Comparative sequencing in the genus Lycopersicon. Implications for the evolution of fruit size in the domestication of cultivated tomatoes.

Sequence variation was sampled in cultivated and related wild forms of tomato at fw2.2--a fruit weight QTL key to the evolution of domesticated tomatoes. Variation at fw2.2 was contrasted with variation at four other loci not involved in fruit weight determination. Several conclusions could be reached: (1) Fruit weight variation attributable to fw2.2 is not caused by variation in the FW2.2 protein sequence; more likely, it is due to transcriptional variation associated with one or more of eight nucleotide changes unique to the promoter of large-fruit alleles; (2) fw2.2 and loci not involved in fruit weight have not evolved at distinguishably different rates in cultivated and wild tomatoes, despite the fact that fw2.2 was likely a target of selection during domestication; (3) molecular-clock-based estimates suggest that the large-fruit allele of fw2.2, now fixed in most cultivated tomatoes, arose in tomato germplasm long before domestication; (4) extant accessions of L. esculentum var. cerasiforme, the subspecies thought to be the most likely wild ancestor of domesticated tomatoes, appear to be an admixture of wild and cultivated tomatoes rather than a transitional step from wild to domesticated tomatoes; and (5) despite the fact that cerasiforme accessions are polymorphic for large- and small-fruit alleles at fw2.2, no significant association was detected between fruit size and fw2.2 genotypes in the subspecies--as tested by association genetic studies in the relatively small sample studied--suggesting the role of other fruit weight QTL in fruit weight variation in cerasiforme.

Reducing the cost of frequent hospital admissions for congestive heart failure: a randomized trial of a home telecare intervention.

BACKGROUND: The high cost of caring for patients with congestive heart failure (CHF) results primarily from frequent hospital readmissions for exacerbations. Home nurse visits after discharge can reduce readmissions, but the intervention costs are high. OBJECTIVES: To compare the effectiveness of three hospital discharge care models for reducing CHF-related readmission charges: 1) home telecare delivered via a 2-way video-conference device with an integrated electronic stethoscope; 2) nurse telephone calls; and 3) usual outpatient care. RESEARCH DESIGN: One-year randomized trial. SUBJECTS: English-speaking patients 40 years of age and older with a primary hospital admission diagnosis of CHF. MEASURES: Our primary outcome was CHF-related readmission charges during a 6-month period after randomization. Secondary outcomes included all-cause readmissions, emergency department (ED) visits, and associated charges. RESULTS: Thirty-seven subjects were randomized: 13 to home telecare, 12 each telephone care and 12 to usual care. Mean CHF-related readmission charges were 86% lower in the telecare group ($5850, SD $21,094) and 84% lower in the telephone group ($7320, SD $24,440) than in the usual care group ($44,479, SD $121,214). However, the between-group difference was not statistically significant. Both intervention groups had significantly fewer CHF-related ED visits (P = 0.0342) and charges (P = 0.0487) than the usual care group. Trends favoring both interventions were noted for all other utilization outcomes. CONCLUSIONS: Substantial reductions in hospital readmissions, emergency visits, and cost of care for patients with CHF might be achieved by widespread deployment of distance technologies to provide posthospitalization monitoring. Home telecare may not offer incremental benefit beyond telephone follow-up and is more expensive.

fw2.2 directly affects the size of developing tomato fruit, with secondary effects on fruit number and photosynthate distribution.

fw2.2 is a quantitative trait locus responsible for approximately 30% of the difference in fruit size between large, domesticated tomatoes (Lycopersicon esculentum Mill.) and their small-fruited wild relatives. The gene underlying this quantitative trait locus was cloned recently and shown to be associated with altered cell division in ovaries (Frary et al., 2000). However, it was not known whether the change in fruit size is associated with other changes in plant morphology or overall fruit yield-changes that could potentially cause the fruit weight phenotype. To shed light on this issue, a detailed comparison was made between nearly isogenic lines differing for alleles at this locus to search for pleiotropic effects associated with fw2.2. Field observations show that although the small-fruited nearly isogenic line produced smaller ovaries and fruit as expected, this was compensated by a larger number of fruit-due mainly to a significantly greater number of inflorescences-but with no net change in total fruit mass yield. This strongly suggests that fw2.2 may have a pleiotropic effect on how the plant distributes photosynthate among fruit. In a flower removal experiment to control for differences in inflorescence size and number, fruit size remained significantly different between the nearly isogenic lines. These observations indicate that the primary effect of fw2.2 is in controlling ovary and fruit size, and that other associated phenotypic effects are secondary.

Development of a telemedicine program: a review of 1,000 videoconferencing consultations.

OBJECTIVE: To examine the financial and organizational characteristics, demand for services, and satisfaction outcomes of a growing telemedicine program serving both urban or suburban and rural populations. DESIGN: Retrospective review of 1,000 consecutive telemedicine consultations in the University of California (UC) Davis Telemedicine Program. SETTING: Telemedicine videoconferencing units, used to integrate care in the UC Davis Health System among the UC Davis Medical Center and several urban or suburban primary care clinics, rural hospitals, and clinic affiliates. SUBJECTS: A total of 657 consecutive patients who consented to a telemedicine consultation. Main outcome measures Demographic information about the patient population, the rural and urban or suburban clinics, the types of specialty consultations, and telemedicine equipment used in the UC Davis Health System. Patient and physician satisfaction were measured on a 5-point Likert scale. RESULTS: Patients and primary care physicians reported high levels of satisfaction. Rural clinics requested more and a greater variety of specialist consultations than urban or suburban clinics. CONCLUSION: Although referring physicians and patients indicate a high level of satisfaction with telemedicine services and insurers are negotiating reimbursement policies, additional research must investigate the reasons why some payers, patients, and providers resist participation in these services.

Hybrid system for telepathology.

We introduce a novel hybrid telepathology system providing simultaneous transmission of both real-time microscopy and static imagery at a reasonable cost. It is capable of capturing static, true color images at resolution of 1,520 x 1,144 pixels and providing live transmission of real-time video images of the glass slide in Common Intermediate Format (CIF), which can be viewed at 1,024 x 768 pixels or higher. Instant freeze function can be enabled with 4x CIF resolution (1,408 x 1,152 pixels). This system comprises the advantages of real-time transmission and high-resolution static imagery, while direct visual and audio communications are maintained at the same time. It uses standard 'off-the-shelf' components with a total cost of around $30,000 to $40,000. We also conclude that differences in telepathology modality and image quality have an impact on diagnostic accuracy and should be considered for discussion and standards development by professional organizations in the field of telepathology. An effort to ascertain the diagnostic limitations of various telepathology modalities is essential to the future use of this modality of pathology practice.

fw2.2: a quantitative trait locus key to the evolution of tomato fruit size.

Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL), fw2.2, was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the fw2.2 region of a small-fruited wild species reduced fruit size by the predicted amount and had the gene action expected for fw2.2. The cause of the QTL effect is a single gene, ORFX, that is expressed early in floral development, controls carpel cell number, and has a sequence suggesting structural similarity to the human oncogene c-H-ras p21. Alterations in fruit size, imparted by fw2.2 alleles, are most likely due to changes in regulation rather than in the sequence and structure of the encoded protein.

Associated factors in 1611 cases of brachial plexus injury.

OBJECTIVE: To identify risk factors associated with brachial plexus injury in a large population. METHODS: A computerized data set containing records from hospital discharge summaries of mothers and infants and birth certificates was examined. The deliveries took place in more than 300 civilian acute care hospitals in California between January 1, 1994, and December 31, 1995. Cases of brachial plexus injury were evaluated for additional diagnoses and procedures of pregnancy, such as mode of delivery, gestational diabetes, and shoulder dystocia. Those complications were stratified by birth weight and analyzed, using bivariate and multivariate techniques to identify specific risk factors. RESULTS: Among 1,094,298 women who delivered during the 2 years, 1611 (0.15%) had diagnoses of brachial plexus injury. The frequency of diagnosis increased with the addition of gestational diabetes (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.7, 2.1), forceps delivery (OR 3.4, 95% CI 2.7, 4.3), vacuum extraction (OR 2.7, 95% CI 2.4, 3.1), and shoulder dystocia (OR 76.1, 95% CI 69, 84). In cases of brachial plexus injury, the frequency of shoulder dystocia increased from 22%, when birth weight ranged between 2.5 and 3.5 kg, to 74%, when birth weight exceeded 4.5 kg. The frequency of diagnosis of other malpresentation (nonbreech) (OR 73.6, 95% CI 66, 83) was increased for all birth weight categories. Severe (OR 13.6, 95% CI 8.3, 22.5) and mild (OR 6.3, 95% CI 3.9, 10.1) birth asphyxia were increased. Prematurity (OR 0.8, 95% CI 0.67, 0.98) and fetal growth restriction (OR 0.1, 95% CI 0.03, 0.40) were protective against brachial plexus injury. CONCLUSION: In macrosomic newborns, shoulder dystocia was associated with brachial plexus injury, but in low- and normal-weight infants, "other malpresentation" was diagnosed more frequently than shoulder dystocia. Our study findings suggest that brachial plexus injury has causes in addition to shoulder dystocia and might result from an abnormality during the antepartum or intrapartum period.

Childbearing beyond age 40: pregnancy outcome in 24,032 cases.

OBJECTIVE: To examine pregnancy outcomes in women age 40 or older. METHODS: We used data from the California Health Information for Policy Project, which consists of linked records from the birth certificate and the hospital discharge record of both mother and newborn of all births that occurred in acute care civilian hospitals in California between January 1, 1992, and December 31, 1993. The study population consisted of all women who delivered at age 40 or over. The control population was women who delivered between age 20 and 29 years during this 2-year period. We reviewed gestational age at delivery, birth weight, mode and type of delivery, discharge summary and birth certificate demographics, birth outcome, pregnancy, and delivery data. RESULTS: Approximately 1,160,000 women delivered during the study period, and 24,032 (2%) of these women were age 40 or older. Of this latter group, 4777 (20%) were nulliparous. The cesarean delivery rate for nulliparous women in the study population was 47.0%, and the rate for multiparous patients in this group was 29.6%. The cesarean delivery rate was 22.5% for nulliparous and 17.8% for multiparous women in the control group. In the older group, the operative vaginal delivery rate (forceps and vacuum) was 14.2% for nulliparous women and 6.3% for multiparous women. Rates of birth asphyxia, fetal growth restriction, malpresentation, and gestational diabetes were significantly higher among older nulliparas (6, 2.5, 11, and 7%, respectively) compared with rates among control nulliparas (4, 1.4, 6, and 1.7%, respectively), and there were similar significant increases among older multiparas (3.4, 1.4, 6.9, and 7.8%, respectively), compared with younger multiparous controls (2.4, 1, 3.7, and 1.6%, respectively). Mean (+/- standard error) birth weight of infants delivered by older nulliparous women was 3201+/-10 g, significantly lower than that among nulliparous controls (3317+/-1 g), whereas mean birth weight in the group of older multiparas (3381+/-5 g) was no different than that among younger multiparous controls (3387+/-1 g). Gestational age at delivery was significantly lower among older nulliparas (273.4+/-0.4 days), compared with nulliparous controls (278.5+/-0.05 days), and similarly lower among older multiparous women (274.0+/-0.2 days), compared with multiparous controls (278.3+/-0.05 days). More white women age 40 or over than younger white women were having a first child (64 and 39%, respectively). CONCLUSION: Nulliparous women age 40 or over have a higher risk of operative delivery (cesarean, forceps, and vacuum deliveries: 61%) than do younger nulliparous women (35%). This increase occurs in spite of lower birth weight and gestational age and may be explained largely by the increase in other complications of pregnancy. The increased frequency at which white women are having their first child at age 40 or over may reflect career choices that involve delaying childbirth until the fifth decade of life. These data will allow us better to counsel patients about their pregnancy expectations and possible outcomes.

A proposed model for telemedicine to supplement the physician workforce in the USA.

Maldistribution of physicians is the norm in much of the USA. This paper explores the effect that the integration of telemedicine into the health system could have on physician workforce requirements in the USA. The analysis is based on preliminary evidence suggesting that telemedicine is an effective and efficient means of delivering a broad spectrum of health services to medically under-served rural and inner-city communities. While the emphasis here is on interactive, video-based telemedicine services, other telemedicine modalities, such as store-and-forward techniques and remote monitoring, are likely to have a parallel effect. As these new technologies become a normal part of health care, they will reshape the medical workforce and exert a profound influence on physician workforce requirements in the USA. This paper presents a potential model for this reshaped workforce that emphasizes an expanded role for mid-level health-care providers.

Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia.

The mechanism by which inactivating mutations of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) cause X-linked hypophosphatemia remains unknown. However, recent reports suggest errant PHEX activity in osteoblasts may fail to inactivate a phosphaturic factor produced by these cells. To test this possibility, we examined coordinated maturational expression of PHEX and production of phosphate transport inhibitory activity in osteoblasts from normal and hyp-mice. We assessed the inhibitory activity in conditioned medium by examining the effects on opossum kidney cell phosphate transport and osteoblast PHEX expression by reverse transcriptase-polymerase chain reaction during a 17-day maturational period. Inhibitory activity increased as a function of osteoblast maturational stage, with no activity after 3 days and persistent activity by 6 days of culture. More significantly, equal phosphate transport inhibitory activity in conditioned medium from normal and hyp-mouse osteoblasts (control 1.90 +/- 0.12, normal 1.48 +/- 0.10, hyp 1.45 +/- 0.04 nmol/mg of protein/minute) was observed at 6 days. However, by 10 days hyp-mouse osteoblasts exhibited greater inhibitory activity than controls, and by 17 days the difference in phosphate transport inhibition maximized (control 2.08 +/- 0.09, normal 1.88 +/- 0.06, hyp 1.58 +/- 0.06 nmol/mg of protein/minute). Concurrently, we observed absent PHEX expression in normal osteoblasts after 3 days, limited production at 6 days, and significant production by day 10 of culture, while hyp-mouse osteoblasts exhibited limited PHEX activity secondary to an inactivating mutation. The data suggest that the presence of inactivating PHEX mutations results in the enhanced renal phosphate transport inhibitory activity exhibited by hyp-mouse osteoblasts.

Intrinsic mineralization defect in Hyp mouse osteoblasts.

X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3' Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb-Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37 +/- 6 vs. 1,484 +/- 68 counts . min-1 . microgram protein-1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits mineralization of extracellular matrix in vitro.

Shoulder dystocia and associated risk factors with macrosomic infants born in California.

OBJECTIVE: The purpose of this study was to examine the 1-year incidence statewide in California of shoulder dystocia and its associated risk factors. STUDY DESIGN: With a data set that contains computer-linked records from the birth certificate and hospital discharge records of both mother and baby, all births of infants >3500 g in >300 civilian acute care hospitals in California in 1992 were analyzed. All cases of shoulder dystocia were identified from discharge records, birth certificates, or both and were analyzed with both bivariate and multivariate techniques to identify specific risk factors. RESULTS: A total of 175,886 vaginal births of infants >3500 g were included in our database, of which 6238 infants (3%) had shoulder dystocia. The percentages of births complicated by shoulder dystocia for unassisted births not complicated by diabetes were 5.2% for infants 4000 to 4250 g, 9.1% for those 4250 to 4500 g, 14.3% for 4500 to 4750, and 21.1% for those 4750 to 5000 g. Shoulder dystocia increased by approximately 35% to 45% in vacuum- or forceps-assisted births to nondiabetic mothers. Similar increases were seen in unassisted births to diabetic mothers. The risk of shoulder dystocia for assisted births to diabetic mothers was even more dramatic: 12.2% for infants 4000 to 4250 g, 16.7% for those 4250 to 4500 g, 27.3% for those 4500 to 4750 g, and 34.8% for those 4750 to 5000 g. After controlling for other parameters, there was an increased risk of shoulder dystocia associated with diabetes (odds ratio 1.7), assisted delivery (odds ratio 1.9), and induction of labor (odds ratio 1.3). Rates of birth trauma, asphyxia, and length of stay were all increased among births complicated by shoulder dystocia. CONCLUSION: This information on the incidence of shoulder dystocia and associated risk factors for a large statewide population may assist providers of obstetric care in counseling patients when macrosomia is suspected. The inaccuracy of estimating fetal weight is a severe limitation in attempting to establish guidelines designed to prevent shoulder dystocia.

Patient satisfaction with telemedicine consultation in primary care: comparison of ratings of medical and mental health applications.

OBJECTIVE: To assess the viability of telemedicine as a vehicle for offering mental health consultations to primary-care patients. METHODS: Satisfaction ratings from 34 mental health encounters were compared with ratings from a convenience sample of 59 non-mental health encounters on four aspects of satisfaction: self-reported ability to speak freely; probability of further use of telemedicine; perceived experience of telemedicine personnel; and relative preference for a telemedicine visit compared with a face-to-face visit. The study was conducted in the context of the Telemedicine Program at the University of California, Davis. RESULTS: No significant differences in satisfaction were found between mental health and non-mental health encounter groups for any of the four aspects of satisfaction. CONCLUSIONS: Ratings from patients receiving mental health consultation using telemedicine yielded levels of satisfaction similar to those found in telemedicine consultations in non-mental health medical areas. The results support telemedicine as a means to extend mental health consultation to rural primary-care patients.

Is size discordancy an indication for delivery of preterm twins?

OBJECTIVE: Our goal was to determine the clinical significance of size discordancy in preterm twins. STUDY DESIGN: A retrospective study was performed to review outcomes of twins delivered between Jan. 1, 1988, and June 30, 1995. Maternal and neonatal records were assessed for demographic data, maternal medical history, and neonatal mortality and morbidity outcomes. Discordancy was defined as > or = 20% difference in birth weight. The chi 2 analysis was performed. RESULTS: There were 42 sets of discordant twins and 77 sets of concordant twins in the final analysis. The distribution of gestational ages in both groups was similar. We found no difference in maternal morbidity between the groups. Discordant sets had a significantly longer hospital stay (p = 0.003) and more cases of hyperbilirubinemia (p = 0.01), but there were no other differences in morbid outcomes. There were no differences in outcome variables between the two twins within discordant sets with respect to gender, size, birth order, growth restriction, or route of delivery. There were no stillbirths among any of the 238 infants. Of the 15 neonatal deaths, none occurred in infants delivered after 32 weeks' gestation or in infants weighing > 2000 gm at birth. Infants who were small for gestational age had a higher incidence of sepsis (p = 0.043) and longer hospital stays (p = 0.005) compared with infants who were appropriate for gestational age. CONCLUSIONS: Size discordancy alone does not appear to be an indication for preterm delivery of twins. When results of antenatal testing are normal and growth restriction is absent, attempts should be made to achieve a gestational age > 32 weeks and weight > 2000 gm before delivery is considered.

Vital statistics linked birth/infant death and hospital discharge record linkage for epidemiological studies.

A methodology for linking vital statistics linked birth/death data and hospital discharge data is described. The resulting data set combines information on a neonate's sociodemographic characteristics, prenatal care, and mortality aspects and connects it to detailed health outcome and resource utilization data, thus establishing an extensive database for epidemiological studies. In the absence of a universal identifier common to both databases, our linkage strategy relied on using a virtual identifier based on variables common to both data sets. In the case of multiple incidences of the same virtual identifier we used secondary health status information to optimize the likelihood of linking low birth weight or premature infants in one database to infants of similar health status in the other while randomizing cases in which no secondary information was present. Applying our method to the 1992 California birth cohort, we could link 563,114 out of 571,189 eligible births (98.59%). Of these links, 91.2% were established on the basis of unique virtual identifiers. The link was internally consistent and no bias was evident when comparing variable distributions for all single live births in the vital statistics linked birth/death file and linked births in the linked vital statistics linked birth/death and hospital discharge file. Multiple imputation techniques showed that the prediction error incurred by randomization was negligible. Even though computationally intensive, our method for linking the vital statistics linked birth/death file and the hospital discharge file appeared to be effective. However, it is important to be aware of the limitations of the resulting data set, in particular the fact that it cannot be used for tracking individual cases. The method provides a database suitable for a variety of perinatal epidemiological analyses, such as descriptive studies of disease distribution in neonates, studies of the geographic distribution of disease, and studies of the relationship between risk and outcome.

Phosphate transport in renal cell cultures of gy mice: evidence of a single defect in X-linked hypophosphatemia.

Although current theory holds that the murine homologs of X-linked hypophosphatemia represent mutations of two closely linked genes with distinct pathophysiological consequences, insufficient data are available to support this hypothesis. We investigated whether an intrinsic defect in renal sodium (Na+)-dependent Pi cotransport truly distinguishes gy from hyp mice. We compared Pi transport in immortalized cells from S1 and S2 segments of the renal proximal convoluted tubule (PCT) of normal and gy mice. Cells from both murine models exhibit characteristics of differentiated PCT cells including gluconeogenesis, alkaline phosphatase activity, and parathyroid hormone (PTH)- and thyrocalcitonin (TCT)-dependent adenosine 3',5'-cyclic monophosphate production. More importantly, kinetic studies reveal that cells from the PCT of gy mice have intrinsically normal Pi transport and support the hypothesis that, as in hyp mice, a humoral abnormality is likely responsible for the renal Pi wasting in this mouse model. These observations are consistent with the conclusion that gy and hyp mice do not represent mutations of two closely linked genes but rather two separate mutations of the same gene.

Family physician perception of economic incentives for the provision of office procedures.

BACKGROUND AND OBJECTIVES: The influence of capitation versus fee-for-service reimbursement for services provided by primary care physicians is an important topic as capitation becomes increasingly prevalent. This study ascertained whether family physicians perceive an economic incentive to perform flexible sigmoidoscopy, colposcopy, and vasectomy under capitated versus fee-for-service payment structures. METHODS: In May 1995, questionnaires were mailed to 592 randomly selected physician "diplomates" of the American Board of Family Practice in California, Florida, Texas, Virginia, and Minnesota. Nonrespondents received an additional mailing in July 1995. RESULTS: The return rate was 62%. Of 336 responses: 1) 177 (52%) provide flexible sigmoidoscopy; 68 (20%) think capitation and 173 (51%) think fee for service provide sufficient reimbursement to make this procedure profitable. 2) 69 (20%) provide colposcopy; 50 (16%) think capitation and 99 (30%) think fee for service provide sufficient reimbursement to make this procedure profitable. 3) 91 (27%) provide flexible sigmoidoscopy; 36 (11%) think capitation and 84 (25%) think fee for service provide sufficient reimbursement to make this procedure profitable. CONCLUSIONS: A significant number of family physicians provide these three procedures in their offices. Most physicians view fee-for-service payment as providing an economic incentive to provide these procedures. Capitation was less frequently perceived as providing sufficient reimbursement to make the provision of these procedures profitable.