Global forecasts in reservoir computers.

A reservoir computer is a machine learning model that can be used to predict the future state(s) of time-dependent processes, e.g., dynamical systems. In practice, data in the form of an input-signal are fed into the reservoir. The trained reservoir is then used to predict the future state of this signal. We develop a new method for not only predicting the future dynamics of the input-signal but also the future dynamics starting at an arbitrary initial condition of a system. The systems we consider are the Lorenz, Rossler, and Thomas systems restricted to their attractors. This method, which creates a global forecast, still uses only a single input-signal to train the reservoir but breaks the signal into many smaller windowed signals. We examine how well this windowed method is able to forecast the dynamics of a system starting at an arbitrary point on a system's attractor and compare this to the standard method without windows. We find that the standard method has almost no ability to forecast anything but the original input-signal while the windowed method can capture the dynamics starting at most points on an attractor with significant accuracy.

Environmental and travel factors related to leptospirosis in Thailand.

To identify potential environmental and travel factors related to leptospirosis, we conducted an unmatched case controlled study and household assessment of cases and controls in Nakhon Ratchasima province (north-eastern, Thailand) from August to December, 1998. Fifty-six cases and 145 controls were included in the study. Cases were hospitalized patients who had been diagnosed with leptospirosis and tested positive for anti-leptospiral IgM antibody using the Panbio ELISA (Panbio Inc, Brisbane, Australia). Controls were the neighbors of cases who had tested negative. Standardized questionnaires and household assessments were used to collect information on demographics, number of animals kept, evidence of rats in the home, presence of rat food inside the home, road characteristics, awareness of leptospirosis disease, environment, and travel history. Multivariant, unconditional logistic regression demonstrated that travel on potholed roads was independently associated with leptospirosis infection (OR 5.0; 95%CI 1.2-20.2) and traveling by car was a protective factor (OR 0.2; 95%CI 0.06-0.9).

Blastocyst-ET and monozygotic twinning.

PURPOSE: To examine the rate of monozygotic twinning associated with blastocyst transfer using commercially available, cell-free culture systems with unmanipulated blastocysts. METHODS: A retrospective analysis was conducted in multiple private and academic infertility centers throughout the United States, of 199 pregnant patients following in vitro fertilization (IVF) blastocyst embryo transfer (ET). Human embryos obtained through standard IVF stimulation protocols were cultured in commercially available, cell-free media systems and transferred as blastocysts. The main outcome measure was the rate of monozygotic twinning. RESULTS: A total of 199 blastocyst-ET pregnancies were achieved during the study period at the fertility centers examined. Monozygotic twinning was noted in 10/199 (5%) of these pregnancies. All were monochorionic diamnionic. CONCLUSIONS: Monozygotic twinning previously has been reported following IVF, especially in relation to assisted hatching. While blastocyst transfer has been available for many years using coculture, there have been no published multicenter reports of monozygotic twinning associated with unmanipulated blastocysts. In a multicenter analysis, a definite increase in monozygotic twinning was seen following blastocyst-ET. We believe this phenomenon is real and that this information should be considered when counseling patients for treatment.

Effects of visible and invisible cueing procedures on perceptual judgments in young and elderly subjects.

Healthy subjects were tested in two experiments to examine the effects of lateralized cues on line bisection and landmark judgments. The studies were designed to investigate whether bisection and landmark biases induced by cueing are simply a result of a direct perceptual lengthening of the cued part of the line caused by the fact that the cue is visible, thus creating a composite 'line plus cue' or whether cueing induces an attentional bias operating on judgments of spatial extent by either reducing the magnitude of the parts of the stimulus receiving 'less' attention or magnifying those parts receiving 'more'. Lateralized cues were either visible letter cues or invisible marks drawn with a leadless pencil either by the subject him/herself (Experiment 1) or the experimenter (Experiment 2). Comparable to a previous study (Mattingley, Pierson, Bradshaw, Phillips and Bradshaw, 1993, Neuropsychologia, 31, 1201-1215), the first experiment showed that only visible cues affected line bisection and landmark judgments thus favouring the perceptual explanation. The second study, however, revealed bisection and judgment biases for invisible as well as visible cues with the attended part of the line appearing subjectively longer. These results indicate that attentional modulations can increase the salience of a line in a similar vein to physical changes. It seems likely that the requirement of a motor response in Experiment 1 cancelled out all attentional properties supposedly induced by placing that invisible cue.

Embryo nutrition and energy metabolism and its relationship to embryo growth, differentiation, and viability.

Over the past decade there has been a resurgence of interest in the culture media used in clinical in vitro fertilization. Unfortunately, during this time more confusion than consensus appears to have developed regarding the composition of these media. In order to facilitate a clearer understanding of this field, it is important to understand the role of specific medium components and how their use is regulated by the embryo. The roles of the key nutrients glucose, pyruvate, lactate, and amino acids during the preimplantation period have therefore been presented. Analysis of how the embryo regulates the utilization of such nutrients has led to a clearer understanding of the embryo's requirements during the dynamic period of preimplantation development. From such information, sequential culture media have been developed along with novel noninvasive tests of embryonic viability. It is proposed that continued studies on the human embryo will lead to further improvements in embryo culture conditions and the optimization of viability assays, culminating in the ability to transfer single embryos for the majority of, if not all patients.

Preliminary clinical experience with human blastocyst development in vitro without co-culture.

This preliminary analysis was designed to quantify blastocyst development of supernumerary embryos without the use of feeder cells, conditioned medium or whole serum. Embryos derived from in-vitro fertilization (IVF) that were not transferred or cryopreserved were included in this study. Ova were harvested for IVF after a standard ovarian stimulation with gonadotrophin-releasing hormone agonist/ human menopausal gonadotrophin (GnRHa/HMG) or follicle-stimulating hormone (FSH). Ova were collected and culture in 150 microliters droplets of P1 medium under mineral oil, in groups at 37 degrees C under 5% CO2, 5% O2, 90% N2 (group A) or under 5% CO2 in air (group B) environment. Embryo transfer was performed 72 h post-harvest. Viable embryos not transferred or cryopreserved were placed in blastocyst medium and cultured for an additional 48 h in 5% CO2 in air. Embryos that exhibited an expanded blastocoelic cavity and well-defined inner cell mass at 120 h were counted. Of 838 supernumerary embryos cultured, 448 (53.5%) reached the expanded blastocyst stage by 120 h of culture. Patients were given the option of cryopreservation at that time. The embryos were cryopreserved using a standard protocol with serial addition of glycerol. Embryos reaching the blastocyst stage after more than 120 h of culture were not included. There was no difference in the proportions of blastocyst development between group A, 217/410 (53.5%) and group B, 231/428 (54%). To date, 16 patients have each had up to three thawed blastocysts transferred, out of whom seven became pregnant. This report demonstrates that a simple system of sequential culture generated acceptable, viable blastocyst development (54%) with supernumerary embryos, without the use of feeder cells, conditioned medium or whole serum. Recognizing the differential metabolic requirements of early and late cleavage stage embryos has enabled the application of a glucose/phosphate-free simple culture medium (P1) for up to 72 h of culture and a complex, glucose-containing medium (blastocyst medium) for subsequent blastocyst development.

Epigastric pain and sonographic assessment of the pancreas in dengue hemorrhagic fever.

PURPOSE: This study reports the sonographic features of the pancreas in children who have dengue hemorrhagic fever (DHF) with epigastric pain, evaluates pancreatic abnormalities as the source of this pain, and relates sonographic findings, DHF status, and serum levels of amylase and lipase. METHODS: Over 3.5 years, real-time sonographic examination of the pancreas was prospectively performed in 148 children (age range, 5 months-14 years) who had DHF with epigastric pain. The DHF diagnosis was confirmed by serologic examination and viral isolation. RESULTS: Of the 142 children included in this study, 72 had mild DHF (grade I or II) and 70 had severe DHF (grade III or IV). An enlarged pancreas was found in 41 patients (29%), 10 (14%) of whom had mild DHF and 31 (44%) of whom had severe DHF. The pancreas was hyperechoic relative to the liver in 36 patients (25%), isoechoic in 98 (69%), and hypoechoic in 8 (6%). CONCLUSIONS: The majority of patients with DHF and epigastric pain do not have an enlarged pancreas, different echogenicity of the pancreas compared with the liver, or a dilated pancreatic duct. Thus, pathologic changes of the pancreas cannot be the only cause of epigastric pain in DHF patients. Increased serum levels of amylase and lipase are commonly seen in patients with severe DHF and an enlarged pancreas.

Improved clinical outcomes for in vitro fertilization with delay of embryo transfer from 48 to 72 hours after oocyte retrieval: use of glucose- and phosphate-free media.

OBJECTIVE: To evaluate clinical outcomes of day 2 versus day 3 ET using a culture media with no glucose or phosphate. DESIGN: Retrospective clinical study. SETTING: Hospital-based fertility clinic. PATIENT(S): One hundred seventy-six IVF-ET patients undergoing controlled ovarian supraovulation. INTERVENTION(S): IVF and delaying the ET by 1 day. MAIN OUTCOME MEASURE(S): Number of blastomeres per embryo, implantation and pregnancy rates. RESULT(S): Delaying the ET from day 2 to day 3 after oocyte retrieval significantly increased implantation rates (13% versus 24%) and ongoing/delivered pregnancy rates per retrieval (26% versus 44%). Day 3 embryos with > or = 8 blastomeres resulted in a significantly higher pregnancy rate (53%) than day 3 embryos with < 8 cells (23%) and day 2 embryos with > or = 4 cells (31%) or < 4 cells (11%). CONCLUSION(S): Day 3 ET was associated with a significant increase in implantation and pregnancy rates. Delaying the ET until day 3 may permit the selection of more viable embryos than on day 2. The absence of glucose and phosphate from the culture media is compatible with good IVF outcomes.

Dengue haemorrhagic fever: ultrasound as an aid to predict the severity of the disease.

In a prospective study, the relationship between the clinical severity of dengue haemorrhagic fever (DHF) and the sonographic findings was examined. The study comprised 73 cases classified as mild (grades I-II) and 75 as severe (grades III-IV). Ultrasonography in the mild group revealed pleural effusions in 30%, ascites in 34%, gallbladder wall thickening in 32%, hepatomegaly in 49%, splenomegaly in 16%, and pancreatic enlargement in 14%. In the severe group, pleural effusions, ascites and gallbladder wall thickening were found in 95%, pararenal and perirenal fluid collections in 77%, hepatic and splenic subcapsular fluid collections in 9%, pericardial effusion in 8%, hepatomegaly in 56%, splenomegaly in 16%, and pancreatic gland enlargement in 44%. Ultrasound may be useful for early prediction of the severity of DHF in children.

Gallbladder wall thickening in dengue hemorrhagic fever: an ultrasonographic study.

This study attempts to investigate whether gallbladder wall thickening (GBWT) measured by ultrasonography can be used in children as a reliable criterion to predict the onset of severe dengue hemorrhage fever (DHF). In this prospective study, we performed ultrasound examinations focusing on the gallbladder wall and the presence of intraperitoneal free fluid in 48 mild DHF cases (grades I-II) and 48 severe cases (grades III-IV). GBWT varied between 1 mm and 8 mm with a mean of 3.77 mm +/- 2.04 mm. The mean value of DHF grades I and II (2.39 mm +/- 1.48 mm) is significantly lower than that of grades III and IV (5.14 mm +/- 1.54 mm), p < 0.001. GBWT exceeded 3 mm in only 16 of 48 (33.3%) grade I-II patients and in 45 of 48 (93.8%) grade III-IV patients. A significant positive correlation was apparent between GBWT and the severity of illness, p < 0.001. Patients with ascites have significantly thicker gallbladder walls than those without, p < 0.01. In clinically confirmed DHF cases, the sonographic finding of GBWT > 3 mm to 5 mm, with 93.8% sensitivity, can be used as a criterion indicating the need for admission and monitoring. A GBWT of > or = 5 mm, with 91.7% specificity, is useful as a criterion for identifying DHF patients at high risk of developing hypovolemic shock.

Synthetic serum substitute (SSS): a globulin-enriched protein supplement for human embryo culture.

OBJECTIVE: The purpose of the present study was to evaluate whether an IVF protein supplement prepared from human serum albumin (HSA) and human globulins would retain performance characteristics equivalent to those reported for the commercial plasma expanders, Plasmatein (Alpha Therapeutics, Los Angeles, California) and Plasmanate (Cutter Biological, Miles Inc., Elkhart, Indiana). METHODS: Pronuclear-stage human embryos were randomly divided and cultured in human tubal fluid medium (HTF) supplemented with either HSA (5 mg/mL) or Plasmatein (10%, v/v; 5 mg/ml) as a means of indirectly assessing the effect alpha- and beta-globulins have on embryonic development. Those results coupled with the known composition characteristics of Plasmatein were used as the starting basis to formulate test lots of synthetic serum substitute (SSS). RESULTS: Significantly (P < 0.05) more of the human embryos cultured in Plasmatein supplemented medium reached the four-cell or greater stage by 40 hr postinsemination than a comparable group cultured in HSA alone. Lot 1 of SSS, formulated with HSA (84% of total protein) and human globulins (16% of total protein) and an aqueous lipoprotein fraction derived from human plasma (Excyte IV; Miles Diagnostics, Kankakee, Illinois), produced accelerated early embryonic growth relative to control murine embryos grown in the presence of Plasmatein, however, the percentage of the embryos reaching the hatched blastocyst stage was decreased (45 vs 100%). Human embryos from seven patients, randomized to HTF medium supplemented with Plasmatein or lot 1 of SSS, showed equivalent growth at 36-40 hr postinsemination. A microprecipitate developed in media supplemented with lot 1 after several days of culture. The Excyte IV concentration was reduced and, ultimately, eliminated from the subsequent and final prototype lots of SSS. Murine embryos grown in the presence of lipoprotein free SSS showed significantly accelerated (P < 0.01) growth at 17 hr postthaw compared to Plasmatein and all embryos progressed to hatching by 41 hr. Human embryos, randomized to either Plasmatein or lot 3 of SSS, showed significantly accelerated growth (P < 0.01) when scored at 38 hr following insemination. CONCLUSION: Synthetic serum substitute provides a convient, standardized means of adding protein to media used in assisted reproductive technology (ART) procedures.

A simple approach to intracytoplasmic sperm injection.

OBJECTIVE: To describe a simple injection apparatus and method for performing intracytoplasmic sperm injection in a clinical IVF program. DESIGN: A prospective clinical trial of intracytoplasmic sperm injection. SETTING: A private office-based fertility program. PATIENTS: Five couples undergoing IVF-ET with intracytoplasmic sperm injection as a treatment for male factor infertility. INTERVENTIONS: Intracytoplasmic sperm injection was performed at room temperature (23.5 to 24.5 degrees C) in a simple zwitterion-buffered medium. MAIN OUTCOME MEASURES: Fertilization rates, cleavage rates, clinical pregnancy rates, implantation rates. RESULTS: Intracytoplasmic sperm injection was performed on 44 fresh oocytes from five patients. Twenty-three oocytes fertilized (52.3%) and 22 zygotes cleaved (95.7%). Three of five patients became pregnant (60%), resulting in the live birth of one normal male infant, one continuing singleton pregnancy, and one continuing twin gestation (46XX, 46XY). The implantation rate was 23.5%. CONCLUSION: Intracytoplasmic sperm injection can be performed successfully in a simple medium at room temperature using commercially available microtools.

Optical analyses of eyeglass lens fragments and the unexpected detection of oral sperm in a homicide case.

A homicide case in which intact spermatozoa were found in the oral cavity of the deceased forty days after his disappearance is reported. The victim's partially frozen body was found outdoors in a wooded area of upstate New York during the month of January. During a subsequent investigation, pieces of eyeglass lens fragments and bloodstains were found in the suspect's house and vehicle. Chemical and optical analyses of the lens fragments are presented as well as results of the serological tests.

High continuing pregnancy rates after in vitro fertilization-embryo transfer using medium supplemented with a plasma protein fraction containing alpha- and beta-globulins.

OBJECTIVE: To evaluate both the laboratory and clinical outcomes after IVF-ET using culture media supplemented with a plasma protein fraction (PPF, Plasmatein; Alpha Therapeutics, Los Angeles, CA) containing albumin and significant amounts of alpha- and beta-globulins. DESIGN: One-year clinical trial of a PPF with high globulin content as a medium supplement during IVF, embryo growth, and ET. SETTING: Fertility Center of San Antonio, a private, office-based center for assisted reproduction. PATIENTS: Ninety-eight couples, with women ranging in age from 26 to 46 years, undergoing 103 ovum retrievals for IVF-ET as treatment for infertility because of tubal factor, endometriosis, anovulation, uterine or cervical factor, male factor, and unexplained causes. MAIN OUTCOME MEASURES: Fertilization rate, zygote cleavage rate, clinical pregnancy rate (PR), continuing PRs, and implantation rates. RESULTS: Supplementation with PPF in insemination, growth and transfer medium resulted in a clinical PR of 41.5% per transfer with continuing PRs of 35.2% per retrieval, 37.2% per patient, and 38.7% per transfer. CONCLUSIONS: A PPF containing significant amounts of alpha- and beta-globulins can serve as an effective protein supplement to IVF medium, with outcomes manifested as high continuing PRs. These data indicate a potential role for glycoprotein components of serum in supporting healthy embryo growth in vitro, although the mechanism may relate more to the general physicochemical properties of this fraction than to the actions of a specific component.

Coordinated delivery of clinical care: the "re-integration" of the medical group practice.

This paper suggests that for medical knowledge to be effective, it must be reliably translated into a series of synchronized activities, both clinical and operational. The goal of medical information science must be not only to identify the best course of care, but also through the use of systems for the ordering, scheduling, and deployment of staff and resources to assure that the planned course of care is reliably and efficiently delivered in actual practice settings. We present a brief history of several innovations in patient care coordination and logistics at Mayo Clinic to provide background for the main concepts presented. The principle of patient care coordination underlying this history of innovation is shown to have evolved into a new need for information systems capable of proactively effecting the delivery of care through patient, staff and resource deployment and monitoring.