The impact of depression, anxiety and comorbidity on occupational outcomes.

BACKGROUND: Anxiety and depression account for considerable cost to organizations, driven by both presenteeism (reduced performance due to attending work while ill) and absenteeism. Most research has focused on the impact of depression, with less attention given to anxiety and comorbid presentations. AIMS: To explore the cross-sectional relationship between depression and anxiety (individually and comorbidly) on workplace performance and sickness absence. METHODS: As part of a larger study to evaluate a mental health app, 4953 working Australians were recruited. Participants completed in-app assessment including demographic questions, the Patient Health Questionnaire-9, two-item Generalized Anxiety Disorder and questions from the World Health Organization Health and Work Performance Questionnaire. Cut-off scores were used to establish probable cases of depression alone, anxiety alone and comorbidity. RESULTS: Of the total sample, 7% met cut-off for depression only, 13% anxiety only, while 16% were comorbid. Those with comorbidity reported greater symptom severity, poorer work performance and more sickness absence compared to all other groups. Presenteeism and absenteeism were significantly worse in those with depression only and anxiety only compared to those with non-clinical symptom levels. Although those with depression alone tended to have poorer outcomes than the anxiety-only group, when sample prevalence rates were considered, the impact on presenteeism was comparable. CONCLUSIONS: Workplace functioning is heavily impacted by depression and anxiety both independently and where they co-occur. While comorbidity and more severe depression presentations stand out as impairing, workplace interventions should also prioritize targeting of anxiety disorders (and associated presenteeism) given their high population prevalence.

Human placental villi contain stromal macrovesicles associated with networks of stellate cells.

Placental function is essential for fetal development and establishing the foundations for lifelong health. The placental villous stroma is a connective tissue layer that supports the fetal capillaries and villous trophoblast. All the nutrients that cross the placenta must also cross the stroma, and yet little is known about this region. This study uses high-resolution three-dimensional imaging to explore the structural complexity of this region within the placental villi. Serial block-face scanning electron microscopy and confocal microscopy were used to image the placental villous stroma in three-dimensions. Transmission electron microscopy (TEM) was used to generate high resolution two-dimensional images. Stereological approaches were used to quantify volumes of stromal constituents. Three-dimensional imaging identified stromal extracellular vesicles, which constituted 3.9% of the villous stromal volume. These stromal extracellular vesicles were ovoid in shape, had a median length of 2750 nm (range 350-7730 nm) and TEM imaging confirmed that they were bounded by a lipid bilayer. Fifty-nine per cent of extracellular vesicles were in contact with a fibroblast-like stellate cell and these vesicles were significantly larger than those where no contact was observed. These stellate cells formed local networks with adherent junctions observed at contact points. This study demonstrates that the villous stroma contains extracellular macrovesicles which are considerably larger than any previously described in tissue or plasma. The size and abundance of these macrovesicles in the villous stroma highlight the diversity of extracellular vesicle biology and their roles within connective tissues.

The relationship between depression symptoms, absenteeism and presenteeism.

BACKGROUND: Mental health problems are common within the working population. Depression is both highly prevalent and debilitating and is linked to increases in absenteeism and presenteeism. The use of summed depression scale scores may conceal differential impacts of depressive symptoms on absenteeism and presenteeism. We aimed to explore both the relationship between absenteeism and presenteeism and both depression severity, along with the independent contributions of different symptoms. METHODS: Participants (N = 4953) were employees recruited as part of a larger study to evaluate a mental health smartphone app and were recruited via industry partner organisations and social media. Participants completed in-app assessment which included demographic information, the Patient Health Questionnaire-9 depression tool, and items of the World Health Organization Health and Work Performance Questionnaire. The relationship between depressive symptoms, absenteeism and presenteeism was estimated using both total summed scores and individual symptoms of depression. RESULTS: Univariate linear regression confirmed a negative linear relationship between depression severity and presenteeism, which remained significant after controlling for age, gender, industry, and work position. Similarly, there was a statistically significant relationship between depression severity and the amount of mental health related sickness absence taken over the preceding 28 days. Johnson's relative weights analysis showed contributory differences amongst depression symptoms in relation to presenteeism and absenteeism. DISCUSSION: Significant relationships between depression severity and both absenteeism and presenteeism were present indicating increases in absence and decreases in performance with increasing severity. There existed differences amongst the contribution of specific symptoms of depression to both outcomes of interest. The symptoms that contribute most to absence were more behavioural in nature, whilst those contributing most to presenteeism were more cognitive. These findings have practical implications for clinicians and employers in making treatment and return-to-work decisions.

A smartphone application for treating depressive symptoms: study protocol for a randomised controlled trial.

BACKGROUND: Depression is a commonly occurring disorder linked to diminished role functioning and quality of life. The development of treatments that overcome barriers to accessing treatment remains an important area of clinical research as most people delay or do not receive treatment at an appropriate time. The workplace is an ideal setting to roll-out an intervention, particularly given the substantial psychological benefits associated with remaining in the workforce. Mobile health (mhealth) interventions utilising smartphone applications (apps) offer novel solutions to disseminating evidence based programs, however few apps have undergone rigorous testing. The present study aims to evaluate the effectiveness of a smartphone app designed to treat depressive symptoms in workers. METHODS: The present study is a multicentre randomised controlled trial (RCT), comparing the effectiveness of the intervention to that of an attention control. The primary outcome measured will be reduced depressive symptoms at 3 months. Secondary outcomes such as wellbeing and work performance will also be measured. Employees from a range of industries will be recruited via a mixture of targeted social media advertising and Industry partners. Participants will be included if they present with likely current depression at baseline. Following baseline assessment (administered within the app), participants will be randomised to receive one of two versions of the Headgear application: 1) Intervention (a 30-day mental health intervention focusing on behavioural activation and mindfulness), or 2) attention control app (mood monitoring for 30 days). Participants will be blinded to their allocation. Analyses will be conducted within an intention to treat framework using mixed modelling. DISCUSSION: The results of this trial will provide valuable information about the effectiveness of mhealth interventions in the treatment of depressive symptoms in a workplace context. TRIAL REGISTRATION: The current trial is registered with the Australian and New Zealand Clinical Trials Registry ( ACTRN12617000547347 , Registration date: 19/04/2017).

A novel method to visualise the three-dimensional organisation of the human cerebral cortical vasculature.

Current tissue-clearing protocols for imaging in three dimensions (3D) are typically applied to optimally fixed, small-volume rodent brain tissue - which is not representative of the tissue found in diagnostic neuropathology laboratories. We present a method to visualise the cerebral cortical vasculature in 3D in human post-mortem brain tissue which had been preserved in formalin for many years. Tissue blocks of cerebral cortex from two control cases, two Alzheimer's brains and two cases from Alzheimer's patients immunised against Aß42 were stained with fluorescent Lycopersicon esculentum agglutinin (Tomato lectin), dehydrated and cleared using an adapted three-dimensional imaging of solvent cleared organs (3DISCO) protocol to visualise the vascular endothelium. Tissue was imaged using light sheet and confocal microscopy and reconstructed in 3D using amira software. The method permits visualisation of the arrangement of the parallel penetrating cortical vasculature in the human brain. The presence of four vascular features including anastomosis, U-shaped vessels, spiralling and loops were revealed. In summary, we present a low cost and simple method to visualise the human cerebral vasculature in 3D compatible with prolonged fixation times (years), allowing study of vascular involvement in a range of normative and pathological states.

High-Velocity Microsprays Enhance Antimicrobial Activity in Streptococcus mutans Biofilms.

Streptococcus mutans in dental plaque biofilms play a role in caries development. The biofilm's complex structure enhances the resistance to antimicrobial agents by limiting the transport of active agents inside the biofilm. The authors assessed the ability of high-velocity water microsprays to enhance delivery of antimicrobials into 3-d-old S. mutans biofilms. Biofilms were exposed to a 90° or 30° impact, first using a 1-µm tracer bead solution (109 beads/mL) and, second, a 0.2% chlorhexidine (CHX) or 0.085% cetylpyridinium chloride (CPC) solution. For comparison, a 30-s diffusive transport and simulated mouthwash were also performed. Confocal microscopy was used to determine number and relative bead penetration depth into the biofilm. Assessment of antimicrobial penetration was determined by calculating the killing depth detected by live/dead viability staining. The authors first demonstrated that the microspray was able to deliver significantly more microbeads deeper in the biofilm compared with diffusion and mouthwashing exposures. Next, these experiments revealed that the microspray yielded better antimicrobial penetration evidenced by deeper killing inside the biofilm and a wider killing zone around the zone of clearance than diffusion alone. Interestingly the 30° impact in the distal position delivered approximately 16 times more microbeads and yielded approximately 20% more bacteria killing (for both CHX and CPC) than the 90° impact. These data suggest that high-velocity water microsprays can be used as an effective mechanism to deliver microparticles and antimicrobials inside S. mutans biofilms. High shear stresses generated at the biofilm-burst interface might have enhanced bead and antimicrobial delivery inside the remaining biofilm by combining forced advection into the biofilm matrix and physical restructuring of the biofilm itself. Further, the impact angle has potential to be optimized both for biofilm removal and active agents' delivery inside biofilm in those protected areas where some biofilm might remain.

Streptococcus mutans biofilm transient viscoelastic fluid behaviour during high-velocity microsprays.

Using high-speed imaging we assessed Streptococcus mutans biofilm-fluid interactions during exposure to a 60-ms microspray burst with a maximum exit velocity of 51m/s. S. mutans UA159 biofilms were grown for 72h on 10mm-length glass slides pre-conditioned with porcine gastric mucin. Biofilm stiffness was measured by performing uniaxial-compression tests. We developed an in-vitro interproximal model which allowed the parallel insertion of two biofilm-colonized slides separated by a distance of 1mm and enabled high-speed imaging of the removal process at the surface. S. mutans biofilms were exposed to either a water microspray or an air-only microburst. High-speed videos provided further insight into the mechanical behaviour of biofilms as complex liquids and into high-shear fluid-biofilm interaction. We documented biofilms extremely transient fluid behaviour when exposed to the high-velocity microsprays. The presence of time-dependent recoil and residual deformation confirmed the pivotal role of viscoelasticity in biofilm removal. The air-only microburst was effective enough to remove some of the biofilm but created a smaller clearance zone underlying the importance of water and the air-water interface of drops moving over the solid surface in the removal process. Confocal and COMSTAT analysis showed the high-velocity water microspray caused up to a 99.9% reduction in biofilm thickness, biomass and area coverage, within the impact area.

Rat astrocytic tumour cells are associated with an anti-inflammatory microglial phenotype in an organotypic model.

AIM: Microglia form a high proportion of cells in glial tumours but their role in supporting or inhibiting tumour growth is unclear. Here we describe the establishment of an in vitro model to investigate their role in astrocytomas. METHODS: Rat hippocampal slices were prepared and, after 7 days to allow microglia to become quiescent, rat C6 astrocytic tumour cells were added. Over the following 7 days, infiltration and cell death were studied using fluorescent C6 tumour cells and confocal microscopy; immunophenotyping of microglia was performed using CD68 (phagocytosis), MHCII (antigen-presentation) and Iba1 (microglial marker regardless of functional state). Cell proliferation was assessed using Ki67 and qPCR to detect cytokine expression. Sham and control groups were included. RESULTS: Microscopy showed proliferation of C6 tumour cells with both infiltration of tumour cells into the hippocampal tissue and of microglia among the tumour cells. Confocal experiments confirmed increasing tumour cell infiltration into the hippocampal slice with time (P<0.001), associated with cell death (σ=0.313, P=0.022). Ki67 showed increased proliferation (P<0.001), of both tumour cells and Iba1+ microglia and increased microglial phagocytosis (CD68: P<0.001). Expression of pro-inflammatory cytokines IL1, IL6 and TNFα were downregulated with expression of the anti-inflammatory cytokine TGFß1 maintained. CONCLUSION: This model allows study of the proliferation and infiltration of astrocytic tumour cells in central nervous system tissue and their interaction with microglia. Our data suggest that microglial function is altered in the presence of tumour cells, putatively facilitating tumour progression. Manipulation of the microglial functional state may have therapeutic value for astrocytic tumours.

Self-consistent scaling theory for logarithmic-correction exponents.

Multiplicative logarithmic corrections frequently characterize critical behavior in statistical physics. Here, a recently proposed theory relating the exponents of such terms is extended to account for circumstances which often occur when the leading specific-heat critical exponent vanishes. Also, the theory is widened to encompass the correlation function. The new relations are then confronted with results from the literature, and some new predictions for logarithmic corrections in certain models are made.

Scaling relations for logarithmic corrections.

Multiplicative logarithmic corrections to scaling are frequently encountered in the critical behavior of certain statistical-mechanical systems. Here, a Lee-Yang zero approach is used to systematically analyze the exponents of such logarithms and to propose scaling relations between them. These proposed relations are then confronted with a variety of results from the literature.

Using a 360 degrees diagnostic screening tool to provide an evidence trail of junior doctor performance throughout their first postgraduate year.

New medical graduates in the UK are known as Preregistration House Officers (PRHOs). At the end of this first postgraduate year, the Postgraduate Dean is responsible for allowing the PRHO to be fully registered with the General Medical Council. During the period 1999-2002 Professor Miriam Friedman Ben-David designed a more robust approach to appraisal and assessment of PRHOs, which provided educational feedback to all trainees, allowed any poor performers to be detected at an early stage, and provided 'hard' observable evidence for certification decisions. This paper describes the more recent development of her work resulting from further piloting of her system. The key tool, a 360 degrees diagnostic questionnaire, is designed to identify strengths and weaknesses in individual performance. It is presently being used as a screening tool to identify any trainees needing additional support and further assessment. The tool also forms part of an evidence trail for all PRHOs and helps inform formative assessment as well as contributing, along with other evidence, to full registration decisions. The evaluation of this tool, also described in this paper, shows the feasibility of implementing such a system on a wider scale and illustrates the successful balance made between robustness and feasibility.

A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.

BACKGROUND & AIMS: This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. METHODS: Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. RESULTS: Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). CONCLUSIONS: The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.

Information geometry of the spherical model.

Motivated by the observation that geometrizing statistical mechanics offers an interesting alternative to more standard approaches, we calculate the scaling behavior of the curvature R of the information geometry metric for the spherical model. We find that R approximately epsilon(-2), where epsilon=beta(c)-beta is the distance from criticality. The discrepancy from the naively expected scaling R approximately epsilon(-3) is explained and compared with that for the Ising model on planar random graphs, which shares the same critical exponents.

The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858.

Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.

The changing spectrum of gastroesophageal reflux disease.

The incidences of Barrett's oesophagus and oesophageal adenocarcinoma are rising. However there is no evidence on whether the incidence of gastroesophageal reflux disease is rising. This was a retrospective study investigating the incidence of gastroesophageal reflux disease at endoscopy from 1980 to 1995. The study took place in Tayside, Scotland. Using the Tayside endoscopy database, patients with new diagnoses of Barrett's oesophagus and endoscopic oesophagitis were identified. Cases and rates (per 1000 endoscopies) for oesophagitis, Barrett's oesophagus and combined group of oesophagitis + Barrett's oesophagus were calculated for each year. There was a significant decline in the incidence of oesophagitis. There was a significant large increase in the incidence of Barrett's oesophagus and a small but significant rise in the incidence of endoscopically identified gastroesophageal reflux disease (oesophagitis + Barrett's oesophagus). There was a significant decrease in the ratio of new cases of oesophagitis to new cases of Barrett's oesophagus. At endoscopy there has been a small increase in incidence of gastroesophageal reflux disease. There has, however, been a dramatic change in the spectrum of gastroesophageal reflux disease, with a larger proportion having Barrett's oesophagus than previously.

One-dimensional Potts model, Lee-Yang edges, and chaos.

It is known that the exact renormalization transformations for the one-dimensional Ising model in a field can be cast in the form of the logistic map f(x)=4x(1-x) with x a function of the Ising couplings K and h. The locus of the Lee-Yang zeros for the one-dimensional Ising model in the K,h plane is given by the Julia set of the logistic map. In this paper we show that the one-dimensional q-state Potts model for q> or =1 also displays such behavior. A suitable combination of couplings, which reduces to the Ising case for q=2, can again be used to define an x satisfying f(x)=4x(1-x). The Lee-Yang zeros no longer lie on the unit circle in the complex z=e(h) plane for q not equal 2, but their locus still maps onto the Julia set of the logistic map.

Hydrogeological constraints on riparian buffers for reduction of diffuse pollution: examples from the Bear Creek watershed in Iowa, USA.

Riparian Management Systems (RiMS) have been proposed to minimize the impacts of agricultural production and improve water quality in Iowa in the Midwestern USA. As part of RiMS, multispecies riparian buffers have been shown to decrease nutrient, pesticide, and sediment concentrations in runoff from adjacent crop fields. However, their effect on nutrients and pesticides moving in groundwater beneath buffers has been discussed only in limited and idealized hydrogeologic settings. Studies in the Bear Creek watershed of central Iowa show the variability inherent in hydrogeologic systems at the watershed scale, some of which may be favorable or unfavorable to future implementation of buffers. Buffers may be optimized by choosing hydrogeologic systems where a shallow groundwater flow system channels water directly through the riparian buffer at velocities that allow for processes such as denitrification to occur.

Information geometry of the ising model on planar random graphs.

It has been suggested that an information geometric view of statistical mechanics in which a metric is introduced onto the space of parameters provides an interesting alternative characterization of the phase structure, particularly in the case where there are two such parameters, such as the Ising model with inverse temperature beta and external field h. In various two-parameter calculable models, the scalar curvature R of the information metric has been found to diverge at the phase transition point beta(c) and a plausible scaling relation postulated: R approximately |beta-beta(c)|(alpha-2). For spin models the necessity of calculating in nonzero field has limited analytic consideration to one-dimensional, mean-field and Bethe lattice Ising models. In this paper we use the solution in field of the Ising model on an ensemble of planar random graphs (where alpha=-1, beta=1/2, gamma=2) to evaluate the scaling behavior of the scalar curvature, and find R approximately |beta-beta(c)|(-2). The apparent discrepancy is traced back to the effect of a negative alpha.

A natural history of cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia associated with clavicle hypoplasia and dental abnormalities. The condition is caused by mutations in the CBFA1 gene, a transcription factor that activates osteoblast differentiation. Clinical characteristics associated with CCD have previously been described in case reports and small case series. This study was undertaken to gain a more complete delineation of clinical complications associated with CCD. The study population was composed of 90 CCD individuals and 56 relative controls ascertained from genetic and dental practices in the United States, Canada, Europe, and Australia. A number of previously unrecognized complications were significantly increased including: genua valga, scoliosis, pes planus, sinus infections, upper respiratory complications, recurrent otitis media, and hearing loss. Primary Cesarean section rate was significantly increased compared to relative controls and the general population rate. Finally, dental abnormalities, including supernumerary teeth, failure of exfoliation of the primary dentition, and malocclusion, are serious and complex problems that require intervention. Clinical recommendations based on the results of this study are included.