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(Abstracted from BJOG2022;129:597–606)Approximately 10% to 15% of monochorionic diamniotic twin pregnancies are affected by twin-to-twin transfusion syndrome (TTTS). Fetoscopic laser surgery is recognized as the standard for treating such pregnancies.

Sulfate is a potential pollutant and important nutrient linked with the nitrogen, carbon, and phosphorus cycles. The importance of different anthropogenic sulfate sources in suburban streams (septic systems, fertilizer, road salt, and infrastructure) is uncertain, and the temporal dynamics of stream export sparsely documented. We study sources and export dynamics of sulfate in suburban and forested headwater catchments. Stream baseflow discharge and sulfate concentrations were strongly positively correlated in both watersheds with the highest values in spring. Suburban concentrations and fluxes (2.48–7.5 mg/L or 25.8–78.1 μM, 16.6 kg/ha/yr) were consistently higher than forested (0.56–2.78 mg/L or 5.8–28.9 μM, 5 kg/ha/yr). Following precipitation, sulfate concentrations in both forested and suburban streams increased to concentrations above pre‐storm values and remained high after peak discharge. These dynamics suggest that both catchments have a large pool of sulfate that can be mobilized under wet conditions. Ridge‐top forest soil samples contained 210 kg/ha stored, extractable sulfate. Current atmospheric sulfate deposition rates (5–7 kg/ha/yr) are approximately in balance with sulfate export in the forested stream. In the suburban watershed, we estimated septic fields contribute up to 11 kg/ha/yr (about half from surfactants) and lawn care up to 4.3 kg/ha/yr and are the most likely sources of elevated stream sulfate. Sulfate sulfur (4.9–5.8‰ forested; 6.1–7.0‰ suburban) and oxygen isotope values (0.7–2.0‰ forested; −0.1–4.1‰ suburban) are consistent with this interpretation, but do not provide strong corroboration due to large variation and overlap in estimated source values. Sulfate can be a nutrient or pollutant that alters stream biogeochemistry depending on dissolved concentrations. For decades, atmospheric sulfur deposition was elevated due to regional anthropogenic emissions. Regulation in the 1990s resulted in decreasing deposition and increasing importance of other sulfur sources, for example, associated with land use. We studied suburban sulfate sources, including infrastructure and activities not widely recognized as sources of stream sulfate. We measured dissolved sulfate concentrations and sulfate tracer isotopes in neighboring forested and suburban watersheds. Sulfate inputs and exports are compared with budgets of possible sulfate contributions to the stream from septic systems, lawn care, road salt, building materials, and historic agriculture. The suburban stream exports about 3x more sulfate a year from the watershed than the forested stream. Extra suburban stream sulfate appears to be largely caused by human waste and cleaning products flowing to septic fields and lawn care. More sulfate is transported to the stream during the wetter spring and after rain. This elevated transport may be because the groundwater table moves upwards during wetter times and transports sulfate that was stored in soil to the stream. Identifying suburban sources of sulfate pollution is important to protecting stream health. The suburban stream has elevated sulfate concentrations and fluxes, likely due to contributions from septic systems and lawn careSulfate mobilized in seasonal‐ and event‐scale wet conditions in both forested and suburban streamsSulfate in the suburban stream is associated with soil storage mobilized in wet conditions, not runoff from impervious surfaces The suburban stream has elevated sulfate concentrations and fluxes, likely due to contributions from septic systems and lawn care Sulfate mobilized in seasonal‐ and event‐scale wet conditions in both forested and suburban streams Sulfate in the suburban stream is associated with soil storage mobilized in wet conditions, not runoff from impervious surfaces

A storage‐discharge relation tells us how discharge will change when new water enters a hydrologic system but not which water is released. Does an incremental increase in discharge come from faster turnover of older water already in storage? Or are the recent inputs rapidly delivered to the outlet, “short‐circuiting” the bulk of the system? Here I demonstrate that the concepts of storage‐discharge relationships and transit time distributions can be unified into a single relationship that can usefully address these questions: the age‐ranked storage‐discharge relation. This relationship captures how changes in total discharge arise from changes in the turnover rate of younger and older water in storage and provides a window into both the celerity and velocity of water in a catchment. This leads naturally to a distinction between cases where an increase in total discharge is accompanied by an increase (old water acceleration), no change (old water steadiness), or a decrease in the rate of discharge of older water in storage (old water suppression). The simple theoretical case of a power law age‐ranked storage‐discharge relations is explored to illustrate these cases. Example applications to data suggest that the apparent presence of old water acceleration or suppression is sensitive to the functional form chosen to fit to the data, making it difficult to draw decisive conclusions. This suggests new methods are needed that do not require a functional form to be chosen and provide age‐dependent uncertainty bounds. Storage‐discharge relations and transit time distributions are unified in a single relationship capturing both celerity and velocity effectsEmpirical data and theory suggest old water release may be accelerated or suppressed at high discharge or catchments wetnessRobust inferences about oldest water turnover require new approaches to functional estimation with age‐dependent uncertainty

The lunar history of water deposition, loss, and transport postaccretion has become an important consideration in relation to the possibility of a human outpost on the Moon. Very recent work has shown that a secondary primordial atmosphere of up to 10 mbar could have been emplaced ∼3.5×109years ago due to volcanic outgassing from the maria. Using a zero‐dimensional chemistry model, we demonstrate the temperature dependence of the resulting major atmospheric components (CO or CO2). We use a three‐dimensional general circulation model to test the viability of such an atmosphere and derive its climatological characteristics. Based on these results, we then conjecture on its capability to transport volatiles outgassed from the maria to the permanently shadowed regions at the poles. Our preliminary results demonstrate that atmospheres as low as 1 mbar are viable and that permanent cold trapping of volatiles is only possible at the poles. We confirm the viability of transient maria outgassed atmosphere for pressures from 1 to 10 mbarThree‐dimensional simulations demonstrate where volatile deposition may occurAtmospheric escape and outgassing chemistry play important roles

The models of stream reach hyporheic exchange that are typically used to interpret tracer data assume steady‐flow conditions and impose further assumptions about transport processes on the interpretation of the data. Here we show how rank Storage Selection (rSAS) functions can be used to extract “process‐agnostic” information from tracer breakthrough curves about the time‐varying turnover of reach storage. A sequence of seven slug injections was introduced to a small stream at base flow over the course of a diel fluctuation in stream discharge, providing breakthrough curves at discharges ranging from 0.7 to 1.2 L/s. Shifted gamma distributions, each with three parameters varying stepwise in time, were used to model the rSAS function and calibrated to reproduce each breakthrough curve with Nash‐Sutcliffe efficiencies in excess of 0.99. Variations in the fitted parameters over time suggested that storage within the reach does not uniformly increase its turnover rate when discharge increases. Rather, changes in transit time are driven by both changes in the average rate of turnover (external variability) and changes in the relative rate that younger and older water contribute to discharge (internal variability). Specifically, at higher discharge, the turnover rate increased for the youngest part of the storage (corresponding to approximately 5 times the volume of the channel), while discharge from the older part of the storage remained steady, or declined slightly. The method is shown to be extensible as a new approach to modeling reach‐scale solute transport that accounts for the time‐varying, discharge‐dependent turnover of reach storage. Seven tracer injections over 28 h analyzed using rank Storage Selection function theory of time‐varying transit time distributionsrSAS results show fluctuations in turnover rate of reach storage at base flow limited to a volume 5 times larger than visible channelMethod suggests an approach to parsimonious reach‐scale solute transport that accounts for time‐varying stream‐hyporheic exchange dynamics

Weathering processes weaken and break apart rock, freeing nutrients and enhancing permeability through the subsurface. To better understand these processes, it is useful to constrain physical properties of materials derived from weathering within the critical zone. Foliated rocks exhibit permeability, strength and seismic anisotropy–the former two bear hydrological and geomorphological consequences while the latter is geophysically quantifiable. Each of these types of anisotropy are related to rock fabric (fractures and foliation); thus, characterizing weathering‐dependent changes in rock fabric with depth may have a range of implications (e.g., landslide susceptibility, groundwater modeling, and landscape evolution). To better understand how weathering effects rock fabric, we quantify seismic anisotropy in saprolite and weathered bedrock within two catchments underlain by the Precambrian Loch Raven schist, located in Oregon Ridge Park, MD. Using circular geophone arrays and perpendicular seismic refraction profiles, anisotropy versus depth functions are created for material 0–25 m below ground surface (bgs). We find that anisotropy is relatively low (0%–15%) in the deepest material sampled (12–25 m bgs) but becomes more pronounced (29%–33%) at depths corresponding with saprolite and highly weathered bedrock (5–12 m bgs). At shallow soil depths (0–5 m bgs), material is seismically isotropic, indicating that mixing processes have destroyed parent fabric. Therefore, in situ weathering and anisotropy appear to be correlated, suggesting that in‐place weathering amplifies the intrinsic anisotropy of bedrock. The critical zone encompasses Earth's terrestrial surface where rock, water, soil, and biota interact to support life. Within the deeper reaches of the critical zone, rocks are subjected to weathering that transforms chemical and physical properties over time. As rocks weather, essential nutrients are released for use by organisms and space is opened within the rock allowing for water flow and storage. This study investigates how weathering and rock fabric interact. The term “rock fabric” refers to preexisting fractures and/or how minerals are organized within a rock. Schists, the rock type in this study, have a fabric with minerals made up of thin sheets, similar to a deck of cards. We examine how this rock fabric has been changed due to weathering by measuring the speed of sound waves that travel at different angles through weathered material close to the surface. Our data show that the fabric remains throughout much of the weathered material and may even become more pronounced as a result of weathering. Thus, the spacing between “cards” or the width of the fractures increases as rock is progressively weathered toward Earth's surface. Seismic surveys of weathered material in the critical zone record magnitudes of seismic anisotropy as high as 36% and that vary with depthThe fast direction of wave propagation in weathered materials aligns with the strike of foliation and fracture planes present in bedrockIn situ weathering processes likely enhance the anisotropy already present in bedrock as it is exhumed toward the surface Seismic surveys of weathered material in the critical zone record magnitudes of seismic anisotropy as high as 36% and that vary with depth The fast direction of wave propagation in weathered materials aligns with the strike of foliation and fracture planes present in bedrock In situ weathering processes likely enhance the anisotropy already present in bedrock as it is exhumed toward the surface

Aim: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. Methods: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). Results: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal serum α-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four (6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified (37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalence during the summer and late winter. Conclusion: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism, significance and effects of this asymptomatic viral presence require further study.

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy‐Walker malformation on ultrasound examination. Autopsy showed low‐set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy‐Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable.

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified. Copyright © 2002 John Wiley & Sons, Ltd.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentred (12) prospective, randomized trial comparing continuous ultrasound‐guided early amniocentesis (EA) and mid‐trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures ‘judged to be difficult’ by the operator, and post‐procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11.1 per cent, compared with non‐hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first‐trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype. Copyright © 1999 John Wiley & Sons, Ltd.

The calculation of incidence rates of melanoma in New Zealand has been hampered in the past by incomplete registration of cases. The aim of this study was to document the incidence of melanoma in the Auckland Caucasian population and to define the pathologic characteristics of these lesions. Data were collected for the Auckland region from the New Zealand Cancer Registry and the Auckland Melanoma Unit database for 1995 and combined with census statistics to give the crude and age-standardized rates for invasive melanoma. The results were analyzed by gender, morphology, body site, and thickness. The crude annual incidence for invasive cutaneous malignant melanoma was 77.7/100,000. The age-standardized annual rate was 56.2/100,000 with no statistically significant differences in the rates for males and females. The cumulative risk of developing melanoma over a lifetime, from age 0 to 74, was 5.7% overall. The age-specific rates steadily increase with advancing age. The lesions were generally thin; 64% were less than 0.76 mm, and only 7% were thicker than 3.00 mm. In conclusion, the Caucasian population in the Auckland region has the highest incidence of melanoma in the world.

Abstract.: The calculation of incidence rates of melanoma in New Zealand has been hampered in the past by incomplete registration of cases. The aim of this study was to document the incidence of melanoma in the Auckland Caucasian population and to define the pathologic characteristics of these lesions. Data were collected for the Auckland region from the New Zealand Cancer Registry and the Auckland Melanoma Unit database for 1995 and combined with census statistics to give the crude and age-standardized rates for invasive melanoma. The results were analyzed by gender, morphology, body site, and thickness. The crude annual incidence for invasive cutaneous malignant melanoma was 77.7/100,000. The age-standardized annual rate was 56.2/100,000 with no statistically significant differences in the rates for males and females. The cumulative risk of developing melanoma over a lifetime, from age 0 to 74, was 5.7% overall. The age-specific rates steadily increase with advancing age. The lesions were generally thin; 64% were less than 0.76 mm, and only 7% were thicker than 3.00 mm. In conclusion, the Caucasian population in the Auckland region has the highest incidence of melanoma in the world.

The purpose of this study was to identify risk factors for fetal loss and other pregnancy complications associated with genetic amniocentesis. Data were acquired in the Canadian Early Amniocentesis Trial (CEMAT), a multicentred (12) prospective, randomized trial comparing continuous ultrasound-guided early amniocentesis (EA) and mid-trimester amniocentesis (MA) (CEMAT Group, 1998). Details of the procedure were recorded and analysed by allocation (EA versus MA), operator and centre, and correlated with pregnancy outcome. A total of 62 spontaneous pregnancy losses occurred between the procedure and 20 weeks' gestation among the 3691 patients who received their procedures within the allocated window (EA=53/1916, MA=9/1775). Technical factors correlating with these losses included procedures ‘judged to be difficult’ by the operator, and post-procedure amniotic fluid leakage or bleeding. Maternal risk factors included maternal hypertension (fetal loss 11.1 per cent, compared with non-hypertensive women, 2.6 per cent) increased body mass index (BMI) and gravidity of three or greater. Allocation to EA was predictive of fetal loss, as well as failed procedure, multiple needle insertions, amniotic fluid leakage, failed culture and talipes equinovarus, in excess compared with MA. In conclusion, in this large prospective randomized trial evaluating amniocentesis, specific maternal, fetal and procedural variables were found to be predictive of fetal loss and adverse pregnancy outcome. Performing amniocentesis before 13 weeks' gestation (EA) was the major predictive factor for adverse outcome. These data suggest that first-trimester chorionic villus sampling (CVS) and MA will likely remain the invasive procedures of choice for evaluation of fetal karyotype. Copyright © 1999 John Wiley & Sons, Ltd.

Biophysical profile scoring was the principal technique of antepartum fetal surveillance in 238 well-controlled diabetic pregnancies. Fifty insulin-dependent diabetics had twice-weekly testing, and 188 gestational diabetics had weekly testing. Intervention was not pursued unless there were maternal or fetal complications. There were no stillbirths and three neonatal deaths, all resulting from congenital anomalies, giving a corrected perinatal mortality rate of 0. The incidence of abnormal biophysical profile scores, eight of 238 (3.3) overall, was low, with no significant difference between types of diabetics. In those with an abnormal score, intervention was mandated; the cesarean section rate was 50 and the rate of intensive care nursery admissions was high. Of the 230 fetuses with a normal biophysical profile score, 200 (87) were delivered at term with minimal maternal or neonatal morbidity. Amniocentesis for phospholipid profile was performed in only 33 cases (13.9). Hyaline membrane disease was confined to five premature neonates (incidence 2.1). We conclude that antepartum fetal surveillance using the biophysical profile score permits safe expectant management in the diabetic pregnancy, yielding significant clinical advantages to both mother and fetus.

A pneumatic tube system suitable for transportation purposes is simulated in an experimental facility. The vehicle position, velocity and corresponding system pressures were obtained and are presented for representative test runs. An analysis for prediction of these quantities during the transit of a vehicle through a tube under conditions of fixed inlet pressure and discharge volume flow rate is also presented. This analysis is applied to the experimental operating conditions and is shown to predict the experimental results closely and to be applicable to the prediction of the performance of prototype pneumatic tube systems over a significant range of interest.

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.

A method for increasing the peak output of steam power plants through use of a low-pressure feedwater storage system is presented. The generalized availability analysis involves only the low-pressure turbine, low-pressure feedwater heaters, and the storage system. With daily cycling and storage charging at near base load conditions, the turnaround efficiency of the energy storage system was found to approach 100 percent. Storage system turnaround efficiency is decreased when the energy is stored during plant part-load operation.

Standard central difference operators are typically very poor at approximating derivatives in the vicinity of singularities. In such cases geometric sequences have been used successfully as the basis for defining difference operators up to second order which give excellent approximation. In this paper, geometric difference methods are used to find operators of all orders n which give exact higher derivatives for functions of the form αx-1 + ∑nm=0 βmxm. Surprisingly good analogies are found with classical results and some numerical and computational comparisons are made

For two dimensional problems with radial symmetry, the standard numerical scheme applied to Laplace's equation uses the polar form of the equation together with a radial grid based upon equal increments of angle and equal increments of radius. However the resulting numerical scheme contains a fundamental difficulty - it includes an r-1 component which can lead to computational inaccuracy near the origin. In this paper a numerical scheme is devised with radial points arranged in non-uniform geometric sequence. The resulting finite difference scheme for Laplace's equation is remarkably concise, is well-behaved at the origin, and the corresponding grid is a natural radial analogue of the standard rectangular grid. Analytical comparisons are made with the standard scheme and computational experiments on an example from electromagnetics indicate significant improvement in accuracy.

An externally pressurized compliant air bearing with potential for operation on surfaces of moderate unevenness or roughness such as might be encountered in vehicle guideways is considered. Analytical results are presented which show the effect on load carrying capacity, flow requirement, and center of pressure location of variation of bearing compliance, surface roughness, bearing speed, and bearing slope.

Composite biophysical profile scoring as a method of determining fetal health is discussed. The major premise is that, with appropriate testing, nearly all fetuses with chronic asphyxia in utero, the majority of patients with congenital anomalies, and a lesser proportion of fetuses at risk for acute asphyxia can be detected in utero.

Grids based on geometric and harmonic sequences are used here in defining approximations to derivatives which have second order accuracy. Such schemes are superior to the usual arithmetic difference grids for important classes of functions exhibiting significant variation - such as a singularity in a region. Furthermore, the approximations to derivatives are exact in certain cases. First and second difference operators based on the geometric mean give exact results for functions of the form ax + b + cx-1, and operators based on the harmonic mean give exact results for functions of the form a+bx-1+cx-2 This unifies the well-known result for arithmetic differences, which give exact derivatives for second degree polynomials, and demonstrates yet another surprising connection between arithmetic, geometric and harmonic means.

We investigate how the effectiveness of green infrastructure (GI) to mitigate the frequency and magnitude of significant discharge events and combined sewer overflows (CSOs) depend on both climate and sewershed characteristics and propose a theoretical framework for a holistic assessment of GI's efficacy. The framework is based on the comparison of three characteristic timescales that control the production of peak discharge: rainfall duration (tr), travel time in the sewer network (tn), and the duration of rain that would be required to fill the GI's storage (tGI). Storm events can then be characterized by two ratios of these timescales: Tn= tn/tGIand Tr= tr/tGI.A third dimensionless number characterizes critical storms during which adverse events (such as CSOs) occur and allows us to identify the combinations of Tnand Trfor which GI may substantially mitigate those events. The results of numerical experiments with the model demonstrate that the storms for which GI can substantially reduce peak discharge and CSO volume typically occur in a narrow band of Tnand Tr. Within that band, the efficacy of GI may depend on the location of GI within the sewershed if network routing substantially affects the timing and magnitude of flood peaks. The proposed framework is applied to examine the efficacy of GI using historical precipitation data from two major U.S. cities: Philadelphia, PA, and Seattle, WA, and the results of this comparative analysis suggest that GI location is an important control on catchment‐scale GI efficacy in Philadelphia, but less so in Seattle. Combined sewer overflows (CSO) occur when storm rainfall exceeds the capacity of the sewer system to drain it. Green infrastructure (GI) is intended to mitigate the occurrence and severity of CSOs. But how effective will it be in helping to manage CSOs? Here we present a theoretical framework to address this question, by focusing on the major physical controls on the efficacy of GI for managing CSOs, including the relative roles of climate, the size of the sewershed, and the location of the GI within it. The framework is based on three characteristic timescales: storm duration, travel time to the overflow location, and time required to fill GI storage. We use the framework to explore how GI might work differently in different places. The results show that GI is most effective under certain combinations of climate and sewershed conditions, and that the location of GI within the sewershed can be very critical. The latter effect was found to be more evident, for example, in Philadelphia, PA, than in Seattle, WA, due to differences in storm duration and intensity between these two places. In these ways, the proposed framework can support green infrastructure planning by providing insights on location‐effectiveness tradeoffs. The ability of GI to mitigate peak discharge depends on the climate and sewershed characteristics, as well as its designWe propose a simple framework for capturing these controls in terms of timescales and three dimensionless numbersGI efficacy in treating CSO volume and frequency may depend on the precipitation pattern and the location of GI within a sewershed

Many catchment studies use estimates of stream age distributions, including transit time distributions and StorAge Selection (SAS) functions, to make inferences about hydrologic processes and dominant flow paths. To improve the basis for such inferences, this study examined how different hydrologic flow paths contribute to the age distribution of discharge and evapotranspiration (ET) at the U.S. Department of Agriculture's Mahantango Creek experimental catchment in PA, USA, using the integrated surface‐subsurface hydrology model Parallel Flow‐Common Land Model with SLIM‐FAST particle tracking. The model tracked ET and five flow paths: direct runoff, overland flow, interflow, and shallow and deep groundwater. Over a 1‐year simulation, we found that individual flow paths release generally olderage‐rank storage under wetting conditions (a direct storage effect). Paradoxically, total discharge originated from youngerage‐rank storage under wetting conditions (an inverse storage effect). This inverse storage effect was caused by the disproportionate increase in contributions from younger flow paths, particularly overland flow. This result suggests that where direct storage effects have been observed for individual sources of discharge (such as shallow groundwater), the same may not necessarily hold for total discharge and could in fact be reversed. Other findings include (1) a highly nonunique mapping between water age and flow path, (2) a “middle‐aged depression” in stream ages that cannot be fit by unimodal distributions (e.g., gamma and beta), (3) a taxonomy of transit time distribution shapes that occur during a typical storm, and (4) relatively young ET age distributions with a time‐invariant SAS function shape that reflects the parameterized depth distribution of root‐water uptake. How does rainfall and the pollution it carries get into streams? How much travels overland, through soils, or deep underground? Hydrologists have used a variety of methods to understand the flow pathways of water, including studies of the age of the water, which is defined as the amount of time that has passed since water in the environment fell as rain. In this study, we use site measurements and a detailed computer model in a well‐studied farmland to simulate the movement and ages of water along five different flow paths that feed into a stream. To make our results more relevant to other research, we describe water ages in the stream relative to water ages in the ground. As has been found in other locations, we find that stream water tends to become younger after heavy rain. One might therefore expect that flow paths feeding the stream would also become younger after heavy rain. In fact, they generally become older. This apparent contradiction is explained by the fact that one of the youngest flow paths, overland flow, not only gets older under wet conditions but also gets larger and drives down the average age of the entire stream. Integrated watershed model tracked flux and age of seven hydrologic flow paths contributing to Qand ETFlow paths have overlapping ages, which confounds mechanistic interpretation of transit timesInverse storage effect caused by shifting proportion—not shifting age—of each flow path

Clavulanic acid, a beta-lactamase inhibitor, was found to be associated with the development of a positive direct antiglobulin test. Of 23 antibiotic courses in patients treated with ticarcillin, clavulanic acid, and tobramycin, 10 (43.5%) developed positive direct antiglobulin tests versus 2 of 26 (7.7%) patients treated with piperacillin and tobramycin (P = 0.0044). In vitro immunohematological studies showed that clavulanic acid caused a nonimmunologic adsorption of plasma proteins onto the erythrocyte surface. Hemolysis was not associated with such nonimmunologic adsorption. However, the resulting positive antiglobulin test might delay cross matching of blood products for transfusions or interfere with the evaluation of true immune-mediated hemolytic anemia.

EXPERIMENTAL models of gallstone formation have been described in many species1,2, but the lithogenic methods used were unphysiological or unnatural. In dogs, spontaneous gallstones are rare1, and human cholesterol gallstones placed in the dog gallbladder will dissolve3. Canine gallstones occur in biliary fistulas4, but the only report of gallbladder stones followed combined cholesterol-feeding and occlusion of the cystic duct5. To induce stones physiologically in this resistant species, we designed a diet in 1965 which hypothetically would alter bile salt–phospholipid–cholesterol–pigment relationships in bile and cause bile stasis as follows: low amounts of protein, high content of sugar and no added bile salts to reduce total bile salt and volume-flow of bile6,7; low content of total and unsaturated fat to reduce and alter phospho-lipids and bile salts in bile and to decrease gallbladder contractions8–10; and added cholesterol to overcome the cholesterol-holding capacity of dog bile1,11. Cornstarch and multiple small feedings were added further to simulate diets of certain human populations with a high incidence of cholelithiasis, for example, the Pima Indians12, or produce biliary stasis1,8. The diet was compounded of purified casein 10 per cent, sucrose 50 per cent, cornstarch 26 per cent, animal lard 5 per cent, cholesterol USP 1 per cent, salt mixture USP XIV 5 per cent, ‘Vitamin Diet Fortification Mixture’ 2 per cent and cellulose as filler 1 per cent (Nutritional Biochemicals Corporation, Cleveland, Ohio).

Nebulized pentamidine is increasingly used for the prevention of Pneumocystis carinii pneumonia in HIV antibody-positive patients. We report our experience of the efficacy and tolerance of a high dose regimen (300 mg every second week) in 173 HIV-positive patients over a 2½-year period. Only seven episodes of P. carinii pneumonia occurred but 48 patients (28 per cent) died of other AIDS-related illnesses. Patients who had never had an episode of P. carinii infection were less likely to accept long-term prophylaxis (17 of 81), compared to those who had previously been treated for the condition (five of 92). Nebulized pentamidine is an effective form of prophylaxis against P. carinii pneumonia, but long-term mortality is still high in AIDS patients. Side-effects with this regimen were almost always local and confined to the period of nebulization.