Linking landscape-scale conservation to regional and continental outcomes for a migratory species.

Land-use intensification on arable land is expanding and posing a threat to biodiversity and ecosystem services worldwide. We develop methods to link funding for avian breeding habitat conservation and management at landscape scales to equilibrium abundance of a migratory species at the continental scale. We apply this novel approach to a harvested bird valued by birders and hunters in North America, the northern pintail duck (Anas acuta), a species well below its population goal. Based on empirical observations from 2007-2016, habitat conservation investments for waterfowl cost $313 M and affected <2% of the pintail's primary breeding area in the Prairie Pothole Region of Canada. Realistic scenarios for harvest and habitat conservation costing an estimated $588 M (2016 USD) led to predicted pintail population sizes <3 M when assuming average parameter values. Accounting for parameter uncertainty, converting 70-100% of these croplands to idle grassland (cost: $35.7B-50B) is required to achieve the continental population goal of 4 M individuals under the current harvest policy. Using our work as a starting point, we propose continued development of modeling approaches that link conservation funding, habitat delivery, and population response to better integrate conservation efforts and harvest management of economically important migratory species.

Kinetics of chimerism during the early post-transplant period in pediatric patients with malignant and non-malignant hematologic disorders: implications for timely detection of engraftment, graft failure and rejection.

The monitoring of chimerism by PCR has become a routine diagnostic approach in patients after allogeneic bone marrow or peripheral blood stem cell transplantation. Nevertheless, a temporal correlation between molecular and hematologic assessment of engraftment has not been clearly established. To address this issue, and to determine the potential clinical implications of early kinetics of mixed chimerism, we have investigated 66 allogeneic stem cell transplantations (SCTs) in 58 pediatric patients suffering from different types of leukemia (n = 44) or non-malignant hematologic disorders (n = 14) by close molecular monitoring during the first days and weeks after transplantation. Patient- and donor-derived hematopoiesis were assessed at 1- to 3-day intervals in peripheral blood samples by PCR analysis of highly polymorphic microsatellite loci (STR-PCR). Detection of an increasing, and ultimately dominant donor-specific allelic pattern, which we defined as molecular engraftment, preceded hematologic engraftment by a median of 7 days (range 1-17 days) in all patients investigated. PCR analyses during the first days after transplantation facilitated detection of molecular engraftment according to the above definition by day +14 (range day +2 to day +14), thus permitting prediction of successful engraftment (upper limit of the two-sided confidence interval po = 6%) while the peripheral leukocyte counts were mostly below 200/microl. In three cases, however, the criteria for molecular engraftment were not fulfilled by day +14. These patients also failed to show hematologic engraftment, and required a second transplantation. Close monitoring by STR-PCR showed that graft rejection and autologous recovery can occur early and with very rapid dynamics. Molecular analysis of specific leukocyte subsets isolated by flow-sorting enabled sensitive assessment of changes in the pattern of chimerism which had escaped detection in assays using whole white blood cell (WBC) samples. This approach facilitated the identification of expanding or decreasing recipient cells, and permitted early detection of impending rejection or relapse. Moreover, monitoring of the dynamics of chimerism allowed rapid assessment of the response to therapy. Our observations provide support for the concept of initiating genotype analyses early after SCT and monitoring at rather short intervals to permit timely evaluation of clinically relevant processes, and to provide a basis for early implementation of treatment.

Flow cytometric monitoring of hematopoietic reconstitution in myeloablated patients following allogeneic transplantation.

BACKGROUND: We report a routine flow cytometric (FACS) approach to quantify circulating leukocytes (NC) in myeloablated patients before and during regeneration after allogeneic transplantation of either whole bone marrow (BM) or of highly purified (> 99%) blood-derived CD34(+) cells (PBSC). METHODS: Blood samples were analyzed daily between infusion of the transplant and hematopoietic reconstitution. Significant differences in the composition of NC types and CD34(+) cells were observed between the two CD34 sources. The detection threshold for NC was roughly 1 cell per w L blood. RESULTS: The cell nadir of < 100 NC/ microL was reached on Day +4 (BM) and on day 0 (PBSC), when unusual CD34(+) cells of recipient genotype were detected in all patients. They were not clonogenic, showed high CD34 expression, but were negative for CD45, CD38, CD33, CD50, HLA-DR and Stro-1. Between Days +5 and +16, the onset of hematopoietic reconstitution was clearly detectable in multi-parameter evaluation of the FACS data. This was a median of 3.5 days before NC increased above 200/ w L blood and 4-10 days before granulocyte counts were > 500/ microL. It was marked by the appearance of monocytes, immature (CD38(+)) granulocytes, and clonogenic donor CD34(+) cells exhibited normal size and phenotype. DISCUSSION: We conclude that dynamic FACS analyses can reliably detect hematopoietic reconstitution, but also graft rejection, before a visible increase NC numbers. This may have considerable impact on clinical management strategies.

Cardiac patient air medical transport in the northeast region of the United States.

OBJECTIVES: 1) To develop and analyze a database of cardiac patient demographics and transport variables in the northeast region of the United States, and 2) to develop skills to enable future collaborative research in this region. METHOD: A retrospective review of air transport medical records was performed by flight crew members from five independent air medical transport programs. Parameters describing age, gender, cardiac diagnosis, referral patterns, hemodynamic parameters, medication infusions, arrhythmias, and invasive procedures were included. RESULTS: Data for 1,320 cardiac patients over the age of 30 years were compiled. Seventy percent were male, 30% were female, and the mean age was 60.7 years. The median flight time was 13 minutes. Seventy-three percent had a referring agency diagnosis of acute myocardial infarction. Transport originated from an emergency department 49% of the time and from an intensive care unit 51% of the time. Twenty percent of the patients had a heart rhythm other than normal sinus rhythm during transport. Twenty-eight patients had ventricular arrhythmias in flight (2%) and 28 patients suffered cardiac arrests (2%). Cardiogenic shock was observed in 13% of the patients. Twenty percent of the patients were endotracheally intubated. CONCLUSIONS: A database of patients transported by air for cardiac diagnoses was successfully established. Acute myocardial ischemia was the major indication for air transport. A region of flight programs collaborating on a research project can generate a large pool of subjects for analysis. Limitations of the methodology were identified and future research goals were better defined.

Evidence for a novel gene for familial febrile convulsions, FEB2, linked to chromosome 19p in an extended family from the Midwest.

Febrile convulsions are a common form of childhood seizure. It is estimated that between 2 and 5% of children will have a febrile convulsion before the age of 5. It has long been recognized that there is a significant genetic component for susceptibility to this type of seizure. Wallace, Berkovic and co-workers recently reported linkage of a putative autosomal dominant febrile convulsion gene to chromosome 8q13-21. We report here another autosomal dominant febrile convulsion locus on chromosome 19p. Linkage analysis in this large multi-generational family gave a maximum pairwise lod score of 4.52 with marker Mfd120 at locus D19S177. Linkage to the chromosome 8 locus was excluded in this family. Haplotype analysis using both affected and unaffected family members indicates that this febrile convulsion gene, which we call FEB2 , can be localized to an 11.7 cM, 1-2 Mb section of chromosome 19p13.3, between loci D19S591 and D19S395.

Familial cerebral cavernous angioma: a gene localized to a 15-cM interval on chromosome 7q.

Cerebral cavernous angiomas are collections of closely clustered vessels without intervening normal brain parenchyma, with microscopic evidence of hemorrhage, frequently multiple; they are best visualized with magnetic resonance imaging. Familial cerebral cavernous angioma occurs as an autosomal dominant disorder, although carriers of the gene are often asymptomatic. Recently, a gene responsible for familial cerebral cavernous angioma in a large Hispanic kindred was mapped to human chromosome 7q11-22, representing a large segment of DNA containing approximately 33 cM (about 33 million base pairs). This distance did not allow more restricted isolation of the region containing the familial cerebral cavernous angioma gene. In this report, we present a large white kindred with familial cerebral cavernous angioma and confirm the mapping to 7q11-22, including the genetic markers D7S558/D7S1789 and D7S804. Recombination between several markers in the region suggests that the candidate region is distal to D7S804. Combining our results with those previously published, we suggest that the gene is likely to reside within a 15-cM region bounded by markers D7S660 and D7S558/D7S1789. These results should assist the further refinement of the candidate region for familial cerebral cavernous angioma and facilitate the search for the gene.

Sets of short tandem repeat polymorphisms for efficient linkage screening of the human genome.

For the purpose of initial screening of the human genome in linkage mapping, two overlapping sets of high quality short tandem repeat polymorphisms (STRPs) which span the autosomes have been assembled. The higher density set contains a total of 363 markers with an average heterozygosity of 79% and an average sex-equal genetic distance between markers of 10.5 cM. The lower density set, which is a subset of the other, contains 156 markers with an average heterozygosity of 80% and an average spacing of 26.5 cM. Tri- and tetranucleotide STRPs comprised 47 and 63%, respectively, of the markers within the higher and lower density sets. Markers within the screening sets were selected to have maximum quality, where quality was defined as a blend of high informativeness, strong amplification under standard PCR conditions, low amplification background, and ease in scoring. The screening sets along with combinations of STRPs which can be amplified and electrophoresed simultaneously are available electronically through anonymous ftp.

A gene responsible for cavernous malformations of the brain maps to chromosome 7q.

Cavernous malformations of the brain are vascular lesions which are present in up to 0.4% of all individuals and which are often accompanied by seizures, migraine, hemorrhage and other neurologic problems. Using linkage analysis and a set of short tandem repeat polymorphisms, a gene responsible for cavernous malformations in a large Hispanic kindred was mapped to the q11-q22 region of chromosome 7. A maximum pairwise lod score of 4.2 was obtained at zero recombination with marker PY5-18 at locus D7S804. Lod scores in excess of 3.0 were obtained with four additional markers closely linked to PY5-18. A broad chromosome 7q haplotype of 33 cM length on the sex average map was shared by all affected individuals indicating that the gene lies between loci D7S502 and D7S479.

Rapid loss of vertebral mineral density after renal transplantation.

BACKGROUND: Osteopenia is a major complication of renal transplantation. Immunosuppressive regimens including cyclosporine, which permit the use of lower doses of glucocorticoids, may reduce glucocorticoid-induced osteopenia. METHODS: We prospectively studied the magnitude, distribution, and mechanism of bone loss in 20 adults who received renal allografts from living related donors, who had good renal function, and who were treated with azathioprine, cyclosporine, and low doses of prednisone. We measured serum biochemical markers of bone metabolism, determined the bone mineral density of the second, third, and fourth lumbar vertebrae and the shaft of the radius, and analyzed the histomorphometric features of iliac bone at the time of transplantation and six months later. Measurements of vertebral mineral density were repeated 18 months after transplantation in 17 of the patients. RESULTS: After transplantation, the mean serum concentrations of parathyroid hormone, phosphorus, and alkaline phosphatase decreased and the serum calcitriol concentration increased. The mean (+/- SD) bone mineral density of the vertebrae had decreased 6.8 +/- 5.6 percent 6 months after transplantation (P less than 0.05) and 8.8 +/- 7.0 percent 18 months after transplantation. In contrast, the bone mineral density of the radius had increased six months after transplantation (P less than 0.05). The histomorphometric studies showed that the rate of bone formation decreased from 50.5 +/- 44.8 to 23.1 +/- 13.8 microns3 per square micrometer per year (P less than 0.05), and the formation period lengthened from 70 +/- 42 to 146 +/- 144 days (P less than 0.05). Consequently, the amount of bone replaced during a remodeling cycle diminished. CONCLUSIONS: Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids.

Mineral content of bone: measurement by energy subtraction digital chest radiography.

Several methods are presently available for measuring the mineral content of bone. Those in widespread use include dual-photon absorptiometry and quantitative CT. The feasibility of using dual-energy digital chest radiography for determination of the mineral content of posterior ribs on digital chest images was studied by using a prototype unit. The results showed a significant difference in the mineral density of the posterior ribs of control subjects and those of patients who had osteoporosis (251.1 +/- 36 mg Ca2+/cm2 of rib vs 158.8 +/- 48 mg Ca2+/cm2, p less than or equal to .01) and a close correlation with values obtained by dual-photon absorptiometry of the lumbar spine (r = .77). The results suggest that this technique can provide an accurate assessment of the presence or absence of osteoporosis.

Effects of ethylnitrosourea on the hatchability and survival of chicks.

1. Two experiments were carried out to study the effects of the mutagen ethylnitrosourea (ENU) at concentrations of 1.4 to 3 500 microgram in 0.3 ml of saline (experiment 1) and 585 to 1 170 microgram in 0.1 ml of saline (experiment 2) on hatching eggs of two breeds of fowls. Hatchability (experiment 1) and survival up to 7 d of age without food (experiment 2) were assessed. In experiment 1 the hens were fed on different diets prior to providing the hatching eggs. 2. The mutagen showed a non-linear effect upon the hatchability, higher doses being less effective than small doses. 3. In the majority of cases, female embryos were more sensitive to the effect of ENU then male. 4. The mortality after hatching was also affected by ENU; the chicks from treated eggs surviving without food better then controls.

Estimation of hydroxylysine in urine and serum of patients with chronic uremia.

Free hydroxylysine and hydroxylysing glycosides were separated from urine and serum extracts on cation exchange resin and assayed spectrophotometrically. The method in conjunction with gel filtration in Bio-Gel P2 allowed to separate from urine also polypeptide hydroxylysine and hydroxylysine bound in small molecules of neutral or acidic character. Glycosylgalactosylhydroxylysineand galactosylhydroxylysine were separated by partition and/or ion exchange chromatography. Patients with chronic renal insufficiency had elevated serum levels and urinary excretion of hydroxylysine glycosides with increased excretion of hydroxylysine bound in polypeptides and in small molecules of neutral or acidic character. The excretion of free hydroxylysine was often within normal limits. When compared to values found in normal growing subjects and in adult patients with increased bone turnover and normal renin function the urinary excretion of hydroxylysine glycosides in chronic uremia was more markedly increased than excretion of hydroxyproline polypeptides and total hydroxyproline.