Trait-specific processes of convergence and conservatism shape ecomorphological evolution in ground-dwelling squirrels.

Our understanding of mechanisms operating over deep timescales to shape phenotypic diversity often hinges on linking variation in one or few trait(s) to specific evolutionary processes. When distinct processes are capable of similar phenotypic signatures, however, identifying these drivers is difficult. We explored ecomorphological evolution across a radiation of ground-dwelling squirrels whose history includes convergence and constraint, two processes that can yield similar signatures of standing phenotypic diversity. Using four ecologically relevant trait datasets (body size, cranial, mandibular, and molariform tooth shape), we compared and contrasted variation, covariation, and disparity patterns in a new phylogenetic framework. Strong correlations existed between body size and two skull traits (allometry) and among skull traits themselves (integration). Inferred evolutionary modes were also concordant across traits (Ornstein-Uhlenbeck with two adaptive regimes). However, despite these broad similarities, we found divergent dynamics on the macroevolutionary landscape, with phenotypic disparity being differentially shaped by convergence and conservatism. Such among-trait heterogeneity in process (but not always pattern) reiterates the mosaic nature of morphological evolution, and suggests ground squirrel evolution is poorly captured by single process descriptors. Our results also highlight how use of single traits can bias macroevolutionary inference, affirming the importance of broader trait-bases in understanding phenotypic evolutionary dynamics.

Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3ß-hydroxysterol Δ(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials.

Pressure-induced hysteresis in the high spin [Formula: see text] low spin transition in bis(2,4-bis(pyridin-2-yl)thiazole) iron(II) tetrafluoroborate.

Studies of the spin transition behavior of the mononuclear compound [Fe(pythiaz)(2)](BF(4))(2) have been carried out under hydrostatic pressures up to 9.13 kbar in the 5-300 K temperature range. Under ambient pressure this compound exhibits an approximately half-step (incomplete) HS [Formula: see text] LS transition with T(1/2) = 146 K without any thermal hysteresis. At pressures up to 4.5 kbar the behavior remains similar but with an upward displacement of T(1/2) and a slight decrease in the residual high spin fraction at low T. Application of higher pressures resulted in an almost complete two-step spin transition with several unusual pressure effects. Along with the expected pressure dependence of T(1/2) the surprising appearance of hysteresis in the spin transition curves was observed. It is suggested that the likely origin of this unprecedented behavior is a pressure-induced structural change.

Risk management strategies following analysis of cataract negligence claims.

INTRODUCTION: Clinical governance and risk management is very important in today's clinical practice. Cataract surgery is one of the most common procedures performed in the NHS, with around 200,000 operations per year. In order to help minimise the frequency of negligence claims, we performed a collaborative study to analyse claims relating to cataract surgery, dealt with by the defence organisations of England, Scotland, Wales, and Northern Ireland. MATERIALS AND METHODS: All claims dealt with by the Medical Defence Union, the Medical Protection Society, and the Medical and Dental Defence Union of Scotland from January 1990 to December 1999, were analysed by three ophthalmologists with at least 5 years' speciality experience. Recurrent themes were identified and claims were grouped by major causative factor. The findings were discussed by a panel compromising the authors in conjunction with the defence unions and risk management strategies were designed. RESULTS: There were 96 claims within the 10- year period analysed. Of these, the largest group (52) pertained to claims that related to accepted complications of cataract surgery. The remainder comprised two groups: 'Medical Errors' (anaesthetic, surgeon, and biometry) and 'Other Claims' comprising subjective complaints, pain and poor visual outcome. A total of 16 claims had been settled by May 2002, 45 are ongoing and 35 have closed without settlement. CONCLUSIONS: The majority of claims pertained to well-recognised complications of cataract surgery. If these risks are adequately explained to the patient before surgery and if the care provided reaches a standard acceptable to a responsible body of professional opinion, all such claims should be defensible. Good visual outcome does not protect against litigation.

Exceptional record of mid-Pleistocene vertebrates helps differentiate climatic from anthropogenic ecosystem perturbations.

Mid-Pleistocene vertebrates in North America are scarce but important for recognizing the ecological effects of climatic change in the absence of humans. We report on a uniquely rich mid-Pleistocene vertebrate sequence from Porcupine Cave, Colorado, which records at least 127 species and the earliest appearances of 30 mammals and birds. By analyzing >20,000 mammal fossils in relation to modern species and independent climatic proxies, we determined how mammal communities reacted to presumed glacial-interglacial transitions between 1,000,000 and 600,000 years ago. We conclude that climatic warming primarily affected mammals of lower trophic and size categories, in contrast to documented human impacts on higher trophic and size categories historically. Despite changes in species composition and minor changes in small-mammal species richness evident at times of climatic change, overall structural stability of mammal communities persisted >600,000 years before human impacts.

Long term cryostorage of UC blood units: ability of the integral segment to confirm both identity and hematopoietic potential.

BACKGROUND: With the maturation of UC blood banking, cord blood (CB) units stored for years prior to use in transplantation present a new set of issues in clinical transplantation, including interval improvements in immune typing and confirmation of product identity and viability. A preliminary analysis of the transplants supported by the St Louis Cord Blood Bank, looking for an impact of length of CB storage time and transplant outcome was performed. We evaluated the utility of an integral segment containing an aliquot of cryopreserved product that has been exposed to the same post-processing storage conditions as the unit as a quality control tool for CB banking. METHODS: Engraftment and survival following unrelated donor UC blood transplant were evaluated based on length of CB product storage at the St Louis Cord Blood Bank. A strategy of routine testing of the contiguous segment for high-resolution HLA typing (also confirming identity) and CFU analysis was tested in 283 consecutive CB searches. Comparison between CB unit and contiguous segment viability and hematopoietic potential was performed on 30 research CB units that had been stored up to 5 years. RESULTS: There was no statistical difference in engraftment or survival following unrelated donor cord blood transplant employing units banked < 1 year or > 3 years. Confirmatory HLA typing, CFU and viability testing was successfully performed from the same segment as part of a strategy for product release evaluation. When comparing the segment with its corresponding CB unit, the total colony-forming units (CFU) measured in the two was similar (P = 0.51, paired t-test). Three research units purposely sabotaged by an overnight thaw and refreeze had no CFU growth, but viability as measured by Trypan was still 68-98%. DISCUSSION: No deterioration of hematopoietic potential has been detected with storage up to 5 years. The contiguous segment CFU is representative of the product, and thus is a useful tool for quality control and confirmation of product viability. Viability, as measured by Trypan blue dye exclusion may be falsely reassuring.

Medicolegal claims in vascular surgery.

BACKGROUND: Knowledge about medicolegal claims is important for risk management and clinical practice. This study presents the first comprehensive collated data for vascular surgical practice. METHOD: Details of claims notified to the National Health Service Litigation Authority (NHSLA) since its inception in 1995, and to the Medical Defence Union (MDU) from 1990-1999 were analysed. RESULTS: A total of 424 claims were notified--170 NHSLA and 254 MDU (176 from surgeons who described themselves as 'vascular' and 248 from 'general surgeons'). Varicose veins were the commonest condition involved (244 claims) and nerve damage was the most frequent complaint (76), followed by incorrect or unsatisfactory surgery (35), and damage to the femoral vein (16) or artery (13). Arterial claims (174) against vascular surgeons comprised 88% in the NHS but only 39% in private practice: 45 related to aortic grafting, 28 to other bypass grafts, and 36 alleged failure to recognise or treat ischaemia. CONCLUSIONS: The likely cause of many of these claims was failure to advise patients about potential risks and expected benefits. Recognition of the areas of highest risk, with improvements in communication and record keeping, may limit future claims.

Coagulation testing in pediatric blunt trauma patients.

OBJECTIVES: To determine the prevalence of abnormal coagulation studies and to identify variables associated with markedly elevated coagulation studies in children with blunt trauma. METHODS: We reviewed the medical records of all patients < 15 years old hospitalized at a Level 1 trauma center for either blunt head or torso trauma over a 4-year period. Data from each patient's emergency department (ED) presentation were abstracted. ED coagulation studies were defined prior to data analysis as elevated if the international normalized ratio (INR) was > or =1.2 or partial thromboplastin time (PTT) was > or =33.0 seconds and markedly elevated if the INR was > or =1.5 or PTT was > or =40 seconds. Variables associated with markedly elevated coagulation studies in a univariate analysis (P < 0.05) were entered into a backward elimination logistic regression analysis to identify variables independently associated with markedly elevated coagulation studies. RESULTS: A total of 1082 patients' records were reviewed, and the 830 (77%) patients with coagulation studies obtained composed the study population. Elevated coagulation studies were detected in 232 (28%) patients, and 49 (6%) of these were found to be markedly elevated. In the multivariate analysis, a GCS < or =13 (odds ratio [OR] 8.7, 95% confidence interval [CI] 4.3, 17.7), low systolic blood pressure (OR 4.0, 95% CI 1.6, 9.9), open/multiple bony fractures (OR 2.9, 95% CI 1.4, 6.2), and major tissue wounds (OR 2.8, 95% CI 1.4, 5.6) were independently associated with markedly elevated coagulation studies. CONCLUSION: Hospitalized pediatric blunt trauma patients frequently have minor elevations in ED coagulation studies. Marked elevations occur infrequently and are independently associated with a GCS < or =13, low systolic blood pressure, open/multiple bony fractures, and major tissue wounds.

Abdominal ultrasound examination in pregnant blunt trauma patients.

BACKGROUND: The ability of abdominal ultrasound to detect intraperitoneal fluid in the pregnant trauma patient has been questioned. METHODS: Pregnant blunt trauma patients admitted to a Level I trauma center during an 8-year period were reviewed. Ultrasound examinations were used to detect intraperitoneal fluid and considered positive if such fluid was identified. RESULTS: One hundred twenty-seven (61%) of 208 pregnant patients had abdominal ultrasound during initial evaluation in the emergency department. Seven patients had intra-abdominal injuries, and six had documented hemoperitoneum. Ultrasound identified intraperitoneal fluid in five of these six patients (sensitivity, 83%; 95% confidence interval, 36-100%). In the 120 patients without intra-abdominal injury, ultrasound was negative in 117 (specificity, 98%; 95% confidence interval, 93-100%). The three patients without intra-abdominal injury but with a positive ultrasound had the following: serous intraperitoneal fluid and no injuries at laparotomy (one) and uneventful clinical courses of observation (two). CONCLUSION: The sensitivity and specificity of abdominal ultrasonography in pregnant trauma patients is similar to that seen in nonpregnant patients. Occasional false negatives occur and a negative initial examination should not be used as conclusive evidence that intra-abdominal injury is not present. Ultrasound has the advantages of no radiation exposure.

Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers.

The stromal cell population in bone marrow has been the focus of much attention since it has been shown that this cell population can be expanded and differentiated into cells with the phenotype of bone, cartilage, muscle, stroma, neural, and fat cells. We evaluated umbilical cord blood (UCB) for the presence of these cells. From the mononuclear fraction of UCB, we demonstrated the presence of a subset of cells that have been maintained in continuous culture for more than 6 months (>10 passages). These adherent cell populations express adhesion molecules CD13+, CD29+, and CD44+, but not antigens of hematopoietic differentiation. Exposure of these cells to osteogenic agents resulted in an increase in expression of alkaline phosphatase and the appearance of hydroxyapatite nodules by Von Kossa staining. Incubation with adipogenic agents resulted in morphological change and staining with Oil Red O. In addition, when exposed to basic fibroblast growth factor and human epidermal growth factor the cells underwent changes consistent with cells of neural origin. These changes were demonstrated by a combination of immunofluorescent labeling and Western immunoblots for neural-specific markers. Thus, similar to what has been previously reported with bone marrow, cord blood contains a population of cells that can be expanded in culture and are able to express the phenotype of multiple lineages. Cord blood multilineage cells are slower to establish in culture, have a lower precursor frequency and a lower level of bone antigen expression, and lack constitutive expression of neural antigens when compared to bone marrow, suggesting a more primitive population. Cord blood may prove to be a new source of cells for cellular therapeutics for stromal, bone, and, potentially, neural repair.

Failure to replicate association between the gene for the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and IGE.

The gene for the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) was identified as a gene underlying a rare idiopathic partial epilepsy syndrome in humans, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In a recent study, one of four silent polymorphisms (594 C/T) in CHRNA4 showed association with the common subtypes of idiopathic generalised epilepsy (IGE). In the present study, three of these polymorphisms were investigated for association in 182 Caucasian patients with IGE, but not categorised by subtype. They were compared with 178 controls in a case/control study. Further analyses were performed using a family-based design. None of the three polymorphisms exhibited any association with IGE. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:814-816, 2000.

Re-vaccination of 421 children with a past history of an adverse vaccine reaction in a special immunisation service.

BACKGROUND: In Australia an adverse event following immunisation (AEFI), with the exception of anaphylaxis and encephalopathy, is no longer considered an absolute contraindication to continuing vaccination with the suspect vaccine. Despite these recommendations there is a paucity of information on the re-vaccination of such children. AIMS: To describe the re-vaccination of a large number of children with a past history of an AEFI. METHODS: A review of children attending special immunisation services in three Australian tertiary care paediatric centres. RESULTS: During the review 970 children attended of whom 469 had experienced a past AEFI. Of these, 293 had experienced minor while 176 children had experienced significant neurological or allergic reactions. The majority (421/469) were re-vaccinated, with only one child having a significant neurological event; this was transient and resolved spontaneously. CONCLUSIONS: Re-vaccination of children who have a past history of an AEFI appears safe. A special immunisation service should be part of a comprehensive immunisation programme.

No association found between polymorphisms in genes encoding mGluR7 and mGluR8 and idiopathic generalised epilepsy in a case control study.

The genes of two group III metabotropic glutamate receptors, mGluR7 and 8, are candidate susceptibility genes for epilepsy. The Tyr433Phe polymorphism of mGluR7 and a novel polymorphism in the mGluR8 gene located 29 bp after the termination codon (2756C/T) were investigated in case control association studies performed on DNA from more than 100 patients with idiopathic generalised epilepsy (IGE). No significant association was found with IGE for either polymorphism.

Vaccination of children following a previous hypotonic-hyporesponsive episode.

BACKGROUND: Hypotonic-hyporesponsive episodes (HHE) were once considered a contraindication to pertussis vaccination. METHODOLOGY: To evaluate the safety of further vaccination, chart review was conducted of 66 children who had experienced an HHE, and who were assessed in one of three special clinics in three capital city tertiary paediatric hospitals. Immediately prior to the HHE, 63 children had received whole-cell pertussis vaccine, three had received acellular pertussis vaccine. RESULTS: Sixty-four of the 66 children were vaccinated in the special clinic, 59 with pertussis-containing vaccines (55 acellular, four whole-cell), without serious adverse events. There were no HHE after these further vaccinations. CONCLUSIONS: Previously healthy children who experience HHE reactions can safely continue standard vaccination schedules.

Compliance with universal precautions among pediatric residents.

BACKGROUND: There are few data on the rate of compliance with universal precautions among pediatricians. We hypothesized that compliance in pediatrics would be poor because of the intrinsic difficulties in performing invasive procedures in small subjects. DESIGN: Prospective, observational study. SETTING: Tertiary care children's hospital. STUDY PARTICIPANTS: A convenience sample of pediatric house staff. MAIN OUTCOME MEASURES: Pediatric house staff members were observed while performing invasive procedures. Procedure type, number of attempts required, and patient's age and diagnosis were recorded. Degree of compliance with universal precautions was judged by means of Centers for Disease Control and Prevention guidelines. Comparisons between the compliant and noncompliant groups were analyzed by chi2 and 2-tailed t test. RESULTS: A total of 128 procedures performed by 43 house officers, 4 advanced medical students, and 3 chief residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were performed correctly according to universal precaution guidelines. Rate of compliance did not appear to be influenced by small patient size, as judged by the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years among those in whom universal precautions were properly used vs 4.9+/-5.4 years among patients in whom precaution guidelines were breached; P=.96). Moreover, the number of attempts required in compliant procedures (1.31+/-0.53) was almost identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally, compliance did not improve with advanced level of training. CONCLUSIONS: Failure of compliance among pediatricians has no apparent association with procedure difficulty, and compliance rates continue to be poor through the course of pediatric training. These findings underline the need for effective education concerning universal precautions throughout pediatric residency, and they suggest that such efforts will not be precluded by obstacles intrinsic to performing invasive procedures on young subjects.

Importance of preoperative training and maze difficulty in task performance following hippocampal damage in the gerbil.

A series of experiments was conducted to evaluate the effects of preoperative training on three variations of a spatial working memory task following ischemic damage to the hippocampus. A discrete trial, pair-run procedure in a standard T-maze apparatus was used. Ischemic and sham gerbils were tested on a Win/Shift, Win/Shift Delay (10 s), or Win/Stay task with or without preoperative training. Gerbils tested on the Win/Shift or Win/Shift Delay tasks did not exhibit improved performance as a result of pretraining. Ischemic gerbils in Win/Shift tasks exhibited working memory impairment with or without preoperative training. In contrast, pretraining was found to significantly improve the performance of gerbils tested in the Win/Stay task. Choice accuracy of pretrained ischemic gerbils was not significantly different from controls. These data suggest that preoperative training can influence performance, however the difficulty of the task and/or the amount of pretraining are important variables. The tendency for rodents to alternate makes the Win/Shift task ideal when extensive training or testing is not possible.

Cardiac arrhythmias in phenol face peeling: a suggested protocol for prevention.

Cardiac arrhythmias are a potential complication in phenol face peeling. A comprehensive review of the literature is presented here demonstrating its reported incidence, as well as the actions of phenol both locally and systemically. In addition to the conventional measures that are presently followed in chemical face peeling, we present further recommendations for the prevention of cardiac arrhythmias. These include maintaining the patient with a sufficient fluid load, forcing diuresis with furosemide, and using lidocaine hydrochloride as a prophylactic antiarrhythmic agent. These guidelines will help avoid serious and even lethal complications.