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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To describe characteristics of self-identified popular diet followers and compare mean BMI across these diets, stratified by time following diet.
Cross-sectional, web-based survey administered in 2015.
Non-localised, international survey.
Self-selected followers of popular diets (n 9019) were recruited to the survey via social media and email announcements by diet community leaders, categorised into eight major diet groups.
General linear models were used to compare mean BMI among (1) short-term (<1 year) and long-term (≥1 year) followers within diet groups and (2) those identifying as ‘try to eat healthy’ (TTEH) to all other diet groups, stratified by time following the specific diet. Participants were 82 % female, 93 % White and 96 % non-Hispanic. Geometric mean BMI was lower (P < 0·05 for all) among longer-term followers (≥1 year) of whole food, plant-based (WFPB), vegan, whole food and low-carb diets compared with shorter-term followers. Among those following their diet for 1–5 years (n 4067), geometric mean BMI (kg/m2) were lower (P < 0·05 for all) for all groups compared with TTEH (26·4 kg/m2): WFPB (23·2 kg/m2), vegan (23·5 kg/m2), Paleo (24·6 kg/m2), vegetarian (25·0 kg/m2), whole food (24·6 kg/m2), Weston A. Price (23·5 kg/m2) and low-carb (24·7 kg/m2).
Our findings suggest that BMI is lower among individuals who made active decisions to adhere to a specific diet, particularly more plant-based diets and/or diets limiting highly processed foods, compared with those who simply TTEH. BMI is also lower among individuals who follow intentional eating plans for longer time periods.
The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.
Higher all-cause mortality and shorter life expectancies for people with severe mental illness (SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder) have been frequently reported. Cancer contributes a substantial proportion of mortality (20 to 30%) as the second or third leading cause of death among people with SMI. Outcomes of cancer incidence studies in SMI were considerably heterogeneous, varying by cancer types and mental disorders.
To compare the incidence of overall and each type of cancer between people with SMI in southeast London and general population in UK.
Using the anonymised linkage between a regional monopoly secondary mental health service provider covering four southeast London boroughs and a population-based cancer register, we carried out the comparisons of cancer incidences between people with SMI and general population by age- and gender-standardisation in 2011.
Among SMI subjects with cancer (N=105), the most common cancer types were lung and colorectal cancer followed by breast cancer for women and prostate cancer for men in this area. Standardised incidence ratios (SIRs) for all cancers in SMI were 1.19 (95% CI: 0.97-1.44) overall, 2.43 (95% CI: 1.98-2.94) in men (n=61), and 0.98 (95% CI: 0.71-1.31) in women (n=44). Based on relatively small case numbers, raised SIRs were found for lung cancer in men (SIR=7.57, 95% CI: 3.04-15.6) and women (SIR=7.61, 95% CI: 2.79-16.6), and in women for colorectal (SIR=7.85, 95%CI: 2.55-18.32) and breast cancer (SIR=7.86, 95% CI: 4.58-12.59).
Specific pattern of elevated risks of cancer incidence were found for people with SMI.
With the widespread of atypical antipsychotics used among children and adolescents, the treatment effectiveness has been of great interest alongside with the efficacy and safety in this population. The study was designed to assess whether second-generation antipsychotics (SGAs) are associated with lower service costs in the real world. Factors associated with service costs were also examined.
The claim data (PIMC) of 1996-2008 from the National Insurance Plan of Taiwan was used. Patients aged less than 20 with an incident use of antipsychotics and last for 12 months during this period were included for analysis. Comparisons were made between 8 SGAs and 2 first-generation antipsychotics (FGAs). Changes in service costs were examined with 95% confidence interval. Multivariate regressions with propensity scores adjustment were performed to explore factors associated with psychiatric service costs.
A total of 343 treatment encounters were included and results showed no difference in psychiatric services costs in the SGAs group as the total service costs were offset to high antipsychotics costs of SGAs, though antiparkinsonian costs were not different between two groups. Factor positively associated with service costs were relapse (RR=4.0, p< 0.0001) and EPS incidence (RR=1.6, p< 0.008), while types of antipsychotics and diagnoses were not significant factors after adjusting for covariates.
Service costs were not different between FGAs and SGAs groups and medication costs were significantly higher in the SGAs group. Relapse and EPS incidence were factors of high costs among children and adolescents psychiatric patients treated with antipsychotics in Taiwan.
The life expectancy gap between people with severe mental illness (SMI) and the general population persists and may even be widening. This study aimed to estimate contributions of specific causes of death to the gap. Age of death and primary cause of death were used to estimate life expectancy at birth for people with SMI from a large mental healthcare case register during 2007–2012. Using data for England and Wales in 2010, death rates in the SMI cohort for each primary cause of death category were replaced with gender- and age-specific norms for that cause. Life expectancy in SMI was then re-calculated and, thus, the contribution of that specific cause of death estimated. Natural causes accounted for 79.2% of lost life-years in women with SMI and 78.6% in men. Deaths from circulatory disorders accounted for more life-years lost in women than men (22.0% versus 17.4%, respectively), as did deaths from cancer (8.1% versus 0%), but the contribution from respiratory disorders was lower in women than men (13.7% versus 16.5%). For women, cancer contributed more in those with non-affective than affective disorders, while suicide, respiratory and digestive disorders contributed more in those with affective disorders. In men, respiratory disorders contributed more in non-affective disorders. Other contributions were similar between gender and affective/non-affective groups. Loss of life expectancy in people with SMI is accounted for by a broad range of causes of death, varying by gender and diagnosis. Interventions focused on multiple rather than individual causes of death should be prioritised accordingly.
Types of sugar-sweetened beverages (SSB) can differ greatly between countries, with greater consumption of sweetened tea in Asia. This study aimed to understand changes in SSB consumption by adolescents in Taiwan over 18 years and their association with demographic characteristics and clinical outcome. This study used survey data from the 1993–1996 and 2010–2011 Nutrition and Health Surveys in Taiwan. Participants were high school students aged 13 to 18 years. Data were weighted and analysed using SUDAAN 11.0 and SAS 9.4. Participants were asked about intake frequencies of SSB and were grouped into four different SSB intake groups based on the combination of high or low frequency (including moderate frequency) of intake of sweetened tea and soda/sports/energy drinks. Results indicated over 99 % of teens reported having at least one SSB in the past week. Smoking status was significantly associated with SSB intake types with high tea intake (high tea and low soda (HL) group, OR 7·56, P < 0·001; high tea and high soda (HH) group, OR 9·96, P < 0·001). After adjustment for potential confounders, adolescents in the low tea and high soda (LH) group (β = 0·05, P = 0·034) had significantly higher mean serum uric acid values. In conclusion, sugary tea remains the SSB of choice for Taiwanese adolescents. Those with a frequent intake of soda/sports/energy drinks had a higher chance of being hyperuricaemic.
The influence of combined corrosion and vibration to the anti-loosening performance of a precision locknut used in a machine tool is investigated. Firstly, the locknut was submerged in 5% NaCl solution according to ASTM B895 standard for corrosion testing. The locknuts, after submerged in 1-hr, 2-hr and 4-hr periods, respectively, were then installed on the rotating spindle in a vertical dynamic impact tester for performing anti-loosening test. The initial installed pretension was 9800 N and the spindle was rotating in a constant speed of 1000 rpm. Turmogrease Li 802 EP lubricant was used on the contact surface between spindle thread and locknut. The set screws on the locknut were tightened sequentially and evenly in three-stage of torque: 1.96 N-m, 3.92 N-m and 5.88 N-m. Its real-time pretension variation with the periodic transverse impact and its final loosening torque were measured. Accordingly, the axial force ratio and anti-loosening torque ratio were calculated and discussed. It was found that corrosion treatment had similar influence on both the axial force ratio and the anti-loosening torque ratio. More corrosion on the locknut with longer submersion in NaCl solution deteriorated its anti-loosening characteristics. The result could serve as the reference for evaluating the fastening performance of precision locknut and guide the design and manufacturing for the application improvement.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.
Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.
Economically depressed small-town population.
Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).
Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).
Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
The second Singapore Mental Health Study (SMHS) – a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010.
Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010.
The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.
Borderline personality disorder (BPD) is characterized by a heterogeneous clinical phenotype that emerges from interactions among genetic, biological, neurodevelopmental, and psychosocial factors. In the present family study, we evaluated the familial aggregation of key clinical, personality, and neurodevelopmental phenotypes in probands with BPD (n = 103), first-degree biological relatives (n = 74; 43% without a history of psychiatric disorder), and non-psychiatric controls (n = 99).
Participants were assessed on DSM-IV psychiatric diagnoses, symptom dimensions of emotion dysregulation and impulsivity, ‘big five’ personality traits, and neurodevelopmental characteristics, as part of a larger family study on neurocognitive, biological, and genetic markers in BPD.
The most common psychiatric diagnoses in probands and relatives were major depression, substance use disorders, post-traumatic stress disorder, anxiety disorders, and avoidant personality disorder. There was evidence of familial aggregation for specific dimensions of impulsivity and emotion dysregulation, and the big five traits neuroticism and conscientiousness. Both probands and relatives reported an elevated neurodevelopmental history of attentional and behavioral difficulties.
These results support the validity of negative affectivity- and impulse-spectrum phenotypes associated with BPD and its familial risk. Further research is needed to investigate the aggregation of neurocognitive, neural and genetic factors in families with BPD and their associations with core phenotypes underlying the disorder.
Evidence suggests that semantic interference may be a sensitive indicator of early dementia. We examined the utility of the Semantic Interference Test (SIT), a cognitive stress memory paradigm which taps proactive and retroactive semantic interference, for predicting progression from mild cognitive impairment (MCI) to dementia in both a clinical and a population-based sample.
Participants with MCI in the clinical (n = 184) and population-based (n = 435) samples were followed for up to four years. We employed receiver operating characteristic (ROC) methods to establish optimal thresholds for four different SIT indices. Threshold performance was compared in the two samples using logistic and Cox proportional hazard regression models.
Within four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%) individuals in the population-based sample progressed to dementia. Overall classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different subtests of the SIT had slightly different performance characteristics in the two samples. However, regression models showed that thresholds established in the clinical sample performed similarly in the population sample before and after adjusting for demographics and other baseline neuropsychological test scores.
Despite differences in demographic composition and progression rates, baseline SIT scores predicted progression from MCI to dementia similarly in both samples. Thresholds that best predicted progression were slightly below thresholds established for distinguishing between amnestic MCI and cognitively normal subjects in clinical practice. This confirms the utility of the SIT in both clinical and population-based samples and establishes thresholds most predictive of progression of individuals with MCI.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
This study presents a new groove profile using the slant groove depth arrangements to enhance the performance of micro-HGJBs. The computational analysis was based on the steady-state three-dimensional conservation equations of mass and momentum in conjunction with the cavitation model to examine the complex lubricated flow field. The simulated results of load capacity and circumferential pressure distribution of lubricant film are in good agreement with the measurement data and the predictions cited in the literature. Numerical experiments were extended to determine the pressure distribution, load capacity, radial stiffness and friction torque by varying the slant ratio of groove depth, eccentricity ratio, rotational speed and attitude angle. The cavitation extent of lubricant film was also studied for different slant groove patterns.
Detrimental effects of ultraviolet (UV) light on living organisms are well understood, little is known about the effects of blue light irradiation. Although a recent study revealed that blue light caused more harmful effects on insects than UV light and blue light irradiation killed insect pests of various orders including Diptera, the effects of blue light on physiology of insects are still largely unknown. Here we studied the effects of blue light irradiation on cuticular melanin in larval and the immune response in adult stage of Bactrocera dorsalis. We also evaluated the effects of blue light exposure in larval stage on various age and mass at metamorphosis and the mediatory role of cuticular melanin in carryover effects of larval stressors across metamorphosis. We found that larvae exposed to blue light decreased melanin contents in their exoskeleton with smaller mass and delayed metamorphosis than insects reared without blue light exposure. Across metamorphosis, lower melanotic encapsulation response and higher susceptibility to Beauveria bassiana was detected in adults that had been exposed to blue light at their larval stage, thereby constituting the first evidence that blue light impaired adult immune function in B. dorsalis as a carryover effect of larval exposure.
Given the concerns regarding the adverse health outcomes associated with weight gain and metabolic syndrome in relation to use of second-generation antipsychotics (SGAs), we aimed in this study to explore whether the increase in the use of SGAs would have any impacts on the trend of excess mortality in people with schizophrenia and bipolar disorder (BPD).
Two nationwide samples of individuals with schizophrenia and BPD were identified in Taiwan's National Health Insurance Research Database in 2003 and in 2008, respectively. Age- and gender-standardized mortality ratios (SMRs) were calculated for each of the 3-year observation periods. The SMRs were compared between the calendar year cohorts, by disease group, and by causes of death.
The mortality gap for people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI 3.30–3.50) for the 2003 cohort and 3.14 (3.06–3.23) for the 2008 cohort. The mortality gap for BPD individuals remained relatively stable with only those aged 15–44 years having an SMR rising significantly from 7.04 (6.38–7.76) to 9.10 (8.44–9.79). Additionally, in this group of BPD patients aged 15–44 years, the natural-cause-SMR increased from 5.65 (4.93–6.44) to 7.16 (6.46–7.91).
Compared with the general population, the gap in the excess mortality for people with schizophrenia reduced slightly. However, the over 200% difference between the cohorts in the excess mortality for BPD individuals aged 15–44 years could be a warning sign. Future research to further examine the related factors underlying those changes is warranted.