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Sensor-integrated needles with impedance or other electrochemical sensors have gained increased attention in research. Their potential use is widespread and covers applications such as early disease diagnostics or needle guidance for needle-based interventions. However, fabrication and sensor integration are crucial parts of realizing functionalized needles. In this paper, a review of existing research on microscale sensor arrays on curved needle surfaces is presented. It focusses on medical needles excluding needle-type sensors. Especially, means of fabrications including flexible thin-film-based sensors or photolithography are discussed. Although they provide satisfactory results, no manufacturing method is yet ready for bulk production.

BACKGROUND: The etiology of atraumatic rotator cuff tears is not completely understood. Limited data suggest the role of genetic and familial predisposition in the etiology of rotator cuff tears. The purpose of this study was to assess whether there is an increased likelihood of rotator cuff tears in family members of patients with rotator cuff tears vs. those without tears. This would provide evidence for whether there is an association between familial predisposition and rotator cuff tearing. METHODS: Patients presenting to a shoulder clinic were recruited in this study. They provided information on personal medical history, shoulder symptoms, and family history of rotator cuff tears. The diagnosis of rotator cuff tears was based on imaging (magnetic resonance imaging or computed tomography arthrogram) confirmation of a structural defect in the rotator cuff. The association between family history of rotator cuff problems and the likelihood of an imaging-confirmed rotator cuff tear diagnosis was evaluated using multivariate logistic regression, adjusting for age, sex, race/ethnicity, cigarette smoking, hypertension, diabetes, and depression. RESULTS: In our cohort of 2335 patients, 52.6% (n = 1229) of patients had a rotator cuff tear. Among patients with tears, 17.9% (n = 0220) of patients reported a family history of rotator cuff issues vs. 11.1% (n = 123) in patients without tears. A family history of rotator cuff problems was significantly associated with the diagnosis of an imaging-confirmed rotator cuff tear (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.71, 2.95). Other confounding variables such as increasing age (OR 1.06, 95% CI 1.05, 1.07) and Hispanic race/ethnicity as compared to non-Hispanic white race/ethnicity (OR 1.48, 95% CI 1.07, 2.05) were significantly associated with rotator cuff tears. Sex, smoking, hypertension, diabetes, and depression were not significantly associated with rotator cuff tearing. CONCLUSION: Our study shows that individuals with rotator cuff tears were more than 2 times as likely to have a family member with a tear as compared to patients without tears. Increasing age and patients who identified as being of Hispanic ancestry were also significantly associated with higher odds of rotator cuff tears. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Design; Prognosis Study

Se determinaron índices de digestibilidad del tracto total (DTT) en dietas de miel de caña de azúcar del tipo B y harina de soya (67.6/30.4%, base seca), formuladas para contener 0, 5, 10 ó 15% de harina de follaje de albizia (Albizia lebbeck (L.) Benth.), brindadas de forma completamente aleatorizadas a 32 cerdos de 30 kg de peso vivo. La DTT de MS, materia orgánica y energía decrecieron significativamente (P=0.001) al aumentar la proporción del follaje en el alimento. La DTT de fibra cruda y FDA mostraron resultados similares (P=0.001), pero no FDN. El cálculo de la DTT de proteína y energía, hecho por diferencia reveló valores de 71.7 y 57.6%, respectivamente, en la harina de follaje de albizia. El consumo de 15% de harina de follaje de albizia en la dieta suministrada en condiciones ad libitum a cerdos de crecimiento, puede determinar cambios perceptibles en los índices de DTT cuando se proporciona a los animales alimentados con dietas de miel de caña de azúcar del tipo B.

Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety.The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed.This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

There have been no studies assessing the acceptability of opioid tapering in the pre-arthroplasty setting. This qualitative study aimed to (1) explore barriers and facilitators to opioid tapering amongst patients with chronic non-cancer pain (CNCP), and (2) explore the similarities and differences in acceptability of opioid tapering between pre-arthroplasty patients and those participating in a biopsychosocial pain management program.From January 2021, adult participants diagnosed with CNCP and taking opioids daily (any dose at time of screening for a period of 3 months) were recruited from either Fairfield Orthopaedic Hip and Knee Service (FOHKS) or Liverpool Hospital Pain Clinic (LHPC). Semi-structured interviews underwent thematic analysis using the framework method.17 participants were recruited (FOHKS, n=9, mean age 67, female 77%, LHPC, n=8, mean age 54, female 63%). Both groups had participants who; (i) were reluctant to use opioid medications and used them out of “necessity”, (ii) were reluctant to taper due to concerns of worsening pain, quality of life, (iii) believed opioids were “toxins” causing bodily harm. Some FOHKS participants believed tapering should be a post-operative focus, whilst others believed tapering opioids pre-operatively will assist in post-op pain management. Few LHPC participants felt dependent/addicted to opioids, thus driving their intention to taper opioids.The belief of tapering opioids causing worse pain was based on either previous experiences or concerns alone. Some FOHKS participants were more inclined to taper opioids if they were educated on the chronic and peri-operative risks associated with using opioids at time of arthroplasty.Opioid users recognise the harms associated with chronic opioid use and believe they are used out of desperation for adequate analgesia, function, and quality of life. Tapering opioids in the pre-arthroplasty context may need coupling with patient education highlighting the importance of opioid tapering pre-operatively.

Introduction Recent trials have shown early de-escalation of empiric antimicrobial therapy (EAT) in febrile neutropenia has led to less adverse effects with no difference in patient mortality. In 2019, our institution adjusted internal guidelines to de-escalate EAT after 7 days of intravenous anti-pseudomonal therapy in patients with signs of clinical recovery from febrile neutropenia and no evidence of infection. Methods This was a retrospective, single-center, observational, cohort study. Eligible patients were adults with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received induction chemotherapy and developed febrile neutropenia without documented infection. Patients were separated based on EAT duration: ≤ 9 days and > 9 days. Empiric antimicrobial therapy was defined as the initiation of an anti-pseudomonal beta-lactam. The primary outcome was the difference in number of EAT-free days. Secondary outcomes included fever recurrence, ICU admissions, fever duration, infections post de-escalation, and Clostridioides difficile infection (CDI). Results Forty-four encounters met inclusion. The EAT ≤ 9 days group had 7 more EAT-free days compared to the EAT > 9 days group (p 9 days group experienced longer initial fever (p < 0.001) and received addition of resistant Gram-positive coverage (p = 0.014). More patients receiving EAT > 9 days had a diagnosis of AML (p = 0.001). Conclusions Shorter EAT duration did not lead to worse outcomes in patients with AML or ALL who received induction chemotherapy and developed febrile neutropenia without a documented infection source.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

An integrated analysis of laser induced breakdown (LIB) and the associated micro-cavitation in a water-like bio-tissue is developed in this study. With this integrated analysis using minimum experimentally fitted parameters, threshold energies of LIB in bio-tissue under different numerical apertures of the focusing lenses can be determined, which provides similar values as the corresponding experimental measurements. The integrated analysis can also determine the electron temperature and number density when LIB is triggered, which also fall in the same order as the corresponding experimental measurements. In addition, the rapid size increment of plasma plume through laser supported detonation wave during a LIB can be observed with the integrated analysis. The developed integrated analysis becomes unstable when strong pressure wave presents due to strong heating and the following rapid expansion of the bio-tissue under higher input laser energy (compared with the threshold energy of LIB). Therefore, for simulating high energy LIB and the following micro-cavitation in a bio-tissue, a more advanced numerical scheme that can better capture the propagation of pressure wave will be required in the future.

The caudal-related homeobox transcription factor 2 (CDX2) plays an important role in intestinal epithelial differentiation, proliferation, migration, and adhesion. It has been previously reported that TNF-α reduces CDX2 expression in cultured colon epithelial cells in a dose-dependent manner, and that this effect was reduced by adding the anti-TNF-α drug infliximab to the culture medium. The aim of this study was to determine whether CDX2 expression is reduced in biopsies from patients with Crohn's disease (CD), and whether treatment with anti-TNF-α drugs reverses CDX2 downregulation in these patients.Sections of ileocolonic biopsy tissues from patients with CD, CD treated with anti-TNF-α biologics (CD-T), and controls were stained for CDX2 and evaluated using OTMIAS digital image analysis.CDX2 expression in biopsies from patients with CD and CD-T was lower than in controls (Although CDX2 is downregulated in CD, it did not revert to normal in patients treated with anti-TNF-α biologics.

CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-β1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-β1 expression in SSA is unknown. The aim of this study is to determine ER-β1 expression in SSA and its relation to CDX2 expression.Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-β1 and CDX2. SSA with ER-β1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in10% of SSA crypts as 1, 11-25% as 2, 26-50% as 3, 51-75% as 4, and CDX2 loss in75% of the SSA crypts scored as 5.There is a significant correlation between a loss of CDX2 and the loss of ER-β1 scores in SSA (Our findings show significant downregulation of both ER-β1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-β1 downregulation plays a significant role in the malignant progression of SSA.

Objective Donepezil is widely used to treat Alzheimer’s disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. Method This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). Results The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. Conclusions The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

Breast cancer stem cells (BCSCs) have been shown to be associated with tumor recurrence, metastasis and drug resistance. We reported that the ganglioside GD2 selectively identifies BCSCs and its over-expression in Triple-Negative Breast Cancer (TNBC). However, the factors regulating GD2+ BCSCs in a growing tumor are not known. Here we hypothesize that nutrient deprivation-induced oxidative stress upregulates GD2+ BCSCs in TNBC. TNBC cell lines including SUM159 and MDA-MB-231 were cultured under different nutrient-deprived conditions and analyzed for GD2 expression by flow cytometry. We have identified a steady increase of GD2+ cells from 5%±2% on day 3 to 20%±5% on day 6 in cells cultured in nutrient deprived condition. We further performed the in vivo by injecting GFP+ MDA-MB-231 cells into NSG mice and measured GD2+ expression in the growing tumor once a week. Interestingly, we also noticed a positive correlation between the percentage of GD2+ cells and tumor volume in vivo with r=0.9829 and p Citation Format: Appalaraju Jaggupilli, Stanely J. Ly, Roshan Borkar, Khoa Nguyen, Bin Yuan, Nagireddy Putluri, Michael Andreeff, V. Lokesh Battula. Oxidative stress induces glutamine-dependent GD2+ triple negative breast cancer stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3801.

Background:Biological and targeted synthetic disease modifying anti-rheumatic agents (bDMARDs) increase the risk of serious infections (SIs), however there is limited ‘real-world’ evidence comparing the relative risk of SI for individual bDMARDs. (1,2)Objectives:This study examines the rates of SIs in a non-select Australian Northern Queensland (NQ) cohort of patients with various rheumatic diseases receiving treatment with a bDMARD, to define predisposing factors and directly compare the bDMARDs.Methods:A retrospective review was performed for all patients who received a bDMARD through the Townsville Hospital Rheumatology Department over the 5-year period between June 2013 and May 2018. Episodes of a SI were defined as infection requiring admission or use of intravenous antibiotics. For each bDMARD the rate of SI per 100 patient years (PYs) was calculated and patient demographics and comorbidities were analysed. Between group differences were assessed using independent samples t-tests or ANOVA. Where assumptions were violated, Mann-Whitney U tests or Kruskal-Wallis tests were used. For categorical variables, chi-square tests were used, except when assumptions were violated when Fisher’s Exact tests were used.Results:296 patients received bDMARDs with an overall SI rate of 11.7/100PYs. There was no significant difference in presence of SI by disease type with 24% of patients with rheumatoid arthritis versus 19% with psoriatic arthritis, 14% with ankylosing spondylitis and 29% with “other” (X2=3.11; df=3; p=0.37). Respiratory tract infections were the most common infection (46%) followed by skin and soft tissue infections (23%). The highest incidence rate of SI occurred with rituximab (29.72 SI/100PYs) followed by certolizumab (22.50 SI/100PYs) and tocilizumab (15.00 SI/100PYs). Duration of time on a bDMARD, disease duration and use of methotrexate or leflunomide were not shown to significantly increase the risk of SI for the entire cohort. The characteristics which were shown to significantly increase SI rates were; prednisone use, increasing age, chronic pulmonary comorbidity and specifically in those with rheumatoid arthritis male gender and total duration of bDMARD use.Conclusion:In this real-world NQ cohort of patients treated with a bDMARD for a rheumatic disease, we have identified a number of factors potentially contributing to the risk of the development of SIs. This study provides valuable data on SI rates in an Australian ‘real-world’ cohort that may assist clinicians’ choice of bDMARD in patients with a high baseline risk of infection and highlights the importance of minimising prednisone use in patients on bDMARDs.References:[1]Ramiro S, Sepriano A, Chatzidionysiou K, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1093–1101.[2]Singh J, Wells G, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;16:CD008794.Disclosure of Interests: :Kate Celkys: None declared, Jason Ly: None declared, Muriel Soden Speakers bureau: Speaker Fees from Pfizer in 2016

With high spatial but low temporal coherent nanosecond (ns) green light, ns pulsed illumination phase-contrast microscopy is successfully constructed. The pulsed illumination phase-contrast microscopy can provide ns time resolution to resolve transient dynamics of transparent targets with high contrast ratio that cannot be achieved with traditional bright-field or phase-contrast microscopies. Transient dynamics of laser-induced microcavitation is successfully recorded with this imaging technique to demonstrate its capabilities. In addition to tracing the evolutions of vapor bubbles and shockwaves during a laser-induced microcavitation, this imaging technique can sense the refractive index change of the transparent target during a pressure field variation.

The study aimed at evaluating effect Sweet (Sauropus androgynus L. Merr) leaves meal (SLM) inclusion into feed on performance and Income over Feed Cost (IOFC) of growing pigs. There were 12 landrace crossbred barrows 4-5 months of age with 26.5-55.5kg (CV = 19.69%) initial bodyweight used in a feeding trial. Randomized block design 4 treatments with 3 replicate procedures were applied. The 4 treatment feeds offered in the feeding trial were: (1) T0: 100% basal feed; (2) T1: 97% basal feed + 3% SLM; (3) T2: 94% basal feed + 6% SLM; and (4) T3: 91% basal feed 9% SLM. Variables evaluated were performances (feed intake, weight gain, and feed conversion) and IOFC. Statistical analysis shows that the effect of including SLM into basal feed is not significant (P>0.05) on either performance or IOFC of the pigs. The conclusion is that including Sweet leaves meal inclusion into basal feed performs similar values with basal feed, and up to 9% tends to be higher in performances and IOFC in grower pigs.

Background: Collecting patient reported outcomes (PROs) in oncology clinical trials is becoming increasingly important. However, there is limited consensus on the most appropriate frequency of PRO administration in oncology trials. The aim of this preliminary study is to examine the perspective of participants with a cancer diagnosis on the importance of completing PROs and to identify at what frequency participants prefer to report on their cancer-related symptoms.Methods: 166 participants with a self-reported cancer diagnosis completed a multiple-choice online survey regarding perceptions of symptom importance and reporting preferences.Results: When asked about the benefit of reporting oncology-related symptoms daily, 44% of participants indicated there would be “very much” a benefit, 29% indicated there would be “quite a bit” of benefit, and 17% indicated there would be “somewhat” of a benefit. When asked about how frequently they would prefer to report symptoms, 41% of participants preferred “as they occur,” 36% preferred “once a day,” 18% preferred “once a week,” 4% preferred “twice a day,” and 1% preferred “every 4 hours”.Conclusions: PROs in oncology clinical research are most often collected at weekly, monthly, or longer intervals; however, meaningful fluctuations in cancer-related symptoms can occur more frequently. While concerns regarding patient burden are often raised to support infrequent reporting, these data suggest that participants would like to report symptoms with greater frequency, as episodic and daily reporting options were most popular. Based on these data, more frequent PRO data capture is not only feasible but perceived as important by individuals with cancer.

Electronic capture of patient-reported outcome (PRO) data has many advantages over paper-based data collection. Regulatory agencies have consistently supported the use of electronic PRO (ePRO) data capture and recommended participant and site staff training on the correct use of electronic data capture systems. The objective of this paper is to outline best practice recommendations for training end users, including site staff and study participants, on the use of ePRO technology in clinical trials to enable consistent, accurate, and complete data collection. Site personnel should be trained on study-specific as well as technology-specific topics and be given instructions on whom to contact to obtain technical support. Optimal training takes place over time using multiple modalities, including hands-on, face-to-face training at an investigator meeting or directly in the clinical site; remote training via webinar or teleconference; interactive on-demand self-paced-training via e-learning modalities; and supplemented by proxy training performed by study clinical research associates. Like site personnel training, study participants should be provided with individual, hands-on training by site staff at the initiation of the trial and in conjunction with interactive electronic training modules that can be accessed on-demand throughout the duration of the trial. The recommendations put forth in this paper provide a structured framework for the training that site personnel and study participants need to optimize the advantages trials can gain from using ePRO data collection systems.

Limited studies have shown that some patients with pancreatic adenocarcinoma (PAC) may benefit from treatment with tamoxifen. PAC has been shown to be largely negative for estrogen receptor alpha (ER-alpha). The aim of this pilot study was to investigate ER-beta expression in human PAC. Sections of tissue microarray with 18 evaluable cases of human PAC were stained by immunohistochemistry (IHC) for ER-beta1, ER-beta2, ER-beta5, and Cyclin A. The levels of ER-beta isoform expression and the S-phase fraction (SPF) were determined using quantitative digital image analysis. Higher mean and median ER-beta2 levels correlated with male sex (p = 0.057 and p = 0.035, respectively), older age (p = 0.005 and p = 0.006, respectively), and lower pT stage (p = 0.008 and p = 0.009). Mean and median ER-beta5 levels correlated negatively with SPF (p = 0.021 and p = 0.047, respectively). Mean ER-beta1 expression did not correlate with any of the above mentioned clinicopathologic factors. The findings in this pilot study, although should be considered preliminary, suggest that some ER-beta isoforms may play a role in the biology of PAC. Additional larger studies are needed to confirm our findings, and to determine whether ER-beta may be considered for future targeted therapy.

Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

Stroke management dramatically changed during the last decades. Evidence shows that an early admission in a stroke unit offers the best chance of recovery to the stroke patient. The most spectacular aspect of the stroke unit activity consists of the hyperacute diagnostic and therapeutic stroke procedures, including prompt neuroimaging, intravenous thrombolysis and mechanical thrombectomy.La prise en charge de l’accident vasculaire cérébral s’est considérablement modifiée durant la dernière décennie et continue d’évoluer, au bénéfice direct des patients victimes de cette urgence très fréquente. L’accent est mis sur la prise en charge la plus précoce possible par un centre hospitalier équipé d’une unité neurovasculaire. Celle-ci rassemble une équipe multidisciplinaire de professionnels habitués à prendre en charge cette pathologie : neurologues, neuroradiologues, neurochirurgiens, neuropsychologues, logopèdes, médecins physiques, infirmières. La manifestation la plus visible de cette unité consiste en la prise en charge diagnostique et thérapeutique à l’admission du patient. Celle-ci permet de distinguer rapidement les accidents ischémiques des hémorragies ou des thrombophlébites intracrâniennes puis, dans le cas ischémique, de procéder à la désocclusion de l’artère coupable, soit par thrombolyse intraveineuse, soit par thrombectomie mécanique, ou les deux.

Introduction Cognitive change in people at risk of Alzheimer's disease (AD) such as subjective memory complainers is highly variable across individuals. Methods We used latent class growth modeling to identify distinct classes of nonlinear trajectories of cognitive change over 2 years follow-up from 265 subjective memory complainers individuals (age 70 years and older) of the INSIGHT-preAD cohort. We determined the effect of cortical amyloid load, hippocampus and basal forebrain volumes, and education on the cognitive trajectory classes. Results Latent class growth modeling identified distinct nonlinear cognitive trajectories. Education was associated with higher performing trajectories, whereas global amyloid load and basal forebrain atrophy were associated with lower performing trajectories. Discussion Distinct classes of cognitive trajectories were associated with risk and protective factors of AD. These associations support the notion that the identified cognitive trajectories reflect different risk for AD that may be useful for selecting high-risk individuals for intervention trials.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae , genus Phlebovirus ), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. IMPORTANCE Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to spread into other countries. Vaccination is considered an effective way to prevent the disease, and the only available veterinary RVF vaccine in the United States is a live-attenuated MP-12 vaccine, which is conditionally licensed. Strain MP-12 is different from its parental pathogenic RVFV strain, strain ZH548, because of the presence of 23 mutations. This study determined the role of individual mutations in the attenuation of the MP-12 strain. We found that full attenuation of MP-12 occurs by a combination of multiple mutations. Our findings indicate that a single reversion mutation will less likely cause a major reversion to virulence of the MP-12 vaccine.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

Laser-induced microcavitation refers to the rapid formation and expansion of a vapor bubble inside the bio-tissue when it is exposed to intense, pulsed laser energy. With the associated microscale dissection occurring within the tissue, laserinduced microcavitation is a common approach for high precision bio-surgeries. For example, laser-induced microcavitation is used for laser in-situ keratomileusis (LASIK) to precisely reshape the midstromal corneal tissue through excimer laser beam. Multiple efforts over the last several years have observed unique characteristics of microcavitions in biotissues. For example, it was found that the threshold energy for microcavitation can be significantly reduced when the size of the biostructure is increased. Also, it was found that the dynamics of microcavitation are significantly affected by the elastic modules of the bio-tissue. However, these efforts have not focused on the early events during microcavitation development. In this study, a direct numerical simulation of the microcavitation process based on equation of state of the biotissue was established. With the direct numerical simulation, we were able to reproduce the dynamics of microcavitation in water-rich bio tissues. Additionally, an experimental setup in deionized water and 10% PAA gel was made to verify the results of the simulation for early micro-cavitation formation for 10% Polyacrylamide (PAA) gel in deionized water.

A numerical analysis capable of describing the early stage of a thermal microcavitation process in a water-rich biotissue without avalanche breakdown was developed. The analysis successfully reproduced the laser-induced heating, vapor bubble formation, bubble expansion, and shockwave propagation inside a water-rich biotissue during a thermal microcavitation process. Based on the analysis, it was determined that the evolution of the temperature, pressure, and laser-induced shockwave is dependent on the incident laser energy and laser pulse width. On the other hand, the early stage dynamics of the microcavitation process showed little dependence on the elastic modulus of the biotissue for the laser and tissue conditions studied.

Axial T2-weighted fat-saturated imaging provides information not readily available from routine lumbar spine magnetic resonance imaging (MRI) protocols and routine inclusion of this sequence in place of axial T1-weighted imaging provides additional diagnostic information that can be obtained without increasing examination time or cost. The purpose of this review is to highlight the value of axial T2-weighted fat-saturated imaging as part of a routine lumbar spine MRI protocol.

Background: Patient-reported outcomes play an essential role in evaluating the results of clinical trials. As technological advances are made throughout the industry, pharmaceutical sponsors’ ability to collect field-based patient data has greatly increased. Recently, many clinical trials are utilizing varying modes of data capture in order to enable maximum flexibility. Given the regulatory concern over the equivalence of mixed modes of administration, the need to research the use of varying devices is essential.Methods: This study reviewed three handheld smartphone devices for conceptual equivalence and conducted usability for standard questions used in a daily pain diary. Ten participants, 7 females 3 males; ages 27-70 years, diagnosed with chronic pain or fibromyalgia, completed the same pain diary on three different smartphone devices.Results: Overall, participants reported no differences between these three smartphone devices and found the presentation of the diary content to be similar, if not identical, on all three devices.Conclusions: Device type had no impact on the presentation of the diary content or participants’ understanding of the diary questions.

Background: In migraine clinical trials, patients’ understanding of the terminology used in patient-reported outcome (PRO) measures is important as variability in completing PRO measures can reduce the power to detect treatment efficacy. This study examines patients’ understanding of how to complete PRO measures in the absence of training, if minimal training can improve the accuracy of answering PRO items, and patients’ opinion on the necessity of training and their preference for the method of training.Methods: Participants reporting a diagnosis of migraine completed online surveys. Participants were given scenarios of how to report headache days and pain severity. Respondents were asked about their opinions on the necessity of training, and their preference for the method of training. In a second study, participants were given a hypothetical scenario on how to report pain severity before and after a short training.Results: The majority of participants had different criteria to interpret PRO questions and provided incorrect answers to our scenarios. In the second study, with minimal training, errors were reduced by 7.5%. Over 90% of participants viewed educational materials and training as necessary and preferred electronic modes of training with the ability to review training materials as needed for the duration of the trial.Conclusions: Patient training may improve data quality and inter-rater reliability in clinical trials. Electronic interactive training could be used as an approach to reduce inconsistencies in PRO measures and improve data quality.

Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

Droplet Digital™ polymerase chain reaction (ddPCR™) is a promising technique that quantitates the absolute concentration of nucleic acids in a given sample. This technique utilizes water-in-oil emulsion technology, a system developed by Bio-Rad Laboratories that partitions a single sample into thousands of nanoliter-sized droplets and counts nucleic acid molecules encapsulated in each individual particle as one PCR reaction. This chapter discusses the applications and methodologies of ddPCR for development of Rift Valley fever (RVF) vaccine, using an example that measures RNA copy numbers of a live-attenuated MP-12 vaccine from virus stocks, infected cells, or animal blood. We also discuss how ddPCR detects a reversion mutant of MP-12 from virus stocks accurately. The use of ddPCR improves the quality control of live-attenuated vaccines in the seed lot systems.

Droplet Digital™ polymerase chain reaction (ddPCR™) is a promising technique that quantitates the absolute concentration of nucleic acids in a given sample. This technique utilizes water-in-oil emulsion technology, a system developed by Bio-Rad Laboratories that partitions a single sample into thousands of nanoliter-sized droplets and counts nucleic acid molecules encapsulated in each individual particle as one PCR reaction. This chapter discusses the applications and methodologies of ddPCR for development of Rift Valley fever (RVF) vaccine, using an example that measures RNA copy numbers of a live-attenuated MP-12 vaccine from virus stocks, infected cells, or animal blood. We also discuss how ddPCR detects a reversion mutant of MP-12 from virus stocks accurately. The use of ddPCR improves the quality control of live-attenuated vaccines in the seed lot systems.

BACKGROUND AND PURPOSE Drug candidates must be thoroughly investigated for their potential cardiac side effects. During the course of routine toxicological assessment, the compound RO5657, a CCR5 antagonist, was discovered to have the rare liability of inducing torsades de pointes (polymorphic ventricular arrhythmia) in normal, healthy animals. Studies were conducted to determine the molecular mechanism of this arrhythmia. EXPERIMENTAL APPROACH Toxicological effects of repeat dosing were assessed in naive monkeys. Cardiovascular effects were determined in conscious telemetry-implanted monkeys (repeat dosing) and anaesthetized instrumented dogs (single doses). Mechanistic studies were performed in guinea-pig isolated hearts and in cells recombinantly expressing human cardiac channels. KEY RESULTS In cynomolgus monkeys, RO5657 caused a low incidence of myocardial degeneration and a greater incidence of ECG abnormalities including prolonged QT/QTc intervals, QRS complex widening and supraventricular tachycardia. In telemetry-implanted monkeys, RO5657 induced arrhythmias, including torsades de pointes and in one instance, degeneration to fatal ventricular fibrillation. RO5657 also depressed both heart rate (HR) and blood pressure (BP), with no histological evidence of myocardial degeneration. In the anaesthetized dog and guinea-pig isolated heart studies, RO5657 induced similar cardiovascular effects. RO5657 also inhibited Kv11.1 and sodium channel currents. CONCLUSIONS AND IMPLICATIONS The molecular mechanism of RO5657 is hypothesized to be due to inhibition of cardiac sodium and Kv11.1 potassium channels. These results indicate that RO5657 is arrhythymogenic due to decreased haemodynamic function (HR/BP), decreased conduction and inhibition of multiple cardiac channels, which precede and are probably the causative factors in the observed myocardial degeneration.

Sorption of inorganic elements onto carbonate minerals has been intensively described in the literature by two reaction steps: (1) a first one rapid and completed within a few hours and (2) a second one slower, eventually irreversible, and occurring at a constant rate. The first step is often attributed to an ion-exchange process, but its reversibility is rarely investigated. Consequently, discrimination of the global sorption phenomenon into two different mechanisms is not always justified. In this study, we investigated, by batch experiments, both sorption and desorption of Ca(II), HCO 3 - , and Zn(II), radiolabeled with isotopes 45Ca(II), H 14 CO 3 - , and 65Zn(II), respectively, onto synthetic pure calcite. Solutions were preequilibrated with atmospheric pCO2 and saturated with respect to calcite. Therefore, our purpose was to: (1) obtain experimental distribution coefficients of major elements (Ca(II) and HCO 3 - ) and a trace element (Zn(II)) onto calcite from sorption and desorption experiments, (2) test the validity of a first-occurring ion-exchange process generally noted in the literature, by calculating distribution coefficients for the “sole” exchange process, and (3) quantify the amounts of Ca(II), HCO 3 - , and Zn(II) sorbed on the calcite surface by the sole “exchange process” and compare them with surface crystallochemical data. Ca(II) or HCO 3 - sorption experimental data suggest that a significant fraction of these two elements was sorbed irreversibly onto or in the calcite. By using a method based on isotopic ratios, the Ca(II) or HCO 3 - concentrations, which are reversibly adsorbed on the calcite, have been quantified. These concentrations are respectively estimated at 4.0 ± 2.0 × 10−4 and 7.0 ± 1.5 × 10−4 mol/kg. The obtained Ca(II) surface concentration value is one order of magnitude lower than the one obtained from isotopic measurement by former authors [Geochim. Cosmochim. Acta 55 (1991) 1549; Geochim. Cosmochim. Acta 51 (1987) 1477; Geochim. Cosmochim. Acta 52 (1988) 2281] at the same pH. On the other hand, the kinetics of Zn(II) sorption onto calcite was followed over more than 1000 h. Sorption/desorption experimental results suggest that the sorption is totally reversible at least when total aqueous Zn concentration is less than 10−6 mol/L and when experiments are performed in equilibrium with both calcite and pCO2 = 10−3.5 atm. Under these conditions and at pH 8.3, the occupancy rate of Zn(II) onto the calcite surface is estimated to represent approximately 1% of the total surface-site density.

The receptor tyrosine kinase FLT3 can undergo a series of mutations, including the activating internal tandem duplication (ITD) in the juxtamembrane region and point mutations in the tyrosine kinase domain such as at the activation loop residue D835 (Thiede et al. 2002). FLT3 is widely accepted as a prime target for acute myeloid leukemia (AML) therapy, as the FLT3-ITD mutation is present in approximately 24% of AML patients and it is associated with very poor prognosis (Kottaridis et al. 2003). However, additional acquired mutations of FLT3, including D835 or “gatekeeper” F691 mutations that have been identified in clinical patients who showed resistance/relapse to FLT3 inhibitors sorafenib or quizartinib (Man et al. 2012; Smith et al. 2012), can render most FLT3 inhibitors ineffective. We also reported that aberrant upregulation of other parallel prosurvival signaling pathways may render AML resistant to FLT3-targeted therapy (Zhang et al. 2014). CG′806 is a small-molecule multi-kinase inhibitor against FLT3 and BTK kinases that is under development to treat FLT3-driven AML. A single test concentration of 25 nM in a 583-kinase panel, an IC50 analysis against 176 kinases, and a Kd analysis against 483 kinases illustrated the ability of CG′806 to target the entirety of FLT3-mutant enzymes and to inhibit additional kinases (e.g., BTK, AURK, STE group, and TRK/AXL/DDR group). CG′806 exerted potent picomolar IC50 antiproliferative activity against human AML cells and against Ba/F3 mouse AML cells with FLT3-ITD mutations (about 50 to 250-fold higher activity compared to quizartinib or gilteritinib). Specifically, compared to second-generation FLT3 inhibitors quizartinib or gilteritinib, CG′806 showed much more pronounced antiproliferative effects in leukemia cells with D835 mutations, the ITD plus F691I/Y842D/D835 mutations, or in FLT3 wild-type cells (IC50s were 0.17, 0.82, 9.49, 0.30, 8.26, 9.72, and 0.43 nM for human ITD-mutated AML cells MV4-11 (FLT3-ITD), MOLM13 (FLT3-ITD), murine ITD mutated leukemia cells Ba/F3 WT, Ba/F3-ITD, Ba/F3-D835Y, Ba/FLT3-ITD+D835Y, and “gatekeeper” mutation Ba/F3-ITD+F691L cells, respectively). Furthermore, CG′806 triggered profound apoptosis in cell lines and primary AML patient samples harboring FLT3-ITD mutations as well as WT. Mechanistically, CG′806 profoundly suppressed FLT3 and its downstream MAPK/AKT signaling, as well as phospho-Aurora, and/or phospho-BTK proteins, suggesting the ability of CG′806 to inhibit various kinases that function in AML signaling and appear to contribute to its effectiveness. Moreover, CG′806 demonstrated in vivo tumor eradication without toxicity when administered orally, once daily for 14 d as a single agent in the MV4:11 AML murine xenograft model, and demonstrated sustained micromolar plasma drug levels in mice after a single oral administration. CG′806 can be considered not only a pan-FLT3 inhibitor for targeting FLT3 wild-type and ITD-mutant AML, but also a one-of-a-kind agent killing leukemia cells with TKD or dual TKD plus ITD mutations, which are frequently associated with resistance/relapse in FLT3-mutant AML patients. CG′806 exerts a robust therapeutic window in animal xenograft studies and does not appear to elicit the adverse side effects seen with other multikinase inhibitors (i.e., weight loss, nausea, diarrhea, myelosuppression, and/or vomiting). CG′806 warrants further investigation for the treatment of newly diagnosed and relapsed/refractory patients with FLT3-mutated AML. Citation Format: Weiguo Zhang, Hongying Zhang, Andrea Local, William G. Rice, Charlie J. Ly, Guopan Yu, Stephen B. Howell, Michael Andreeff. CG′806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3 [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr 25.

The aim of this study was to identify risk factors for lupus nephritis including clinical, laboratory, and ethnic factors in a cohort of lupus patients in New Zealand. A retrospective study of patients from two teaching hospitals in Auckland, New Zealand. Patients were selected if they had attended as either an inpatient, or a rheumatology outpatient between 2000 and 2005. 170 patients had SLE according to ACR classification. Lupus nephritis (LN) was diagnosed according to ACR criteria. Clinical, laboratory, and ethnic data were gathered from the patient notes. Twenty-four patients had LN at diagnosis and 32 patients developed LN after diagnosis. LN was associated with serositis ( P = 0.008), cutaneous vasculitis ( P = 0.026), anaemia ( P = 0.005), CRP elevation >6 months ( P < 0.001), hypocomplementaemia >6 months ( P < 0.0001). Patients with elevated doublestranded DNA (dsDNA) (>5 × normal) were more likely to develop type IV LN ( P = 0.0096). Forty-one percent of patients were Caucasian, 12% Maori, 23% Pacific People, 16% Asian, 6% Indian. Maori patients with SLE (odds ratio (OR) = 8.47, 95% confidence interval (CI) = 2.11—33.96, P = 0.002), and Pacific People (OR = 3.11, 95% CI = 1.29—11.48, P = 0.014) had increased risk for developing LN. Anaemia at presentation (hazard ratio (HR) 3.2, 95% CI = 1.4—7.1, P = 0.004), and low complement >6 months (HR = 3.4, 95% CI = 1.4—8.7, P = 0.008) were independent risk factors for developing LN after SLE diagnosis. In New Zealand, Pacific People and Maori patients with SLE have a higher incidence of LN, and patients with anaemia and hypocomplementaemia are more likely to develop LN after diagnosis. Patients with high dsDNA levels are more likely to develop Type IV lupus nephritis. Lupus (2007) 16, 830—837.