This paper provides new insights into the effect of birth cohort size on cohort lifetime wages and its sensitivity to the future trajectories of immigration and fertility. The main innovation is to relax the typical assumption of perfect substitution of labor by age. The effect of imperfect substitution of labor by age is to qualify the standard result that smaller birth cohorts are likely to enjoy relatively high wages since that result depends on the size of co-worker cohorts. The positive small cohort effect on lifetime wages therefore depends on demographic patterns, which are simulated here through low and high fertility and immigration projections. The analysis applies to actual and projected cohorts for Australia and tests the sensitivity to alternative demographic parameters, and the substitution and discount parameters. The effects of imperfect substitution can amount several percentage points of lifetime wages.

The Ross Sea is known for showing the greatest sea-ice increase, as observed globally, particularly from 1979 to 2015. However, corresponding changes in sea-ice thickness and production in the Ross Sea are not known, nor how these changes have impacted water masses, carbon fluxes, biogeochemical processes and availability of micronutrients. The PIPERS project sought to address these questions during an autumn ship campaign in 2017 and two spring airborne campaigns in 2016 and 2017. PIPERS used a multidisciplinary approach of manned and autonomous platforms to study the coupled air/ice/ocean/biogeochemical interactions during autumn and related those to spring conditions. Unexpectedly, the Ross Sea experienced record low sea ice in spring 2016 and autumn 2017. The delayed ice advance in 2017 contributed to (1) increased ice production and export in coastal polynyas, (2) thinner snow and ice cover in the central pack, (3) lower sea-ice Chl-a burdens and differences in sympagic communities, (4) sustained ocean heat flux delaying ice thickening and (5) a melting, anomalously southward ice edge persisting into winter. Despite these impacts, airborne observations in spring 2017 suggest that winter ice production over the continental shelf was likely not anomalous.

This study estimated the cost-effectiveness of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in Austria, as well as the costs related to the discontinuation of antidepressant treatment from the perspective of the Austrian Sick Funds (Gebietskrankenkassen).

The economic analyses were based on a meta-analysis of four randomised clinical trials comparing mirtazapine with amitriptyline, and on a six week comparative trial of mirtazapine and fluoxetine which was extrapolated to six months using assumptions derived from the literature. Decision models of the treatment paths and associated resource use attributable to managing moderate and severe depression in Austria were developed from clinical trial data, information on Austrian clinical practice obtained from interviews with an Austrian Delphi panel (comprising psychiatrists and GPs), and from published literature. The models were used to estimate the expected costs to the Gebietskrankenkassen of managing a patient with moderate or severe depression, and the indirect cost per patient to Austrian society due to lost productivity.

The expected cost to the Gebietskrankenkassen of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment was estimated to be ATS 4,088 over five months, of which hospitalisations accounted for nearly 69% of the cost.

Using mirtazapine instead of amitriptyline for 28 weeks increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%), and reduces the expected cost to the Gebietskrankenkassen by ATS 1,112 per patient (from ATS 31,411 to ATS 30,299). Patients treated with mirtazapine and amitriptyline for 28 weeks are expected to miss 4.76 and 5.01 weeks of work respectively, due to their depression. Hence, the expected indirect cost to Austrian society over this period was estimated to be ATS 58,787 and ATS 61,851 per patient respectively.

Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for a negligible additional cost to the Gebietskrankenkassen of ATS 408 per patient (from ATS 29,205 to ATS 29,613). Patients treated with mirtazapine and fluoxetine for six months are expected to miss 4.53 weeks of work, due to their depression. Hence, the expected indirect cost to Austrian society due to lost productivity was estimated to be ATS 55,900 per patient with either antidepressant.

In conclusion, this study suggests that despite the differences in acquisition costs, mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine, supporting the adoption of this treatment in the management of moderate and severe depression in Austria.

This study modelled the economic impact of mirtazapine, compared to amitriptyline and fluoxetine, in the management of moderate and severe depression in the UK, as well as the costs related to discontinuation of antidepressant treatment.

Decision models of the management of moderate and severe depression were developed from clinical trial data, resource use obtained from interviews with general practitioners and psychiatrists, and published literature, and were used to estimate the expected direct National Health Service (NHS) costs of managing a patient with moderate or severe depression.

The expected cost of healthcare resource use attributable to managing a patient suffering from moderate or severe depression who discontinues antidepressant treatment, irrespective of the initial treatment, was estimated to be £206 (range £50 to £504) over five months.

Using mirtazapine instead of amitriptyline for seven months increases the proportion of successfully treated patients by 21% (from 19.2 to 23.2%) and reduces the expected direct NHS cost by £35 per patient (from £448 to £413). Using mirtazapine instead of fluoxetine for six months increases the proportion of successfully treated patients by 22% (from 15.6 to 19.1%), albeit for an additional cost to the NHS of £27 per patient (from £394 to £420).

In conclusion, this study suggests that mirtazapine is a cost-effective antidepressant compared to amitriptyline and fluoxetine in the management of moderate and severe depression in the UK.

In schizophrenia, sex differences related to age of onset, course of illness and response to antipsychotic treatment may be mirrored by differences in the underlying molecular pathways. We attempted to increase our understanding of these phenomena by carrying out multiplex immunoassay profiling of 95 serum molecules using samples from 4 independent cohorts of male and female first episode antipsychotic naive schizophrenia patients (n=133) and matched controls (n=133). The concentrations of 16 molecules associated with hormonal, inflammation and growth factor pathways showed significant sex differences in schizophrenia patients compared with controls. In line with the numerous sex differences reported in schizophrenia, our findings included alterations in the levels of several hormones, including elevated free and total testosterone in female patients and concomitant sex differences in sex hormone binding globulin and prolactin concentrations. We also found higher levels of thyroxine binding globulin and seven inflammatory markers in male schizophrenia patients only, raising the possibility that some aspects of the widely-reported immunological abnormalities in schizophrenia may be specific for males. Several of these markers showed sexspecific associations with positive and negative syndrome scale (PANSS) scores and changes in concentration after 6 weeks of treatment with antipsychotics. Finally, we also evaluated overlapping and distinct sex-specific biomarkers for schizophrenia, Asperger syndrome, major depressive disorder and bipolar disorder. We propose that future studies should investigate the common and sex-specific aetiologies of schizophrenia, as the current findings suggest that different therapeutic strategies may be required for male and female patients.

This article examines two intertwined topics on architected materials with imperfections—their mechanics and optimum design. We first discuss the main factors that control defect sensitivity along with a range of strategies for defect characterization. The potency of both as-designed and as-manufactured defects on their macroscopic response is highlighted with an emphasis on those caused by additive manufacturing technology. As a natural extension of defect sensitivity, we describe the design approaches for architected materials with particular focus on systematic tools of topology optimization. Recent extensions to formally incorporate imperfections in the optimization formulation are discussed, where the ultimate goal is to generate architectures that are flaw-tolerant and perform robustly in the presence of imperfections. We conclude with an outlook on the field, highlighting potential areas of future research.

Bio-Detection Dogs (BDDs) are used in some high-income countries as a diagnostic intervention, yet little is known about their potential in low/middle-income countries with limited diagnostic resources. This exploratory study investigated the opportunities and implications of deploying BDDs as a mobile diagnostic intervention to identify people with asymptomatic malaria, particularly at ports of entry, as an important step to malaria elimination in a population. A qualitative study design consisting of participant observation, five focus group discussions and informal conversations was employed in The Gambia in April–May 2017. A disciplined German Shepherd companion dog (not trained as a BDD) was introduced to research participants and their perceptions recorded. Field-notes and discussions were transcribed, translated and analysed thematically. Most research participants viewed positively the possibility of using BDDs to detect malaria, with the major advantage of being non-invasive. Some concerns, however, were raised regarding safety and efficacy, as well as cultural issues around the place of dogs within human society. The Gambia is a rabies-endemic country, and unfamiliar dogs are not usually approached, with implications for how research participants perceived BDDs. Understanding such concerns and working with local people to address such issues must be part of any successful strategy to deploy BDDs in new settings. Bio-Detection Dogs represent a potentially non-invasive diagnostic tool for the detection of asymptomatic or chronic malaria infections, particularly in areas with very low parasite rates. However, it is important to understand local concerns and work closely with communities to address those concerns. Wider deployment of BDDs will also require careful planning and sustained financial support.