Hysteresis in phase volumes, compositions and interfacial roughness in model OPV-small-molecule/polymer thin-films.

Domain morphology and composition, and the structure of interfaces between domains are key factors in the performance and stability of organic photovoltaics (OPVs) fabricated from polymer/small-molecule blends. In this study, we investigate the evolution of composition, phase-volume and interfacial roughness in model polymer/small-molecule bilayers, in response to thermal annealing. Polystyrene/fullerene mixing is studied as a function of annealing temperature, using in situ neutron reflectivity, in thin-film bilayer samples comprising pure component or mixed layers. Remarkably, we discover that thermal annealing at temperatures around or above the reported glass transition temperatures, Tg, of the components can result in extensive mass-transfer between layers, that has the superficial appearance of equilibration, but leaves the layer compositions, thicknesses, and/or the interfacial composition profile in a non-equilibrium state. This is not merely a case of slow kinetics near Tg, as subsequent heating to higher temperatures, followed by cooling, reveals pronounced hysteresis in these systems. This has important implications for the measurement of equilibrium compositions in polymer/small-molecule mixtures for OPV applications, and for device stability during operation.

Comparison of dilute and nondilute osmotic equilibrium models for erythrocytes.

Successful cryopreservation requires the addition of cryoprotective agents (CPAs). The addition of permeating CPAs, such as glycerol, is associated with some risk to the cells and tissues. These risks are both related to the CPA themselves (CPA toxicity) and to the volume response of the cell (osmotic damage). To minimize the potential for damage during cryopreservation, mathematical models are often employed to understand the interactions between protocols and cell volume responses. In the literature, this volume response is usually captured using ideal and dilute approximations of chemical potential and osmolality, an approach that has been called into question for cells in high concentrations of CPAs. To address this, the relevance of non-ideal and non-dilute models has been explored in a number of cell types in the presence of permeating CPAs. However, it has not been explored in erythrocytes, which have a cytosolic hemoglobin content of more than 20% by volume and are cryopreserved in 40% glycerol. Because hemoglobin has been suggested to be a highly non-ideal solute, if the non-ideal and non-dilute transport model is relevant to any cells, it should be relevant to erythrocytes. Here we investigate the use, and accuracy, of both the dilute and non-dilute models in predicting cell volume changes during CPA equilibration in erythrocytes, and demonstrate that using published values for the non-ideal and non-dilute model, applied to erythrocytes, leads to model predictions inconsistent with experimental data, whereas dilute approximations align well with experimental data.

Liquid-liquid equilibrium in polymer-fullerene mixtures; an in situ neutron reflectivity study.

The composition profiles of a series of model polystyrene/fullerene bilayers are measured, before, during and after thermal annealing, using in situ neutron reflectometry. In combination with grazing-incidence X-ray diffraction measurements, these experiments, which quantify layer compositions as a function of molecular weight using changes in both scattering length density and layer thickness, extend and corroborate recent measurements on ex situ annealed samples and demonstrate that the composition profiles rapidly formed in these systems correspond to two co-existing liquid-liquid phases in thermodynamic equilibrium. The measurements also demonstrate a clear and systematic onset temperature for diffusion of the fullerenes into the PS layer that correlates with the known glass-transition temperatures of both the polymer (as a function of molecular weight) and the fullerene, revealing that the molecular mobility of the fullerenes in these systems is controlled by the intrinsic mobility of the fullerenes themselves and the ability of the polymer to plasticise the fullerenes at the interface. Over the temperature range investigated (up to 145 °C), measurements of equilibrated composition profiles as a function of temperature (during gradual cooling) reveal no significant changes in composition profile, other than those associated with the known thermal expansion/contraction of polystyrene thin-films.

Study protocol: older people in retirement villages. A survey and randomised trial of a multi-disciplinary invention designed to avoid adverse outcomes.

BACKGROUND: There is increasing interest among older people in moving into retirement villages (RVs), an attractive option for those seeking a supportive community as they age, while still maintaining independence. Currently in New Zealand there is limited knowledge of the medical, service supports, social status and needs of RV residents. The objective of this study is to explore RV facilities and services, the health and functional status of RV residents, prospectively study their healthcare trajectories and to implement a multidisciplinary team intervention to potentially decrease dependency and impact healthcare utilization. METHODS: All RVs located in two large district health boards in Auckland, New Zealand were eligible to participate. This three-year project comprised three phases: The survey phase provided a description of RVs, residents' characteristics and health and functional status. RV managers completed a survey of size, facilities and recreational and healthcare services provided in the village. Residents were surveyed to establish reasons for entry to the village and underwent a Gerontology Nurse Specialist (GNS) assessment providing details of demographics, social engagement, health and functional status. The cohort study phase examines residents' healthcare trajectories and adverse outcomes, over three years. The final phase is a randomised controlled trial of a multidisciplinary team intervention aimed to improve health outcomes for more vulnerable residents. Residents who triggered potential unmet health needs during the assessment in the survey phase were randomised to intervention or usual care groups. Multidisciplinary team meetings included the resident and support person, a geriatrician or gerontology nurse practitioner, GNS, pharmacist and General Practitioner. The primary outcome of the randomised controlled trial will be first acute hospitalization. Secondary outcomes include all acute hospitalizations, long-term care admissions, and all-cause mortality. DISCUSSION: This paper describes the study protocol of this complex study. The study aims to inform policies and practices around health care services for residents in retirement villages. The results of this trial are expected early 2020 with publication subsequently. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry: ACTRN12616000685415 . Registered 25.5.2016. Universal Trial Number (UTN): U111-1173-6083.

A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major.

OBJECTIVES: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. BACKGROUND: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. METHODS: We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. RESULTS: Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. CONCLUSIONS: Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings.

The relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity.

Background: Maternal nutrition intakes may influence neonatal birthweight and adiposity; however, inconsistencies within the literature exist. The relationships between maternal dietary intakes in early pregnancy and both birthweight and neonatal adiposity requires elucidation. This study examined the relationship between early pregnancy dietary intakes and subsequent birthweight and neonatal adiposity. Methods: Women were recruited at their convenience after sonographic confirmation of a singleton pregnancy. Women completed a Willet food frequency questionnaire evaluating habitual food and nutrient intakes at their first antenatal visit. Neonatal body composition was measured using air-displacement plethysmography. Results: Of the 385 mother-neonate dyads, mean maternal age was 30.8 ± 5.3 years, mean Body Mass Index (BMI) was 24.5 ± 4.8 kg/m2 and 41.8% (n = 161) were nulliparous. There were no relationships between maternal food intakes and birthweight (P > 0.05) (n = 385). On multivariable analysis there was a positive relationship between polyunsaturated fat and neonatal fat mass index (FMI) (beta = 0.015, 95% CI = 0.002-0.028, P = 0.04) (n = 80). Conclusion: Dietary intakes of polyunsaturated fat in early pregnancy are positively associated with neonatal FMI at birth on multivariable analysis. Further longitudinal studies need to explore this association and the long-term implications for the neonate.

Maternal Obesity and Neck Circumference.

Obese women are more likely to require general anaesthesia for an obstetric intervention than non-obese. Difficult tracheal intubation and oxygen desaturation is more common in pregnancy. Failed tracheal intubation has been associated with an increase in neck circumference (NC). We studied the relationship between maternal obesity and NC as pregnancy advanced in women attending a standard antenatal clinic. Of the 96 women recruited, 13.5% were obese. The mean NC was 36.8cm (SD 1.9) in the obese women compared with 31.5cm (SD 1.6) in women with a normal BMI (p < 0.001) at 18-22 weeks gestation. In the obese women it increased on average by 1.5cm by 36-40 weeks compared with an increase of 1.6 cm in women with a normal BMI. The antenatal measurement of NC is a simple, inexpensive tool that is potentially useful for screening obese women who may benefit from an antenatal anaesthetic assessment.

Does convenience matter in health care delivery? A systematic review of convenience-based aspects of process utility.

OBJECTIVES: To systematically review the existing literature on the value associated with convenience in health care delivery, independent of health outcomes, and to try to estimate the likely magnitude of any value found. METHODS: A systematic search was conducted for previously published studies that reported preferences for convenience-related aspects of health care delivery in a manner that was consistent with either cost-utility analysis or cost-benefit analysis. Data were analyzed in terms of the methodologies used, the aspects of convenience considered, and the values reported. RESULTS: Literature searches generated 4715 records. Following a review of abstracts or full-text articles, 27 were selected for inclusion. Twenty-six studies reported some evidence of convenience-related process utility, in the form of either a positive utility or a positive willingness to pay. The aspects of convenience valued most often were mode of administration (n = 11) and location of treatment (n = 6). The most common valuation methodology was a discrete-choice experiment containing a cost component (n = 15). CONCLUSIONS: A preference for convenience-related process utility exists, independent of health outcomes. Given the diverse methodologies used to calculate it, and the range of aspects being valued, however, it is difficult to assess how large such a preference might be, or how it may be effectively incorporated into an economic evaluation. Increased consistency in reporting these preferences is required to assess these issues more accurately.

A national survey of implementation of guidelines for gestational diabetes mellitus.

In 2010, national guidelines for the management of gestational diabetes mellitus (GDM) were published by the Health Service Executive (HSE). In 2012, a questionnaire was distributed to all maternity units to survey implementation of the guidelines. All units screened women for GDM, but used different screening tests with fifteen units (79%) using the recommended 75g OGTT, three units (16%) using a 100g OGTT and one unit (5%) using a 50g glucose challenge test. Optimal outcomes are best achieved through multidisciplinary diabetes-obstetric care and this was available in nine of the units (47%). The prevalence of GDM varied from 2.2 - 7.4%. Insulin usage varied from 15-56%. Six centres (31%) had not implemented the national guidelines in full because of lack of resources. Despite national endorsement of the guideline, significant variations remain in implementation. This may lead to differences in clinical outcomes depending on where a woman attends for obstetric care.

The use of digital media by women using the maternity services in a developed country.

The provision of high quality healthcare information about pregnancy is important to women and to healthcare professionals and it is 1 driven, in part, by a desire to improve clinical outcomes,. The objective of this study was to examine the use of digital media by women' to access pregnancy information. A questionnaire was distributed to women attending a large maternity hospital. Of the 522 respondents, the mean age was 31.8 years, 45% (235/522) were nulliparous, 62% (324/522) lived in the capital city and 29% (150/522) attended the hospital as private patients. Overall 95% (498/522) used the internet for pregnancy information, 76% (399/522) had a smartphone and 59% (235/399) of smartphone owners had used a pregnancy smartapp. The nature of internet usage for pregnancy information included discussion forums (70%), social networks (67%), video media (48%), e-books (15%), blogs (13%), microblogs (9%) and podcasts (4%). Even women who were socially disadvantaged reported high levels of digital media usage. In contemporary maternity care women use digital media extensively for pregnancy information. All maternity services should have a digital media strategy.

Physiological comparison of conditioned and non-conditioned university horses following semester break.

Periods of limited activity during semester break may reduce performance during return to ridden work. This study evaluated fitness and muscling of horses when returning to work, following a 12-week period during which horses either continued (conditioned) or discontinued (non-conditioned) ridden work. It was hypothesized that non-conditioned horses would have a lower level of fitness, resulting in higher resting and peak heart rates and lower levels of muscling. Twelve mature, stock type horses aged 16 ± 5 years were assigned to either a conditioned group that maintained light-to-moderate riding or a non-conditioned group receiving no formal exercise. All horses had access to voluntary exercise for 12-24hr/d on grass pasture (1.5-2.5 hectares). Following the 12-week period, all horses were placed into a light-to-moderate intensity exercise program with resting heart rate, peak heart rate, body condition score, gaskin and forearm circumference, and topline muscle measurements performed on d 0, 14, and 28. Peak and resting heart rates were not different between groups (P > 0.05) but increased for both groups throughout the study (P = 0.04). Gaskin circumference of non-conditioned horses was larger (P = 0.04), although non-conditioned horses tended to be heavier (551.4 versus 491.4 ± 21.4 kg; P = 0.07). Conditioned horses had greater average topline muscling scores (P = 0.02). Horses that were conditioned over a 12-week break had greater muscling, but changes in fitness were not detected. Pasture access could contribute to maintenance of fitness during unridden periods.

Ecohydrological and socioeconomic integration for the operational management of environmental flows.

Investment in and operation of flow control infrastructure such as dams, weirs, and regulators can help increase both the health of regulated river ecosystems and the social values derived from them. This requires high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information. We developed such an information base for integrated environmental flow management in the River Murray in South Australia (SA). A hydrological model was used to identify spatiotemporal inundation dynamics. River ecosystems were classified and mapped as ecohydrological units. Ecological response models were developed to link three aspects of environmental flows (flood duration, timing, and inter-flood period) to the health responses of 16 ecological components at various life stages. Potential infrastructure investments (flow control regulators and irrigation pump relocation) were located by interpreting LiDAR elevation data, digital orthophotography, and wetland mapping information; and infrastructure costs were quantified using engineering cost models. Social values were quantified at a coarse scale as total economic value based on a national survey of willingness-to-pay for four key ecological assets; and at a local scale using mapped ecosystem service values. This information was integrated using a constrained, nonlinear, mixed-integer, compromise programming optimization model and solved using a stochastic Tabu search algorithm. We tested the model uncertainty and sensitivity using 390 Monte Carlo model runs at varying weights of ecological health vs. social values. Integrating ecohydrological and socioeconomic information identified environmental flow management regimes that efficiently achieved both ecological and social objectives. Using an ecologically weighted efficient and socially weighted efficient scenario, we illustrated model outputs including a suite of cost-effective infrastructure investments and an operational plan for new and existing flow control structures including dam releases, weir height manipulation, and regulator operation on a monthly time step. Both the investments and management regimes differed substantially between the two scenarios, suggesting that the choice of weightings on ecological and social objectives is important. This demonstrates the benefit of integrating high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information for guiding the investment in and operational management of environmental flows.

Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis.

BACKGROUND: Endometriosis is a metastatic disease without obvious tumorigenesis. Expression of S100P, S100A4, osteopontin (OPN) or anterior gradient homologue 2 (AGR2) proteins can induce metastasis but fail to induce tumorigenesis per se. We now explore whether this group of metastasis-inducing proteins (MIPs) are associated with the pathogenesis of endometriosis. METHODS: Eutopic endometrial biopsies were taken from 73 women (35 fertile women without endometriosis and 38 women with surgically diagnosed endometriosis). Ectopic endometriotic lesions were collected from eight of the women with endometriosis. The expression of MIPs at the cellular level was evaluated by immunohistochemistry and the presence of these proteins in the endometrial tissues was verified by western blotting and their gene expression was confirmed by RT-PCR. RESULTS: All four MIPs were immunolocated in the endometrium of control women and S100P, AGR2 and OPN showed a cyclical variation. Proliferative phase eutopic endometrium of both groups showed a similar staining pattern for all MIPs, whereas secretory phase endometrium showed a differential expression between controls and cases. The secretory phase endometrial immunostaining of controls showed weak stromal and perivascular AGR2, and decreased stromal and glandular S100P. In contrast, immunostaining for all MIPs was increased in the late secretory endometrial samples of women with endometriosis and intense immunostaining was seen for S100A4 in the stroma (P< 0.05) and for S100P (P< 0.001) and AGR2 (P< 0.0001) in both glands and stroma (P< 0.001). All active peritoneal endometriotic lesions showed strong immunostaining for each of the MIPs studied. CONCLUSIONS: We propose that these MIPs enhance endometrial cell invasiveness and contribute to the establishment of ectopic endometriotic deposits after retrograde menstruation.

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression.

BACKGROUND: Immune checkpoint inhibition is an established treatment in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative (TN) breast cancer (BC). However, the immune landscape of breast cancer brain metastasis (BCBM) remains poorly defined. MATERIALS AND METHODS: The tumour-infiltrating lymphocytes (TILs) and the messenger RNA (mRNA) levels of 770 immune-related genes (NanoString™, nCounter™ Immuno-oncology IO360) were assessed in primary BCs and BCBMs. The prognostic role of ARG2 transcripts and protein expression in primary BCs and its association with outcome was determined. RESULTS: There was a significant reduction of TILs in the BCBMs in comparison to primary BCs. 11.5% of BCs presented a high immune infiltrate (hot), 46.2% were altered (immunosuppressed/excluded) and 34.6% were cold (no/low immune infiltrate). 3.8% of BCBMs were hot, 23.1% altered and 73.1% cold. One hundred and twelve immune-related genes including PD-L1 and CTLA4 were decreased in BCBM compared to the primary BCs (false discovery rate <0.01, log2 fold-change >1.5). These genes are involved in matrix remodelling and metastasis, cytokine-chemokine signalling, lymphoid compartment, antigen presentation and immune cell adhesion and migration. Immuno-modulators such as PD-L1 (CD274), CTLA4, TIGIT and CD276 (B7H3) were decreased in BCBMs. However, PD-L1 and CTLA4 expression was significantly higher in TN BCBMs (P = 0.01), with CTLA4 expression also high in human epidermal growth factor receptor 2-positive (P < 0.01) compared to estrogen receptor-positive BCBMs. ARG2 was one of four genes up-regulated in BCBMs. High ARG2 mRNA expression in primary BCs was associated with worse distant metastasis-free survival (P = 0.038), while ARG2 protein expression was associated with worse breast-brain metastasis-free (P = 0.027) and overall survival (P = 0.019). High transcript levels of ARG2 correlated to low levels of cytotoxic and T cells in both BC and BCBM (P < 0.01). CONCLUSION: This study highlights the immunological differences between primary BCs and BCBMs and the potential importance of ARG2 expression in T-cell depletion and clinical outcome.

Predictors of death and new disability after critical illness: a multicentre prospective cohort study.

PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.

Peralkaline volcanicity on the Eurasia Basin margin.

The Kap Washington Group of post-Palaeozoic explosive volcanic rocks was discovered in 1969 on the north coast of Greenland. Although there have been uncertainties regarding their age and chemical character, they have featured prominently in geotectonic reconstructions of the Arctic regions-in recent interpretations as products of the Yermak hot spot, generated on the Nansen spreading axis during the opening of the Eurasia Basin. We present here new evidence which confirms the volcanicity as end-Cretaceous in age and of peralkaline type. We show that a direct connection with the Yermak hot spot is improbable and infer that the volcanic rocks were generated in a continental extensional rift environment before the break-up of the Laurasian plate in the Arctic. Their age helps to constrain the timing of this poorly understood event.

Evaluation of a co-facilitated information and learning programme for service users: the EOLAS programme.

BACKGROUND: The co-production and co-facilitation of recovery-focused education programmes is one way in which service users may be meaningfully involved as partners. OBJECTIVES: To evaluate the impact of a clinician and peer co-facilitated information programme on service users' knowledge, confidence, recovery attitudes, advocacy and hope, and to explore their experience of the programme. METHODS: A sequential design was used involving a pre-post survey to assess changes in knowledge, confidence, advocacy, recovery attitudes and hope following programme participation. In addition, semi-structured interviews with programme participants were completed. Fifty-three participants completed both pre- and post-surveys and twelve individuals consented to interviews. RESULTS: The results demonstrated statistically significant changes in service users' knowledge about mental health issues, confidence and advocacy. These improvements were reflected in the themes which emerged from the interviews with participants (n = 12), who reported enhanced knowledge and awareness of distress and wellness, and a greater sense of hope. In addition, the peer influence helped to normalise experiences for participants, while the dual facilitation engendered equality of participation and increased the opportunity for meaningful collaboration between service users and practitioners. CONCLUSIONS: The evaluation highlights the potential strengths of a service user and clinician co-facilitated education programme that acknowledges and respects the difference between the knowledge gained through self-experience and the knowledge gained through formal learning.

Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.

Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.

Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain.

We cloned a novel ankyrin, Ank3, from mouse kidney cDNA. The full-length transcript is predicted to encode a 214-kD protein containing an 89 kD, NH2 terminal "repeat" domain; a 65 kD, central "spectrin-binding" domain; and a 56 kD, COOH-terminal "regulatory" domain. The Ank3 gene maps to mouse Chromosome 10, approximately 36 cM from the centromere, a locus distinct from Ank1 and Ank2. Ank3 is the major kidney ankyrin. Multiple transcripts of approximately 7.5, 6.9, 6.3, 5.7, 5.1, and 4.6 kb are highly expressed in kidney where Ank1 and Ank2 mRNAs are barely detectable. The smaller mRNAs (< or = 6.3 kb) lack the entire repeat domain. These transcripts have a unique 5'untranslated region and NH2-terminal sequence and encode a predicted protein of 121 kD. Two small sequences of 21 and 18 amino acids are alternatively spliced at the junction of the repeat and spectrin-binding domains in the larger (> or = 6.9 kb) RNAs. Alternative splicing of a 588 bp sequence (corresponding to a 21.5-kD acidic amino acid sequence) within the regulatory domain also occurs. Ank3 is much more widely expressed than previously described ankyrins. By Northern hybridization or immunocytochemistry, it is present in most epithelial cells, in neuronal axons, in muscle cells, and in megakaryocytes/platelets, macrophages, and the interstitial cells of Leydig (testis). On immunoblots, an antibody raised to a unique regions of the regulatory domain detects multiple Ank3 isoforms in the kidney (215, 200, 170, 120, 105 kD) and in other tissues. The 215/200 kD and 120/105-kD kidney proteins are close to the sizes predicted for the 7.5/6.9- and 6.3/5.7-kb RNAs (with/without the 588-bp acidic insert). Interestingly, it appears that Ank3 exhibits a polarized distribution only in tissues that express the approximately 7.0-kb isoforms, the only isoforms in the kidney that contain the repeat domain. In tissues where smaller transcripts (< or = 6.3 kb) are expressed. Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures. We conclude that Ank3 is a broadly distributed epithelial ankyrin and is the major ankyrin in the kidney and other tissues, where it plays an important role in the polarized distribution of many integral membrane proteins.