TBI in young children was associated with less responsiveness in social interactions and less favorable caregiver ratings of communication and social behavior. JA response, family resources, and group interacted to predict outcomes. Children with inflicted TBI who were less socially responsive and had lower levels of family resources had the least favorable outcomes. Low social responsiveness after TBI may be an early marker for later cognitive and adaptive behavior difficulties. (JINS, 2013, 19, 1–11)
The past two decades have seen exponential clinical and research interest in help-seeking individuals presenting with potentially prodromal symptoms for psychosis. However, the epidemiological validity of this paradigm has been neglected, limiting future advancements in the field.
Method
We undertook a critical review of core epidemiological issues underlying the clinical high-risk (HR) state for psychosis and which model of prodromal intervention is best suited for mental health.
Results
The HR state for psychosis model needs refining, to bring together population-based findings of high levels of psychotic experiences (PEs) and clinical expression of risk. Traditionally, outcome has been attributed to ‘HR criteria’ alone rather than taking into account sampling strategies. Furthermore, the exclusive focus on variably defined ‘transition’ obscures true variation in the slow and non-linear progression across stages of psychopathology. Finally, the outcome from HR states is variable, indicating that the underlying paradigm of ‘schizophrenia light progressing to schizophrenia’ is inadequate.
Conclusions
In the general population, mixed and non-specific expression of psychosis, depression, anxiety and subthreshold mania is common and mostly transitory. When combined with distress, it may be considered as the first, diagnostically neutral stage of potentially more severe psychopathology, which only later may acquire a degree of diagnostic specificity and possible relative resistance to treatment. Therefore, rather than creating silos of per-disorder ultra-HR syndromes, an early intervention focus on the broad syndrome of early mental distress, requiring phase-specific interventions, may be more profitable.
Although it is well established that cognitive impairment is a common feature of schizophrenia, only recently has cognitive functioning been prospectively studied in individuals at clinical high risk (CHR) for developing psychosis. To date, both cross-sectional and longitudinal studies have been conducted in the CHR population and in the context of later conversion to psychosis. A comprehensive review of the literature suggests that CHR individuals have general and specific baseline cognitive deficits compared to healthy controls. As a group, their cognitive course, tends to remain stable over time and in this way does not differ from healthy controls. For those who go on to develop a full-blown psychotic illness compared to those who do not convert, there appeared to be minimal differences at baseline with respect to cognition, although over time the converters may show deterioration in certain cognitive abilities compared to the non-converters. However, for many cognitive domains results are mixed, and may result from methodological limitations.
Increased sensitivity and exposure to stress are associated with psychotic symptoms in schizophrenia and its risk states, but little is known about the co-evolution of stress sensitivity and exposure with positive and other symptoms in a clinical high-risk (CHR) cohort.
Method
A combined cross-sectional and longitudinal design was used to examine the associations over time of stress sensitivity and exposure (i.e. life events) with ‘prodromal’ symptoms in a cohort of 65 CHR patients assessed quarterly for up to 4 years, and at baseline in 24 healthy controls similar in age and gender.
Results
Impaired stress tolerance was greater in patients, in whom it was associated over time with positive and negative symptoms, in addition to depression, anxiety and poor function. By contrast, life events were comparable in patients and controls, and bore no association with symptoms. In this treated cohort, there was a trajectory of improvement in stress tolerance, symptoms and function over time.
Conclusions
Impaired stress tolerance was associated with a wide range of ‘prodromal’ symptoms, consistent with it being a core feature of the psychosis risk state. Self-reported life events were not relevant as a correlate of clinical status. As in other treated CHR cohorts, most patients improved over time across symptom domains.
Clinical and epidemiological studies suggest an association between cannabis use and psychosis but this relationship remains controversial.
Method
Clinical high-risk (CHR) subjects (age 12–22 years) with attenuated positive symptoms of psychosis (CHR+, n=101) were compared to healthy controls (HC, n=59) on rates of substance use, including cannabis. CHR+ subjects with and without lifetime cannabis use (and abuse) were compared on prodromal symptoms and social/role functioning at baseline. Participants were followed an average of 2.97 years to determine psychosis conversion status and functional outcome.
Results
At baseline, CHR+ subjects had significantly higher rates of lifetime cannabis use than HC. CHR+ lifetime cannabis users (n=35) were older (p=0.015, trend), more likely to be Caucasian (p=0.002), less socially anhedonic (p<0.001) and had higher Global Functioning: Social (GF:Social) scores (p<0.001) than non-users (n=61). CHR+ cannabis users continued to have higher social functioning than non-users at follow-up (p<0.001) but showed no differences in role functioning. A small sample of CHR+ cannabis abusers (n=10) showed similar results in that abusers were older (p=0.008), less socially anhedonic (p=0.017, trend) and had higher baseline GF:Social scores (p=0.006) than non-abusers. Logistic regression analyses revealed that conversion to psychosis in CHR+ subjects (n=15) was not related to lifetime cannabis use or abuse.
Conclusions
The current data do not indicate that low to moderate lifetime cannabis use is a major contributor to psychosis or poor social and role functioning in clinical high-risk youth with attenuated positive symptoms of psychosis.