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The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2(61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R2(60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

We present the first global images of the daytime ionosphere equatorial arcs as manifested in the 83.4‐nm airglow. These images were collected by the Limb‐Imaging Ionospheric and Thermospheric Extreme‐Ultraviolet Spectrograph that commenced operations on the International Space Station in early 2017. We compare these to simultaneous images of the ionospheric radiative recombination airglow at 135.6 nm measured between 250‐ and 350‐km tangent altitudes, where the emission is generated primarily by radiative recombination of ionospheric plasma. We find that these signatures of the dense crests of the Equatorial Ionization Anomaly, their symmetry, and daily variability at 1300–1600 LT over 1–6 April 2017 do not show any strong periodicity during this time. These results are also important to the joint interpretation of these two correlated extreme and far ultraviolet emission features measured under solar minimum conditions and the evaluation of absorption and radiative transfer effects that affect these emissions differently. We have accumulated a set of new images of ultraviolet light that naturally emanates from the upper atmosphere and its embedded plasma (the ionosphere). In particular, we have imaged the pair of pervasive, dense, bands of plasma that surround Earth to the north and south of the magnetic equator. Our images were collected during the afternoon local time periods, which can expose how presunset conditions set up these bands of high plasma density to wax or wane through the postsunset hours. Changes in the density and symmetry of these bands can also be indicators of upper atmospheric winds, electric fields, and even perturbations from the lower atmosphere that propagate up through to these outer reaches of Earth's space environment. Global maps of the daytime equatorial ionization anomaly (EIA) are made using 83.4 and 135.6 nm in absorption and emission, respectivelyThe EIA from 1300 to 1600 LT in April 2017 does not show evidence of longitudinal variability indicative of a wave 4 structureObserved north‐south asymmetry suggests meridional winds, with 135.6 nm more sensitive to changes than 83.4 nm from the low‐altitude vantage

Execute jobs worth $1 million or less with efficiency and cost/schedule control Worldwide, the petroleum and chemical industry spends billions each year to maintain existing manufacturing facilities. Except for routine [...]

PURPOSE: Many occupations require employees to work with hands overhead for sustained periods. Prolonged arm elevation decreases brachial artery blood pressure and is considered to directly contribute to temporary ischemic conditions in the wrist and hand. The effects of overhead tasks on upper extremity work-related musculoskeletal disorders, including carpal tunnel syndrome, are unclear. However, overhead work greater than two hours per day has been shown to significantly predict carpal tunnel syndrome in the construction trades. The purpose of this study was to measure and compare effects of arm elevation on finger blood pressure and skin temperature. SUBJECTS: Twenty-five female and fifteen male subjects without prior history of upper extremity work-related musculoskeletal disorders consented to participate in this study. METHODS AND MATERIALS: Finger blood pressure was measured in both the right and left third digit using an automated finger blood pressure monitor. Simultaneously, skin temperature was measured on the palmer surface of the second distal phalanx on both hands. Two measurements were taken at each of three positions of shoulder scaption (90 [degrees], 120 [degrees], 150 [degrees]) and at initial and final resting positions (0 [degrees] shoulder scaption) for each subject. ANALYSES: One-way fixed-effect analysis of variance with repeated measures was performed, with post hoc pairwise comparisons using Tukey's Standardized Range Test. RESULTS: Significant (p [is less than] 0.05) decreases in systolic and diastolic long finger blood pressures were found at each increasing elevation of the arm. No changes existed on contralateral side. No changes were found in skin temperature or pulse rate. CONCLUSION: The results of this study indicate that positioning the hand overhead is associated with ipsilateral decreased finger blood pressure. These results may be an important initial step in understanding wrist and hand work-related musculoskeletal disorders for individuals working with arms in hand-overhead positions., Cook T, Craft W, Meyer S, Harper D, Shibley L; Physical Therapy Graduate Program, The University of Iowa, Iowa City, IA, [...]

PURPOSE: Changes in the U.S. health care system have broadened the physical therapist's role in the treatment and prevention of occupational injuries and illnesses. The purpose of this presentation is to illustrate the physical therapist's role as facilitator in the integration of ergonomics within the business model of a manufacturing facility. DESCRIPTION: This case study involved a manufacturing and assembly plant that employs 500 workers and is one of over thirty facilities of a worldwide manufacturing company. Over a one-year period, physical therapists facilitated the development and refinement of an ergonomics continuous improvement model based on the company's four key business drivers: product quality, costs, delivery, and quality of work life. Separate "Councils" continually focused on each of the business drivers and were overseen by a Customer Satisfaction Council, whose responsibilities included strategic planning, business planning, capital planning, and profit planning. The Councils, through monthly meetings, monitored clearly defined outcomes and identified continuous improvement opportunities. Physical therapists ,were involved in the Council's decision-making process regarding ergonomic and safety issues and facilitated ergonomic project team meetings that involved line workers and managers. Physical therapists served as a critical link between the decision-makers in the councils and the employees working on the line. Integrating the ergonomics process into the company's key business drivers helped ensure that ergonomics became part of the manufacturing operations rather than another "program of the month." OBSERVATIONS: Although, integration of the ergonomics process in this plant is continuing to be evaluated, the key business outcomes related to product quality, costs, delivery, and quality of work life all indicate positive results. Interestingly, the business driver that has been most responsive to the ergonomics program has been product quality. This is not surprising since most of the initial workplace modifications that were implemented by the ergonomics teams relate to materials handling. With the reduction in operator fatigue that accompanied improved materials handling, fewer parts were mishandled, dropped, damaged, or poorly manufactured or incorrectly assembled. Gains in quality and productivity have reduced the need for overtime and the associated risks of further injury. CONCLUSIONS: In addition to reducing the risk of occupational injury and illness, physical therapists can contribute to the successful integration of ergonomics into a company's business plan. Good ergonomics is good economics., Rosecrance J, Cook T; Physical Therapy Graduate Program, The University of Iowa, Iowa City, IA, [...]

There are limited qualitative data describing patients’ experience of the symptoms and impacts of refractory chronic cough (RCC) or unexplained chronic cough (UCC). Objectives of this study were to determine patients’ perceptions of the key symptoms and impacts of RCC and UCC on well-being, health-related quality of life, work productivity, and social relationships. Additionally, patients’ perception of meaningful treatment benefit was explored.

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

The latest early Campanian archipelago deposits of the Kristianstad Basin, southern Sweden, yield one of the most diverse Cretaceous chondrichthyan faunas collected from a narrow stratigraphical interval. Building on previous descriptions of various selachians, squatiniform and synechodontiform sharks are added to the faunal list. Squatinidae is represented by Squatina(Squatina) lundegrenisp. nov. and Squatina(Squatina) fortemordeosp. nov. The poorly preserved type specimens of the nominal Squatina hasseifrom the Maastrichtian of The Netherlands were recently regarded conspecific with better preserved Santonian–Maastrichtian teeth of Squatina(Cretascyllium) from the Anglo-Paris Basin. This appears to have been based largely on the assumption that the nominal S. hasseiwas the only Squatinapresent in NW Europe during the Santonian–Maastrichtian. The Swedish material indicates a greater diversity of squatinoids, and the nominal S. hasseiis here regarded as a nomen dubiumof uncertain subgeneric affinity. Two types of synechodontid teeth with a tall central cusp co-occur in the Campanian of the Kristianstad Basin. Based on articulated jaws of the markedly dignathic S. dubrisiensisfrom the Cenomanian of England, the two morphs are regarded as upper and lower anterior teeth of the single species S. filipisp. nov.

Hypotensive anesthesia is routinely used during craniosynostosis corrections to reduce blood loss. Noting that cerebral oxygenation levels often fell below recommended levels, the authors sought to measure the effects of hypotensive versus standard anesthesia on blood transfusion rates.

Some scientists consider the loss of the American chestnut from forests in the eastern United States as one of the greatest forest ecological disasters in the 20th century. The American Chestnut Foundation has been attempting to restore chestnut by backcrossing blight‐resistant Chinese chestnut to American chestnut and selecting those strains with blight resistance. Third‐generation backcross seeds and seedlings have been produced and planted by researchers. Surface‐mined lands provide a land base where these backcross chestnut seedlings may be introduced back into forests. In 2008, seeds of two parent species of chestnut (100% American and 100% Chinese) and three breeding generations (B1F3, B2F3, and B3F2backcrosses) were planted into loosely graded mine soils with and without tree shelters. First‐year establishment from seeds averaged 81%. After the fourth year, survival without shelters declined for all chestnut stock types except for Chinese (80%): American 40%, B1F370%, B2F340%, and B3F255%. Survival with shelters was only slightly better after the fourth year (average, 60% with shelters and 57% without). Height growth was not different among stock types, and average height after the fourth year was 43 cm without shelters and 56 cm with shelters. In 2009, seeds and seedlings of the same chestnut stock types were planted into brown (pH 4.5) or gray (pH 6.6) mine soils. Only six out of 250 seeds germinated, which was very poor considering 81% average seed germination in 2008. Transplanted chestnut seedling survival was much better. After the third year, seedling survival was 85% in brown and 80% in gray soil, but significant differences were found with stock types. Survival was significantly higher with American, Chinese, and B1F3stock types (75%) than with B2F3and B3F2(60%). Height after the third season averaged 90 cm on brown and 62 cm on gray soil. Chestnut backcrosses displayed no hybrid vigor and were not better in survival and growth than the parent stock. All five stock types grew on mine soils in West Virginia, and we found surface mines to be promising sites for introducing blight‐resistant chestnut backcross trees into the Appalachian forest.

One of the oldest visual illusions consists of observers' tendency to estimate vertical lines as longer than equal horizontal lines. This Horizontal-Vertical Illusion has been studied widely; however, most studies may not generalize to natural contexts because they have not addressed the low-level processes that occur rapidly and in response to context-free lines vs the possibility for high-level processes that arise over time in response to context. These issues were investigated via a novel design: rapid time-sequencing embedded within the context of natural images. Participants saw different levels of context and the Horizontal-Vertical Illusion was measured. In traditional Horizontal-Vertical Illusion displays without natural context, there was a robust invariance of the illusion to stimulus duration. Within context, however, there was strong modulation: the magnitude of the illusion decreased by over 50% or increased over 30%, depending upon placement within context. Knowledge of object properties such as size or line length did not account for this effect. It appears that previous domain-general investigations of the Horizontal-Vertical Illusion did not address the specific higher-order processes that produce the illusion in natural contexts.

The article offers information on the strike held by the Writers Guild of America against the Alliance of Motion Picture and Television Producers. It notes that the Guild voted to strike on March 6, 1988. The strike option was voted by 94% of the members. The author states that this 22-week strike is the longest in the Guild's history.

Histopathology provides the gold standard assessment of colonoscopic biopsies. Infrared spectroscopy can potentially map biochemical changes across a tissue section identifying disease. The purpose of this study was to determine if infrared spectroscopy could classify different colorectal pathologies and to investigate biochemical composition. Colonoscopic tissue biopsies were snap frozen at colonoscopy. 10 micron thick sections were mounted on CaF2slides. 3- D spectral datasets (2 spatial dimensions and one spectral) were measured from thawed specimens using a Perkin Elmer infrared imaging system in transmission mode. Contiguous tissue sections stained with H&E were reviewed by a specialist gastrointestinal pathologist for comparison. Tissue spectra from epithelial tissues were classified using principal components fed linear discriminant analysis with leave one out cross validation. Reference spectra from purchased biochemicals (Sigma-Aldrich) were measured. Ordinary least squares analysis estimated the relative biochemical signal contribution from epithelial regions. Spectra from tissue epithelia measured from normal tissue, hyperplastic polyps, adenomatous polyps, cancer and ulcerative colitis samples were classified with accuracies in excess of 90%. Ordinary least squares analysis demonstrated a higher DNA to cytoplasm ratio in cancer compared to normal tissue. FTIR spectra from epithelia can be used to classify colorectal pathologies with high accuracy. Ordinary least squares analysis shows promise for extraction of useful biochemical information. These techniques could aid the histopathologist and ultimately lead to automated histopathological processing.

With the current emphasis on healthcare reform and cost effectiveness, methods to increase healthcare efficiency while improving outcomes are paramount. With reference to breast cancer, delay in diagnosis can cause significant morbidity and mortality, as well as increased long term health care costs. Assessment with short interval mammographic follow-up of BI-RADS category 3 lesions has been shown to increase detection of a small number of breast cancers at an early stage. Because of the importance of timely follow-up for these patients, we propose a novel computer application that identifies patients due for short-term mammographic follow-up, thus reducing costly hours spent by personnel, reducing human error, and improving patient compliance. Our web-based application mines radiology reports and scheduling information to generate lists of patients due for short-term mammographic follow-up of BI-RADS category 3 results. The results can be placed in a worklist that can be used by a staff member to contact patients to schedule follow-up appointments. Additional analytic features of the application can identify referral characteristics that may serve as potential sources for improvement of patient follow-up. We believe that an automated system can be designed to improve patient care and compliance with follow-up of BI-RADS category 3 results.

Many anaesthetists have found the size 1.5 classic Laryngeal Mask Airway unsuitable for use in children under 10 kg, whereas recent studies evaluating the ProSeal Laryngeal Mask Airway (PLMA) show high success rates, even during laparoscopic surgery. Our routine practice has been to use tracheal intubation for inguinal herniotomy in children weighing less than 10 kg. Following the introduction of the PLMA to our hospital, we decided to audit our use of the PLMA 1.5 in this group of patients.We included 20 consecutive infants, aged less than six months and weighing 5 to 10 kg. We recorded patient, anaesthetic and insertion details, device performance data and complications. No aspect of anaesthetic practice was changed by involvement in this audit.The PLMA was inserted successfully at the first attempt in 85% (17/20) of infants. Overall successful insertion occurred in 90% (18/20) and satisfactory airway maintenance was provided for the duration of anaesthesia in 90% (18/20). The mean leak pressure was 24 cmH20) (range 15 to 30 cmH20).We found the 1.5 PLMA provided a satisfactory airway in 90% of infants. This report adds to the evidence that the PLMA 1.5 can provide a satisfactory alternative to intubation in selected infants.

The article reports on the strike of the Writers Guild of America (WGA) against the Alliance of Motion Picture and Television Producers on March 6, 1988 in the U.S. The strike focused on the call of screenwriters to get paid for the reuse of their works especially with the development of videotape cassettes. According to the author, the strike showed how the WGA is committed to take a strike to resolve problems and do what is necessary.

This article first appeared in Bedsore Biomechanicsand is reproduced by kind permission of Palgrave Macmillan, Macmillan Publishers Ltd

Targeting gene therapy vectors to the fetal intestinal tract could provide a novel means toward prevention of the early postnatal intestinal pathology of cystic fibrosis and other conditions, such as congenital enteropathy, that cause intestinal failure. Among these conditions, cystic fibrosis is by far the most common lethal genetic disease. It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus. Prenatal treatment of genetic disease may avoid early-onset tissue damage and immune sensitization, and may target cells that are less accessible in the adult. We investigated gene transfer to the fetal gut, using a minimally invasive injection technique. First-generation replication-deficient adenoviral vectors encoding the β-galactosidase gene and transduction-enhancing agents were injected into the stomach of early-gestation fetal sheep (n = 8, 60 days of gestation; term, 145 days) under ultrasound guidance. Reporter gene expression was observed 2 days after injection in the villi of the gastrointestinal epithelia after 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside staining and β-galactosidase immunohistochemistry of fetal tissues. Expression of β-galactosidase, as measured by enzyme-linked immunosorbent assay, was enhanced after pretreatment of the fetal gut with sodium caprate, which opens tight junctions, and after adenovirus complexation with DEAE-dextran, which confers a positive charge to the virus. Instillation of the fluorocarbon perflubron after virus delivery resulted in tissue transduction from the fetal stomach to the colon. Using a clinically relevant technique, we have demonstrated widespread gene transfer to the fetal gastrointestinal epithelia.

Cyclooxygenase (COX) catalyzes the rate-limiting step in the conversion of essential fatty acids (EFAs) to bioactive molecules such as prostaglandins (PGs), which play critical roles in many aspects of female reproduction and in fetal development. There are two primary related COX isoforms, the constitutively expressed COX-1 and the inducible COX-2. Although the expression of COX-1 and COX-2 has been demonstrated in the amnion, chorion, and decidua, relatively little information exists with regard to their expression and physiological function in the placenta during gestation. In this study, we have elucidated the spatial and temporal patterns of COX-1 and COX-2 expression in the labyrinthine and junctional zones of the developing rat placenta, in the human term placenta, and in the BeWo human trophoblast model using semiquantitative RT-PCR, Western blot, and immunohistochemical analyses. The mRNA and protein expression of COX-1 and COX-2 were demonstrated in the developing rat placenta with increasing expression observed toward parturition. COX-2 exhibited greater expression than COX-1 after mid-gestation and had a corresponding shift in spatial expression from the labyrinthine to the junctional zone at term. COX-1 and -2 were also expressed in human term placenta, while BeWo cells exhibited moderate expression of COX-1 and weak expression of COX-2. The results demonstrate that COX-1 and COX-2 are expressed in the rat and human placentas. The differential expression patterns in the rat placenta, especially of COX-2, imply that there may be gestational changes in the biosynthesis of PGs and other potential bioactive EFA metabolites. Establishing the expression of the COX isoforms provides a framework for future investigations into the functional and physiological significance of COX-1 and COX-2 in the placenta, particularly with respect to influencing normal pregnancy and fetal development, and to provide insights into therapeutic utilization of COX inhibitors in pregnancy. Keywords: Cyclooxygenase; placenta; trophoblast; pregnancy; metabolism; rat; human

To investigate the association between Alzheimer disease (AD) and worker functions and traits associated with occupations.

Presents excerpts from the script of the unproduced television program "Eight Days at Remolino," teleplay by T.S. Cook, story by T.S. Cook and Robert Eisele.

The Laryngeal Tube (LT) performs similarly to the classic laryngeal mask airway during controlled ventilation but with an improved airway seal. We compared the laryngeal tube with the ProSeal laryngeal mask airway (PLMA) throughout anaesthesia.

We compared the modified Airway Management Device (AMD) with the classic Laryngeal Mask Airway (cLMA) in a randomized comparative trial.

Only a prototype laryngeal tube has been compared with the classic LMA for brief periods of anaesthesia. We compared the new laryngeal tube (which had several improvements in design) with the classic LMA.

Single-use laryngoscopes are becoming used more widely.

The ProSeal is a wire-reinforced laryngeal mask airway with an additional drain tube that leads to the distal tip of the laryngeal cuff. The design should improve the seal with the larynx.

In order to establish whether extra-renal cells contribute to the turnover and repair of renal tissues, this study examined kidneys of female mice that had received a male bone marrow transplant and kidney biopsies from male patients who had received kidney transplants from female donors. By using in situ hybridization to detect Y-chromosomes it could be demonstrated that circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells. In the human renal grafts it was confirmed that some of the recipient-derived cells within the kidney exhibited a tubular epithelial phenotype, by combining in situ hybridization with immunostaining for the epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients of male bone marrow grafts showed co-localization of Y-chromosomes and tubular epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing cells were observed within glomeruli, with morphology and location appropriate for podocytes. Within the murine kidney, these Y-chromosome-positive cells were negative for the mouse macrophage marker F4/80 antigen and leukocyte common antigen, but were vimentin-positive. The presence of bone marrow-derived cells was noted in both histologically normal mouse kidneys and in human transplanted kidneys suffering damage from a variety of causes. These data indicate that bone marrow cells contribute to both normal turnover of renal epithelia and regeneration after damage, and it is suggested that this could be exploited therapeutically. Copyright © 2001 John Wiley & Sons, Ltd.

There is a high incidence of end‐stage renal failure (ESRF) of undetermined cause in the Indo‐Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo‐Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo‐Asians and Caucasians. Requirement for renal replacement therapy in Indo‐Asians presenting to our centre from Brent and Harrow was 221/106/year; no underlying diagnosis was identified in 77/106/year. Renal biopsy rate in these patients was 456/106/year, and the diagnostic categories significantly over‐represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non‐specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/106/year in Indo‐Asians and 31/106/year in Caucasians. ESRF of undetermined cause is common in UK Indo‐Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over‐represented in the Indo‐Asian population, and should be targeted for early diagnosis and treatment in this group.

In 1995–96, a survey of soil samples from subterranean clover (Trifolium subterraneum L.) paddocks was conducted across Victoria, South Australia, New South Wales and Western Australia, to determine the distribution and the prevalence of races of Phytophthora clandestina (as determined by the development of root rot on differential cultivars), and the association of its occurrence with paddock variables. In all states, there was a weak but significant association between P. clandestina detected in soil samples and subsequent root rot susceptibility of differential cultivars grown in these soil samples. Phytophthora clandestina was found in 38% of the sampled sites, with a significantly lower prevalence in South Australia (27%). There were significant positive associations between P. clandestina detection and increased soil salinity (Western Australia), early growth stages of subterranean clover (Victoria), mature subterranean clover (South Australia), recently sown subterranean clover (South Australia), paddocks with higher subterranean clover content (Victoria), where herbicides were not applied (South Australia), irrigation (New South Wales and Victoria), cattle grazing (South Australia and Victoria), early sampling dates (Victoria and New South Wales), sampling shortly after the autumn break or first irrigation (Victoria), shorter soil storage time (Victoria) and farmer’s perception of root rot being present (Victoria and New South Wales). Only 29% of P. clandestina isolates could be classified under the 5 known races. Some of the unknown races were virulent on cv. Seaton Park LF (most resistant) and others were avirulent on cv. Woogenellup (most susceptible). Race 1 was significantly less prevalent in South Australia than Victoria and race 0 was significantly less prevalent in New South Wales than in South Australia and Western Australia. This study revealed extremely wide variation in the virulence of P. clandestina. The potential importance of the results on programs to breed for resistance to root rot are discussed. in South Australia.

Fetal gene therapy has the potential to treat inherited genetic diseases in utero before significant organ damage has occurred. Rapidly expanding stem cell populations may be targeted and the introduction of transgenes to the fetus during development of the immune system could result in immune tolerance and facilitate repeat treatment postnatally. Genetic diseases such as cystic fibrosis, which are life-threatening and for which there are no currently acceptable treatments available, are suggested targets for this therapy.Ultrasound may be a safe method of delivering a therapeutic gene into the fetus, although most studies have used more invasive techniques, even in large animal models. Viral vectors currently offer the most potential. Adenovirus-based vectors are stable, independent of host cell replication, efficient at tissue infection and have been used as a 'pathfinder' to test routes of administration. Unfortunately, they are also highly immunogenic and other systems based on retrovirus or adeno-associated virus may offer advantages because of their lower immunogenicity and potential for permanent transgene expression.Our group is developing the fetal sheep model for the investigation of ultrasound-guided gene therapy in utero. This model is suitable since the sheep fetus is tolerant to manipulations, has a consistent gestation period and shows many similarities with human pregnancy. We have demonstrated significant transfection of the fetal liver and adrenal cortex after ultrasound-guided percutaneous injection of the umbilical vein with adenoviral vectors in the late gestation sheep. We are investigating and here discuss alternative routes of administration to target the fetus in early gestation via ultrasound-guided minimally invasive techniques.

Sp1-like transcription factors are characterized by three highly homologous C-terminal zinc finger motifs that bind GC-rich sequences. These proteins behave as either activators or repressors and have begun to be classified into different subfamilies based upon the presence of conserved motifs outside the zinc finger domain. This classification predicts that different Sp1-like subfamilies share certain functional properties. TIEG1 and TIEG2 constitute a new subfamily of transforming growth factor-beta-inducible Sp1-like proteins whose zinc finger motifs also bind GC-rich sequences. However, regions outside of the DNA-binding domain that differ in structure from other Sp1-like family members remain poorly characterized. Here, we have used extensive mutagenesis and GAL4-based transcriptional assays to identify three repression domains within TIEG1 and TIEG2 that we call R1, R2, and R3. R1 is 10 amino acids, R2 is 12 amino acids, and R3 is approximately 80 amino acids long. None of these domains share homology with previously described transcriptional regulatory motifs, but they share strong sequence homology and are functionally conserved between TIEG1 and TIEG2. Together, these data demonstrate that TIEG proteins are capable of repressing transcription, define domains critical for this function, and further support the idea that different subfamilies of Sp1-like proteins have evolved to mediate distinct transcriptional functions.

Sp1-like zinc finger transcription factors are involved in the regulation of cell growth and differentiation. Recent evidence demonstrating that mammalian cells express novel, yet uncharacterized, Sp1-like proteins has stimulated a search for new members of this family. We and others have recently reported that the transforming growth factor (TGF)-beta-regulated gene TIEG encodes a new Sp1-like protein that inhibits cell growth in cultured cells. Here we report the identification, nuclear localization, DNA binding activity, transcriptional repression activity, and growth inhibitory effects of TIEG2, a novel TGF-beta-inducible gene related to TIEG. TIEG2 is ubiquitously expressed in human tissues, with an enrichment in pancreas and muscle. TIEG2 shares 91% homology with TIEG1 within the zinc finger region and 44% homology within the N terminus. Biochemical characterization reveals that TIEG2 is a nuclear protein, which, as predicted from the primary structure, specifically binds to an Sp1-like DNA sequence in vitro and can repress a promoter containing Sp1-like binding sites in transfected Chinese hamster ovary epithelial cells. Furthermore, functional studies using [3H]thymidine uptake and MTS (3-(4, 3-dimethyltiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-su lfophenyl)-2 H-tetrazolium) assays demonstrate that the overexpression of TIEG2 in Chinese hamster ovary cells inhibits cell proliferation. Thus, TIEG2, together with TIEG1, defines a new subfamily of TGF-beta-inducible Sp1-like proteins involved in the regulation of cell growth.

The binding of cGMP to the noncatalytic sites on two isoforms of the phosphodiesterase (PDE) from mammalian rod outer segments has been characterized to evaluate their role in regulating PDE during phototransduction. Nonactivated, membrane-associated PDE (PDE-M, alpha beta gamma2) has one exchangeable site for cGMP binding; endogenous cGMP remains nonexchangeable at the second site. Non-activated, soluble PDE (PDE-S, alpha beta gamma2 delta) can release and bind cGMP at both noncatalytic sites; the delta subunit is likely responsible for this difference in cGMP exchange rates. Removal of the delta and/or gamma subunits yields a catalytic alphabeta dimer with identical catalytic and binding properties for both PDE-M and PDE-S as follows: high affinity cGMP binding is abolished at one site (KD >1 microM); cGMP binding affinity at the second site (KD approximately 60 nM) is reduced 3-4-fold compared with the nonactivated enzyme; the kinetics of cGMP exchange to activated PDE-M and PDE-S are accelerated to similar extents. The properties of nonactivated PDE can be restored upon addition of gamma subunit. Occupancy of the noncatalytic sites by cGMP may modulate the interaction of the gamma subunit with the alphabeta dimer and thereby regulate cytoplasmic cGMP concentration and the lifetime of activated PDE during visual transduction in photoreceptor cells.

Modeling and forecasting short-term household population growth and location is important to many organizations. Household population is forecast for the Portland SMSA. A model is developed that uses both time series and cross-sectional data. Forecasts are allocated to planning divisions within the Standard Metropolitan Statistical Area (SMSA) by univariate stochastic models.

The growth of very small fatigue microcracks was studied in a powder metallurgy nickel-base superalloy. A novel specimen containing a small crack was used, with crack growth rates being measured optically at high magnification. Interaction between the crack and the material microstructure was observed in a cyclic loading stage within a scanning electron microscope.