Cardiovascular and renal profiles in rat offspring that do not undergo catch-up growth after exposure to maternal protein restriction.

Maternal protein restriction is often associated with structural and functional sequelae in offspring, particularly affecting growth and renal-cardiovascular function. However, there is little understanding as to whether hypertension and kidney disease occur because of a primary nephron deficit or whether controlling postnatal growth can result in normal renal-cardiovascular phenotypes. To investigate this, female Sprague-Dawley rats were fed either a low-protein (LP, 8.4% protein) or normal-protein (NP, 19.4% protein) diet prior to mating and until offspring were weaned at postnatal day (PN) 21. Offspring were then fed a non 'growth' (4.6% fat) which ensured that catch-up growth did not occur. Offspring growth was determined by weight and dual energy X-ray absorptiometry. Nephron number was determined at PN21 using the disector-fractionator method. Kidney function was measured at PN180 and PN360 using clearance methods. Blood pressure was measured at PN360 using radio-telemetry. Body weight was similar at PN1, but by PN21 LP offspring were 39% smaller than controls (Pdiet < 0.001). This difference was due to proportional changes in lean muscle, fat, and bone content. LP offspring remained smaller than NP offspring until PN360. In LP offspring, nephron number was 26% less in males and 17% less in females, than NP controls (Pdiet < 0.0004). Kidney function was similar across dietary groups and sexes at PN180 and PN360. Blood pressure was similar in LP and NP offspring at PN360. These findings suggest that remaining on a slow growth trajectory after exposure to a suboptimal intrauterine environment does not lead to the development of kidney dysfunction and hypertension.

Point-of-care echocardiography of the right heart improves acute heart failure risk stratification for low-risk patients: The REED-AHF prospective study.

OBJECTIVES: Validated acute heart failure (AHF) clinical decision instruments (CDI) insufficiently identify low-risk patients meriting consideration of outpatient treatment. While pilot data show that tricuspid annulus plane systolic excursion (TAPSE) is associated with adverse events, no AHF CDI currently incorporates point-of-care echocardiography (POCecho). We evaluated whether TAPSE adds incremental risk stratification value to an existing CDI. METHODS: Prospectively enrolled patients at two urban-academic EDs had POCechos obtained before or <1 h after first intravenous diuresis, positive pressure ventilation, and/or nitroglycerin. STEMI and cardiogenic shock were excluded. AHF diagnosis was adjudicated by double-blind expert review. TAPSE, with an a priori cutoff of ≥17 mm, was our primary measure. Secondary measures included eight additional right heart and six left heart POCecho parameters. STRATIFY is a validated CDI predicting 30-day death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and acute myocardial infarction or coronary revascularization in ED AHF patients. Full (STRATIFY + POCecho variable) and reduced (STRATIFY alone) logistic regression models were fit to calculate adjusted odds ratios (aOR), category-free net reclassification index (NRIcont ), ΔSensitivity (NRIevents ), and ΔSpecificity (NRInonevents ). Random forest assessed variable importance. To benchmark risk prediction to standard of care, ΔSensitivity and ΔSpecificity were evaluated at risk thresholds more conservative/lower than the actual outcome rate in discharged patients. RESULTS: A total of 84/120 enrolled patients met inclusion and diagnostic adjudication criteria. Nineteen percent experiencing the primary outcome had higher STRATIFY scores compared to those event free (233 vs. 212, p = 0.009). Five right heart (TAPSE, TAPSE/PASP, TAPSE/RVDD, RV-FAC, fwRVLS) and no left heart measures improved prediction (p < 0.05) adjusted for STRATIFY. Right heart measures also had higher variable importance. TAPSE ≥ 17 mm plus STRATIFY improved prediction versus STRATIFY alone (aOR 0.24, 95% confidence interval [CI] 0.06-0.91; NRIcont  0.71, 95% CI 0.22-1.19), and specificity improved by 6%-32% (p < 0.05) at risk thresholds more conservative than the standard-of-care benchmark without missing any additional events. CONCLUSIONS: TAPSE increased detection of low-risk AHF patients, after use of a validated CDI, at risk thresholds more conservative than standard of care.

Lycopene-rich diets modulate HDL functionality and associated inflammatory markers without affecting lipoprotein size and distribution in moderately overweight, disease-free, middle-aged adults: A randomized controlled trial.

Background: The consumption of lycopene-rich foods may lower cardiovascular disease (CVD) risk. Lycopene circulates in the blood bound to lipoproteins, including high-density lipoproteins (HDLs). Preliminary data from our group showed that increased consumption of tomato-based food or lycopene supplement in middle-aged subjects led to functional changes to HDL's sub-fractions, HDL2 and HDL3. These changes were also associated with a decrease in serum amyloid A (SAA), potentially enhancing their anti-atherogenic properties. Objective: We carried out a comprehensive randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods or lycopene supplements affects HDL functionality and associated inflammatory markers, and lipoprotein subfractions size and distribution. Design: Volunteers (225, aged 40-65 years) were randomly assigned to one of three dietary intervention groups and asked to consume a control diet (low in tomato-based foods, <10 mg lycopene/week), a lycopene-rich diet (224-350 mg lycopene/week), or the control diet with a lycopene supplement (70 mg lycopene/week). HDL2 and HDL3 were isolated by ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum. Systemic and HDL-associated inflammation was assessed by measuring SAA concentrations. HDL functionality was determined by monitoring paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin cholesterol acyltransferase (LCAT) activities. The lipoprotein subfractions profile was assessed by NMR. Results: Lycopene in serum and HDL significantly increased following consumption of both the high tomato diet and lycopene supplement (p ≤ 0.001 for both). Lycopene, either as a tomato-rich food or a supplement, enhanced both serum- and HDL3-PON-1 activities (p ≤ 0.001 and p = 0.036, respectively), while significantly reducing HDL3-SAA-related inflammation (p = 0.001). Lycopene supplement also significantly increased HDL3-LCAT activity (p = 0.05), and reduced the activity of both HDL2- and HDL3-CETP (p = 0.005 and p = 0.002, respectively). These changes were not associated with changes in the subclasses distribution for all lipoprotein fractions or the size of lipoprotein subclasses. Conclusion: Our results showed that dietary lycopene can significantly enhance HDL functionality, without associated changes in particle size and distribution, by modulating the activity of HDL-associated enzymes. Concomitantly, dietary lycopene significantly decreased serum- and HDL3-associated SAA, confirming that SAA may represent a sensitive inflammatory biomarker to dietary change. Clinical Trial Register: (https://www.isrctn.com), ISRCTN34203810.

Hemodynamic profiles by non-invasive monitoring of cardiac index and vascular tone in acute heart failure patients in the emergency department: External validation and clinical outcomes.

BACKGROUND: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes. METHODS: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k = 3 profiles each). The VC was subgrouped de novo into three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone. Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome. RESULTS: The VC had median age 60 years (interquartile range {49-67}), and was 45% (n = 116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p = 0.001, R2 = 0.159). A difference was not detected between profiles in the VC vs. the DC (p = 0.59, R2 = 0.016). VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (p<0.05). No significant differences between profiles were observed for other clinical variables or the 3 clinical risk scores. CONCLUSIONS: Hemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicated de novo in an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.

Right ventricular dysfunction in acute heart failure from emergency department to discharge: Predictors and clinical implications.

BACKGROUND: Among acute heart failure (AHF) inpatients, right ventricular dysfunction (RVD) predicts clinical outcomes independent of left ventricular (LV) dysfunction. Prior studies have not accounted for congestion severity, show conflicting findings on echocardiography (echo) timing, and excluded emergency department (ED) patients. We describe for the first time the epidemiology, predictors, and outcomes of RVD in AHF starting with earliest ED treatment. METHODS: Point-of-care echo and 10-point lung ultrasound (LUS) were obtained in 84 prospectively enrolled AHF patients at two EDs, ≤1 h after first intravenous diuresis, vasodilator, and/or positive pressure ventilation (PPV). Echo and LUS were repeated at 24, 72, and 168 h, unless discharged sooner (n = 197 exams). RVD was defined as <17 mm tricuspid annulus plane systolic excursion (TAPSE), our primary measure. To identify correlates of RVD, a multivariable linear mixed model (LMM) of TAPSE through time was fit. Possible predictors were specified a priori and/or with p ≤ 0.1 difference between patients with/without RVD. Data were standardized and centered to facilitate comparison of relative strength of association between predictors of TAPSE. Survival curves for a 30-day death or AHF readmission primary outcome were assessed for RVD, LUS severity, and LVEF. A multivariable generalized linear mixed model (GLMM) for the outcome was used to adjust RVD for LVEF and LUS. RESULTS: 46% (n = 39) of patients at ED arrival showed RVD by TAPSE (median 18 mm, interquartile range 13-23). 18 variables with p ≤ 0.1 unadjusted difference with/without RVD, and 12 a priori predictors of RVD were included in the multivariable LMM model of TAPSE through time (R2 = 0.76). Missed antihypertensive medication (within 7 days), ED PPV, chronic obstructive pulmonary disease history, LVEF, LUS congestion severity, and right ventricular systolic pressure (RVSP) were the strongest multivariable predictors of RVD, respectively, and the only to reach statistical significance (p < 0.05). 30-day death or AHF readmission was associated with RVD at ED arrival (hazard ratio {HR} 3.31 {95%CI: 1.28-8.53}, p = 0.009), ED to discharge decrease in LUS (HR 0.11 {0.01-0.85}, p < 0.0001 for top quartile Δ), but not LVEF (quartile 2 vs. 1 HR 0.78 {0.22-2.68}, 3 vs. 1 HR 0.55 {0.16-1.92}, 4 vs. 1 HR 0.32 {0.09-1.22}, p = 0.30). The area under the receiver operating curve on GLMM for the primary outcome by TAPSE (p = 0.0012), ΔLUS (p = 0.0005), and LVEF (p = 0.8347) was 0.807. CONCLUSION: In this observational study, RVD was common in AHF, and predicted by congestion on LUS, LVEF, RVSP, and comorbidities from ED arrival through discharge. 30-day death or AHF-rehospitalization was associated with RVD at ED arrival and ΔLUS severity, but not LVEF.

Unconventionally Acquired Brain Injury: Guidance and Instruction About an Emerging Challenge to Warfighter Brain Health.

Special Operations Forces have made brain health a medical priority in recent years, and new guidance identified a new challenge-unconventionally acquired brain injury (UBI). Although this emerging condition is described as a cluster of neurosensory and cognitive symptoms with unknown etiology/ origin, there remain critical questions about how this diagnosis differs from other brain injuries. More importantly, there are limited recommendations about how medical personnel should approach the problem. The current discussion will provide context and information about UBI based on higher guidance and will also review the scant literature to provide context. Foremost, UBI can be distinguished from traumatic brain injury (TBI) largely due to an unknown point of injury. The described symptoms otherwise appear to be largely the same as TBI. Likewise, the recommended course of treatment is to follow the Clinical Practice Guidelines for mild TBI/TBI even if the injury is an actual or suspected UBI. Personnel must be careful to avoid entering sensitive information into the medical record, which may be particularly challenging if identifying the cause involves classified information about an unconventional weapon. Finally, we briefly discuss the literature about several suspected incidents fitting UBI diagnostic criteria, and we conclude with five primary takeaways for medical personnel to follow.

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aß1-42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes.

Due to an aging population, neurodegenerative diseases such as Alzheimer's disease (AD) have become a major health issue. In the case of AD, Aß1 - 42 peptides have been identified as one of the markers of the disease with the formation of senile plaques via their aggregation, and could play a role in memory impairment and other tragic syndromes associated with the disease. Many studies have shown that not only the morphology and structure of Aß1 - 42 peptide assembly are playing an important role in the formation of amyloid plaques, but also the interactions between Aß1 - 42 and the cellular membrane are crucial regarding the aggregation processes and toxicity of the amyloid peptides. Despite the increasing amount of information on AD associated amyloids and their toxicity, the molecular mechanisms involved still remain unclear and require in-depth investigation at the local scale to clearly decipher the role of the sequence of the amyloid peptides, of their secondary structures, of their oligomeric states, and of their interactions with lipid membranes. In this original study, through the use of Atomic Force Microscopy (AFM) related-techniques, high-speed AFM and nanoInfrared AFM, we tried to unravel at the nanoscale the link between aggregation state, structure and interaction with membranes in the amyloid/membrane interaction. Using three mutants of Aß peptides, L34T, oG37C, and WT Aß1 - 42 peptides, with differences in morphology, structure and assembly process, as well as model lipidic membranes whose composition and structure allow interactions with the peptides, our AFM study coupling high spatial and temporal resolution and nanoscale structure information clearly evidences a local correlation between the secondary structure of the peptides, their fibrillization kinetics and their interactions with model membranes. Membrane disruption is associated to small transient oligomeric entities in the early stages of aggregation that strongly interact with the membrane, and present an antiparallel ß-sheet secondary structure. The strong effect on membrane integrity that exists when these oligomeric Aß1 - 42 peptides interact with membranes of a particular composition could be a lead for therapeutic studies.

Stillbirth in Australia 1: The road to now: Two decades of stillbirth research and advocacy in Australia.

Stillbirth is a major public health problem with an enormous mortality burden and psychosocial impact on parents, families and the wider community both globally and in Australia. In 2015, Australia's late gestation stillbirth rate was over 30% higher than that of the best-performing countries globally, highlighting the urgent need for action. We present an overview of the foundations which led to the establishment of Australia's NHMRC Centre of Research Excellence in Stillbirth (Stillbirth CRE) in 2017 and highlight key activities in the following areas: Opportunities to expand and improve collaborations between research teams; Supporting the conduct and development of innovative, high quality, collaborative research that incorporates a strong parent voice; Promoting effective translation of research into health policy and/or practice; and the Regional and global work of the Stillbirth CRE. We highlight the first-ever Senate Inquiry into Stillbirth in Australia in 2018. These events ultimately led to the development of a National Stillbirth Action and Implementation Plan for Australia with the aims of reducing stillbirth rates by 20% over the next five years, reducing the disparity in stillbirth rates between advantaged and disadvantaged communities, and improving care for all families who experience this loss.

Analysis of structure and gene expression in developing kidneys of male and female rats exposed to low protein diets in utero.

A maternal low protein (LP) diet in rodents often results in low nephron endowment and renal pathophysiology in adult life, with outcomes often differing between male and female offspring. Precisely how a maternal LP diet results in low nephron endowment is unknown. We conducted morphological and molecular studies of branching morphogenesis and nephrogenesis to identify mechanisms and timepoints that might give rise to low nephron endowment. Sprague-Dawley rats were fed a normal protein (19.4% protein, NP) or LP (9% protein) diet for 3 weeks prior to mating and throughout gestation. Embryonic day 14.25 (E14.25) kidneys from males and females were either cultured for 2 days after which branching morphogenesis was quantified, or frozen for gene expression analysis. Real-time PCR was used to quantify expression of key nephrogenesis and branching morphogenesis genes at E14.25 and 17.25. At E17.25, nephron number was determined in fixed tissue. There was no effect of either maternal diet or sex on branching morphogenesis. Nephron number at E17.25 was 14% lower in male and female LP offspring than in NP controls. At E14.25 expression levels of genes involved in branching morphogenesis (Gfrα1, Bmp4, Gdnf) and nephrogenesis (Hnf4a, Pax2, Wnt4) were similar in the dietary groups, but significant differences between sexes were identified. At E17.25, expression of Gfrα1, Gdnf, Bmp4, Pax2 and Six2 was lower in LP offspring than NP offspring, in both male and female offspring. These findings provide new insights into how a LP diet leads to low nephron endowment and renal sexual dimorphism.

Impact of stressful death or divorce in people with HIV: A prospective examination and the buffering effects of religious coping and social support.

This study examined the impact of a stressful death/divorce on psychological and immune outcomes in people with HIV. People with HIV with stressful death/divorce were examined from before the event to up to 12 months later (n = 45); controls were assessed at similar intervals (n = 112). Stressful deaths/divorces were associated with increased viral load and anxiety over time (ps ≤ .014), but not CD4+ or depression. Increased use of religious coping after the stressful death/divorce was associated with slower increases in viral load (p = .010). These data suggest people with HIV should consider the potentially elevated risk of transmission after such events and seek appropriate monitoring and care.

Disrupting gender norms in health systems: making the case for change.

Restrictive gender norms and gender inequalities are replicated and reinforced in health systems, contributing to gender inequalities in health. In this Series paper, we explore how to address all three through recognition and then with disruptive solutions. We used intersectional feminist theory to guide our systematic reviews, qualitative case studies based on lived experiences, and quantitative analyses based on cross-sectional and evaluation research. We found that health systems reinforce patients' traditional gender roles and neglect gender inequalities in health, health system models and clinic-based programmes are rarely gender responsive, and women have less authority as health workers than men and are often devalued and abused. With regard to potential for disruption, we found that gender equality policies are associated with greater representation of female physicians, which in turn is associated with better health outcomes, but that gender parity is insufficient to achieve gender equality. We found that institutional support and respect of nurses improves quality of care, and that women's empowerment collectives can increase health-care access and provider responsiveness. We see promise from social movements in supporting women's reproductive rights and policies. Our findings suggest we must view gender as a fundamental factor that predetermines and shapes health systems and outcomes. Without addressing the role of restrictive gender norms and gender inequalities within and outside health systems, we will not reach our collective ambitions of universal health coverage and the Sustainable Development Goals. We propose action to systematically identify and address restrictive gender norms and gender inequalities in health systems.

Gender equality and gender norms: framing the opportunities for health.

The Sustainable Development Goals offer the global health community a strategic opportunity to promote human rights, advance gender equality, and achieve health for all. The inability of the health sector to accelerate progress on a range of health outcomes brings into sharp focus the substantial impact of gender inequalities and restrictive gender norms on health risks and behaviours. In this paper, the fifth in a Series on gender equality, norms, and health, we draw on evidence to dispel three myths on gender and health and describe persistent barriers to progress. We propose an agenda for action to reduce gender inequality and shift gender norms for improved health outcomes, calling on leaders in national governments, global health institutions, civil society organisations, academic settings, and the corporate sector to focus on health outcomes and engage actors across sectors to achieve them; reform the workplace and workforce to be more gender-equitable; fill gaps in data and eliminate gender bias in research; fund civil-society actors and social movements; and strengthen accountability mechanisms.

Reverse Total Shoulder Arthroplasty for Geriatric Proximal Humerus Fracture Dislocation With Concomitant Nerve Injury.

INTRODUCTION: Preoperative axillary nerve palsy is a contraindication to reverse total shoulder arthroplasty (rTSA) due to the theoretical risk of higher dislocation rates and poor functional outcomes. Treatment of fracture-dislocations of the proximal humerus with rTSA is particularly challenging, as these injuries commonly present with concomitant neurologic and soft tissue injury. The aim of the current study was to determine the efficacy of rTSA for this fracture pattern in geriatric patients presenting with occult or profound neurologic injury. METHODS: A retrospective case series of all shoulder arthroplasty procedures for proximal humerus fractures from February 2006 to February 2018 was performed. Inclusion criteria were patients aged greater than 65 years at the time of surgery, fracture-dislocations of the proximal humerus, and treatment with rTSA. Patients with preoperative nerve injuries were compared to patients without overt neurologic dysfunction. Forward elevation, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), Visual Analog Scale (VAS), and Subjective Shoulder Value (SSV) were obtained at final follow-up. RESULTS: Forty-six rTSA for acute fracture were performed during the study period, 16 patients met the inclusion criteria and 5 (31%) presented with overt preoperative nerve injuries. At mean 3.1 years follow up, there were no postoperative complications including dislocations and final forward elevation was similar between study groups. Patients with overt nerve palsy had higher QuickDASH and VAS scores with lower SSV and self-rated satisfaction. DISCUSSION: In the majority of patients with or without overt nerve injury, rTSA reliably restored overhead function and led to good or excellent patient-rated treatment outcomes. Overt nerve palsy did not lead to higher complication rates, including dislocation. Despite greater disability and less satisfaction, complete or partial nerve recovery can be expected in the majority of patients. CONCLUSION: Nerve injury following proximal humeral fracture dislocation may not be an absolute contraindication to rTSA.

Characterisation of a pucBA deletion mutant from Rhodopseudomonas palustris lacking all but the pucBAd genes.

Rhodopseudomonas palustris is a species of purple photosynthetic bacteria that has a multigene family of puc genes that encode the alpha and beta apoproteins, which form the LH2 complexes. A genetic dissection strategy has been adopted in order to try and understand which spectroscopic form of LH2 these different genes produce. This paper presents a characterisation of one of the deletion mutants generated in this program, the pucBAd only mutant. This mutant produces an unusual spectroscopic form of LH2 that only has a single large NIR absorption band at 800 nm. Spectroscopic and pigment analyses on this complex suggest that it has basically a similar overall structure as that of the wild-type HL LH2 complex. The mutant has the unique phenotype where the mutant LH2 complex is only produced when cells are grown at LL. At HL the mutant only produces the LH1-RC core complex.

Reversible DNA micro-patterning using the fluorous effect.

We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences.

Synthetic toxic Aß1-42 oligomers can assemble in different morphologies.

BACKGROUND: Alzheimer's disease is the most common neurodegenerative disease associated with aggregation of Aß peptides. Aß toxicity is mostly related to the capacity of intermediate oligomers to disrupt membrane integrity. We previously expressed Aß1-42 in a eukaryotic cellular system and selected synthetic variants on their sole toxicity. The most toxic mutant G37C forms stable oligomers. METHODS: Different biophysical methods (Fluorescence spectroscopy, cross-linking, mass spectrometry (MS), Small Angle X-ray Scattering (SAXS), Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), calcein leakage) were used. RESULTS: The oligomers are mostly populated by a 14mers resulting from the packing of homodimers. These homodimers come from the formation of a disulfide bridge between two monomers. This link stabilizes the multimers and prevents the assembly into amyloid fibrils. These oligomers affect the membrane integrity. The reduction of disulfide bonds leads to a rearrangement and redirects assembly of Aß amyloid fibrils. CONCLUSION: The toxic synthetic AßG37C mutant can assemble into an amyloid of unusual morphology through the formation of anti-parallel ß-sheets. This pathway involves the formation of oligomers resulting from the arrangement of Aß dimers linked by covalent di-sulfide link, being these oligomers harmful for the membranes. GENERAL SIGNIFICANCE: The capacity to produce large amount of stable oligomers without additional detergents or extrinsic cross-linkers allow further structural and biophysical studies to understand their capacity to assemble and disrupt the membranes, a key event in Alzheimer's disease.

Feigned Adjudicative Incompetence.

Psychological assessments are highly dependent on the forthrightness and sincere efforts of examinees. In particular, evaluations in forensic settings must consider whether feigning or other response styles are utilized to intentionally distort the clinical presentation. The current study examines the effectiveness of the Inventory of Legal Knowledge (ILK) at detecting feigned incompetency within a sample of jail detainees. As an ancillary goal, several scales of the Standardized Assessment of Miranda Abilities were included in the same within-subjects simulation design. Results of the total ILK score raised concerns regarding the mischaracterization of genuine offenders as "suggestive of feigning." Pending cross-validation, however, a Revised ILK proved highly effective, using a floor effect detection strategy. Although intended for Miranda-specific abilities, several detection strategies on the Standardized Assessment of Miranda Abilities appeared to be very promising within a broadened context of feigned incompetency.

Dodging Self-Incriminations: An Examination of Feigned Miranda Abilities on the SAMA.

Forensic assessments must always consider whether examinees are putting forth genuine effort or seeking to feign legally relevant incapacities. Miranda abilities are no exception when a putatively invalid Miranda waiver might result in the full suppression of an outright confession. Using a within-subjects simulation design, jail detainees were administered a representative Miranda warning and two Standardized Assessment of Miranda Abilities (SAMA) measures: Miranda Vocabulary Scale and Miranda Quiz. As expected, detainees have no difficulty in feigning severe deficits in their recall of the Miranda warning and portraying markedly impaired abilities on both SAMA measures. However, using floor-effect detection strategies, several feigning indicators proved effective at identifying likely feigned Miranda abilities. As an ancillary issue, the Inventory of Legal Knowledge was found to be very effective using both the traditional and revised scoring.

Taking on the gender challenge in organisations: what does it take?

Clear patterns emerged and are summarised on conditions for success in integrating a gender equality perspective across organisational programmes and culture. In short, organisations should consider five key 'ingredients' when designing their approach to integrating a gender equality perspective: (1) have a clear vision of success with measurable indicators; (2) have high-level, consistent, visible support; (3) take an intentional approach deeply rooted in the organisational culture and competencies; (4) ensure accountability at all levels and (5) invest both financial and technical resources. A vibrant community exists in virtually every region of the world of highly experienced gender equality experts that can support organisations on this path. Late adopters of integrating a gender equality perspective can benefit from decades of practice and a robust evidence base which has shifted focus among development organisations from asking 'why' addressing gender inequalities is important to learning 'how' to most effectively do this in programmes, policies, research and organisational culture while building a strong results framework.