The upper limb of Paranthropus boisei from Ileret, Kenya.

Paranthropus boisei was first described in 1959 based on fossils from the Olduvai Gorge and now includes many fossils from Ethiopia to Malawi. Knowledge about its postcranial anatomy has remained elusive because, until recently, no postcranial remains could be reliably attributed to this taxon. Here, we report the first associated hand and upper limb skeleton (KNM-ER 47000) of P. boisei from 1.51 to 1.53 Ma sediments at Ileret, Kenya. While the fossils show a combination of primitive and derived traits, the overall anatomy is characterized by primitive traits that resemble those found in Australopithecus, including an oblique scapular spine, relatively long and curved ulna, lack of third metacarpal styloid process, gracile thumb metacarpal, and curved manual phalanges. Very thick cortical bone throughout the upper limb shows that P. boisei had great upper limb strength, supporting hypotheses that this species spent time climbing trees, although probably to a lesser extent than earlier australopiths. Hand anatomy shows that P. boisei, like earlier australopiths, was capable of the manual dexterity needed to create and use stone tools, but lacked the robust thumb of Homo erectus, which arguably reflects adaptations to the intensification of precision grips and tool use. KNM-ER 47000 provides conclusive evidence that early Pleistocene hominins diverged in postcranial and craniodental anatomy, supporting hypotheses of competitive displacement among these contemporaneous hominins.

Landscape scale heterogeneity in the East Turkana ecosystem during the Okote Member (1.56-1.38 Ma).

Placing the biological adaptations of Pleistocene hominins within a well-resolved ecological framework has been a longstanding goal of paleoanthropology. This effort, however, has been challenging due to the discontinuous nature of paleoecological data spanning many important periods in hominin evolution. Sediments from the Upper Burgi (1.98-1.87 Ma), KBS (1.87-1.56 Ma) and Okote (1.56-1.38 Ma) members of the Koobi Fora Formation at East Turkana in northern Kenya document an important time interval in the evolutionary history of the hominin genera Homo and Paranthropus. Although much attention has been paid to Upper Burgi and KBS member deposits, far less is known regarding the East Turkana paleoecosystem during Okote Member times. This study pairs spatially-resolved faunal abundance data with stable isotope geochemistry from mammalian enamel to investigate landscape-scale ecosystem variability during Okote Member times. We find that during this period 1) taxa within the East Turkana large mammal community were distributed heterogeneously across space, 2) the abundance of C3 and C4 vegetation varied between East Turkana subregions, and 3) the Karari subregion, an area with abundant evidence of hominin stone tool manufacture, had significantly more C3 vegetation than regions closer to the central axis of the Turkana Basin (i.e., Ileret and Koobi Fora). These findings indicate that the East Turkana paleoecosystem during the Okote Member was highly variable across space and provided a complex adaptive landscape for Pleistocene hominins.

Reducing the Effects of Ageing on Cognition with Therapeutic Intervention of an Oral Multi-Nutrient: The REACTION Pilot Trial Study Design.

BACKGROUND: Clinical benefits have been reported with a specific multinutrient intervention (Souvenaid) in Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease. The effects of Souvenaid in age-related cognitive decline are not established. OBJECTIVE: To assess the feasibility of using virtual assessments to study the effects of a multinutrient on cognitive ageing. DESIGN: This is a randomized, double-blind, placebo-controlled, parallel group virtual pilot trial performed over 6 months in a single-centre. Participants are randomly allocated (1:1) to receive the specific multinutrient (Souvenaid) or an isocaloric, same tasting, placebo. SETTING: Trial visits are done virtually using secure online video communication. PARTICIPANTS: English or Spanish speaking people aged 55-89 years from all ethnic groups and considered to have age-related cognitive decline are eligible. MEASUREMENTS: Neuropyschological tests are done at baseline and after 6 months of intervention. Participants are contacted monthly by telephone to monitor safety, assess motivation and promote compliance. The primary outcome is feasibility determined by assessing recruitment rate, recruitment time, adherence rate and retention rate. A comprehensive set of neuropyschological measures will provide a broad assessment of cognitive function, including verbal memory, processing speed, and attention and executive function. Self-reported questionnaires are used to assess quality of life. CONCLUSIONS: This pilot trial will provide data to guide inform selection of participants and outcome measures in future studies in age-related cognitive decline.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

In vivo water state measurements in breast cancer using broadband diffuse optical spectroscopy.

Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water; however, detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975 nm. The precise NIR peak's shape and position are highly sensitive to water molecular disposition. We introduce a bound water index (BWI) that quantifies shifts observed in tissue water absorption spectra measured by broadband diffuse optical spectroscopy (DOS). DOS quantitatively measures light absorption and scattering spectra and therefore reveals bound water spectral shifts. BWI as a water state index was validated by comparing broadband DOS to magnetic resonance spectroscopy, diffusion-weighted MRI and conductivity in bound water tissue phantoms. Non-invasive DOS measurements of malignant and normal breast tissues performed in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p < 0.0001) compared to normal tissues. BWI of breast cancer tissues inversely correlated with Nottingham-Bloom-Richardson histopathology scores. These results highlight broadband DOS sensitivity to molecular disposition of water and demonstrate the potential of BWI as a non-invasive in vivo index that correlates with tissue pathology.

Brain natriuretic peptide testing for angina in a rapid-access chest pain clinic.

BACKGROUND: Patients complaining of chest pain are frequently referred to secondary care, although the majority have pain of non-cardiac origin. AIM: To investigate whether B-type natriuretic peptide (BNP) levels are predictive of a diagnosis of non-cardiac pain. DESIGN: Cross-sectional study. METHODS: Consecutive patients (n = 296) presenting to a rapid-access chest pain clinic (RACPC) received the usual clinical assessment plus near-patient BNP testing, with the assessor blinded to the result. After clinical assessment (including exercise stress testing if clinically indicated), pain was diagnosed likely/definitely cardiac or non-cardiac. RESULTS: Median BNP was higher in those diagnosed with likely/definite cardiac chest pain (26.5 vs. 8 pg/ml) (p < 0.0001, Wilcoxon rank sum test). The odds ratio for cardiac pain in those with BNP <20 pg/ml was 0.25 (95%CI 0.14-0.47) (p < 0.0005); adjusting for age and sex reduced this to 0.41 (95%CI 0.20-0.83) (p = 0.01). The area under the curve (AUC) for the model including BNP, age and sex was 0.70. With BNP as a continuous variable, the AUC for the same model was 0.72. DISCUSSION: In typical patients presenting to a RACPC, those with a BNP < or =20 pg/ml were significantly less likely to be diagnosed with cardiac pain. Near-patient BNP testing may have a role as a 'rule out test' for angina in patients presenting to a RACPC.

The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer.

The CAG repeat in exon 1 of the androgen receptor (AR) genes has been postulated as both a susceptibility allele and phenotypic modifier in BRCA1-associated breast cancers. We have analysed this repeat in a set of 178 breast cancer cases who have been selected only for age of presentation at 65 years or less. No effect of repeat length on age of presentation was found and there was no association between repeat length and family history. In combination with the data from other workers, our findings suggest that the androgen receptor repeat does not act as a modifier gene or susceptibility locus outside the context of the hereditary breast/ovarian cancer syndrome.

Purification and cell-free translation of mRNA coding for a variant specific antigen from Trypanosoma brucei gambiense.

Messenger RNA (mRNA) coding for a variant specific surface antigen (VSA) from Trypanosoma brucei gambiense was isolated from total trypanosomal polyribosomes by indirect immunoprecipitation. An IgG fraction of antisera to purified VSA was obtained by ion exchange chromatography and Protein A-agarose affinity chromatography. These antibodies were then subjected to affinity chromatography on a VSA-agarose column to remove non-specific IgG. Polyribosomes from the same antigenic variant of T. b. gambiense were isolated from a cell lysate and those polysomes bearing nascent VSA were bound to the IgG by gentle mixing and the complexes formed were retrieved by precipitation with fixed Staphylococcus aureus cells. The VSA-specific mRNA was separated from these complexes by dissociation of the polysomes, deproteinization, and affinity chromatography on oligo(dT)-cellulose. The mRNA isolated in this way was shown to be undegraded, active in protein synthesis and homogeneous electrophoretically. The products of the cell-free translation of this mRNA were precipitable by specific IgG but not by antiserum to a heterologous VSA. The translation product was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel exclusion chromatography. The molecular weight of the mRNA was measured by electron microscopy, agarose and polyacrylamide gel electrophoresis. Enough highly purified mRNA can be isolated in this manner to be used for hybridization analysis of the VSA gene(s).

Intraocular pressure of rhesus monkey (Macaca mulatta). I. An initial survey of two free-breeding colonies.

As part of an ophthalmic and anthropometric survey of two free-breeding rhesus monkey (Macaca mulatta) populations, intraocular pressure (IOP) of 114 animals was measured under ketamine catalepsia with the use of a floating-tip pneumatonometer. The mean IOP of the 102 animals included in the main analyses was 14.9 +/- 2.1 (S.D.) mm Hg. The age distribution of animals in this sample ranged from 7 months to 21 years and reflected reasonably well the estimated age distribution in the total population (approximately 1600 macaques). Since ketamine does not have a barbiturate-like effect on IOP, this value can be regarded as a good estimate of the normal IOP of rhesus monkeys. No significant differences were found between left and right eyes nor between males and females. However, the mean IOP of infants and juveniles (7 months to 3 years) was significantly higher (15.7 +/- 2.0 mm Hg; n = 33) than that of young adult and adult rhesus monkeys (14.5 +/- 2.0; n = 69). The IOP of young animals (less than or equal to 6 years) showed a decline between 9 A.M. and 2 P.M., whereas the IOPs of older animals showed only small fluctuations between 8 A.M. and 5 P.M. This study shows that the normal IOP of macaques is remarkably similar to that of humans and demonstrates the fesibility of surveying IOP in free-ranging primates.

ThinPrep Processor. Clinical trials demonstrate an increased detection rate of abnormal cervical cytologic specimens.

The authors compared the accuracy of conventionally prepared smears and smears prepared by an automated, fluid-based, thin-layer processing device in the detection of cytologic abnormalities. A total of 3218 patients from five centers took part in this study, in which a single cervical sample was split into a matched pair. The conventional smear was made in the routine fashion; the remainder of the cells on the sampling device were rinsed into a transport-fixation fluid. A slide was then prepared from the solution using the thin-layer processor. Diagnostic findings identified on the two preparations were compared in a blinded fashion, and a discrepancy resolution procedure was used to eliminate screening differences. Overall, there was a high correlation in the diagnoses of the two methods. For low-grade or more severe disease, the thin-layer method resulted in a 13% increase in the rate of detection, as compared with the conventional Papanicolaou smear technique.

Tuberculin screening of trauma admissions at a university hospital. A preventive strategy.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection in our trauma service population, namely, those patients who had positive Mantoux (purified protein derivative [PPD] [tuberculin]) tests. DESIGN: Prospective study. SETTING: Trauma service at a university hospital in Newark, NJ. PATIENTS AND METHODS: During a 9-month period, 110 admitted trauma patients underwent screening for TB. Of these patients, 20 had undergone recent PPD tests in the last 6 months, of which nine were positive. The remaining 90 patients underwent PPD and delayed-type hypersensitivity skin tests (anergy panel); five patients were unavailable for follow-up. The patients also answered questions regarding human immunodeficiency virus status, risk factors for TB infection, and clinical symptoms. RESULTS: The mean age of the study group was 34 years (age range, 13 to 69 years). Eighty-four percent of these patients were males who belonged to the high-risk socioeconomic, racial, and ethnic groups (poor, non-white). The tests for 15 patients (17%) were newly discovered to be positive for PPD. Eleven percent of the patients with negative PPD tests were anergic, thus raising the percentage of patients with positive PPD tests to 20%. The human immunodeficiency virus status was known in only 41% of the total patients. All patients with positive PPD tests had a chest x-ray film performed; of these patients, positive findings for TB were determined for one patient. Another patient had evidence of abdominal TB at laparotomy. All patients with positive PPD tests were given appointments in the pulmonary clinic for follow-up, and only three of 15 patients kept their appointments. CONCLUSIONS: Patients who were admitted to the trauma service were predominantly young males from high-risk groups with a high incidence of TB infection. Their admission to the trauma service was a unique opportunity for screening and implementing existing preventive programs.

Derivation of highly mefloquine-resistant lines from Plasmodium falciparum in vitro.

Serial passage of a multidrug-resistant clone of Plasmodium falciparum in concentrations of mefloquine hydrochloride ranging from 30 to 2,400 ng/ml resulted in the derivation of increasingly resistant parasite lines in vitro. Parasite lines isolated in mefloquine concentrations greater than 300 ng/ml demonstrated increased vacuolization, enhanced pigment production, and increased growth rates as compared with the progenitor clone, W2-mef. Although microdilution incorporation assays demonstrated that the 50% inhibitory concentration (IC50) of mefloquine were similar for all lines, the IC90, IC95, and IC99 levels were significantly increased. Growth rate assays performed in 5% hematocrit suspensions demonstrated different levels of mefloquine resistance among these lines. Under these conditions the most resistant line, Mef 2.4, grew efficiently in approximately 10-fold higher concentrations of mefloquine than the progenitor clone W2-mef. Analysis of drug susceptibility profiles to mefloquine hydrochloride, chloroquine diphosphate, quinine sulfate, and halofantrine hydrochloride indicated that selection for high levels of mefloquine resistance had resulted in significant increases in resistance to halofantrine and increased sensitivity to chloroquine. The phenotypic changes demonstrated in the most resistant line, Mef 2.4, reflect a multidrug resistant-like phenotype, and appear to mimic changes recently reported in drug susceptibility profiles of recrudescent isolates following mefloquine treatment failures in Thailand.

Comparison of water and lipid content measurements using diffuse optical spectroscopy and MRI in emulsion phantoms.

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35-94% and 63-6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650-1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI "gold standard" technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.

Pupil noise is a discriminator between narcoleptics and controls.

The pupil light reflex has a long history of being able to indicate states of mental arousal, ranging from sleepiness to concentrated cognitive effort. Such mental states have usually been inferred from pupil diameter or pupil area movements relative to some reference; sleepiness, for example, is characterized by a smaller than average pupil while mental effort brings on a slightly larger pupil. But all pupil movements and associated states of arousal are accompanied by a persistent random pupil diameter motion which has previously been attributed to neurological noise, the noise apparently arising in the neurological controller of the pupil reflex control system. Our experiments and signal processing methods show that the amplitude of this pupil noise is an indicator of the sleeping disorder narcolepsy. Narcoleptics are found to have diminished pupil noise amplitudes relative to control subjects. Pupil noise is estimated by statistical procedures which yield unbiased noise measures in the form of six-dimensional Gaussian vectors. Each subject is associated with a Gaussian vector which is optimally projected onto a scalar axis so as to maximize the mean square distance between the narcoleptic and control samples. The Kullback-Leibler discrimination function is estimated and then evaluated for each projection as a means of discriminating narcoleptics from controls. The projected noise measures correctly classify 18 out of 20 subjects. The projected values also form the basis for supporting or rejecting a hypothesis of narcoleptic or control class membership. Parametric and nonparametric hypothesis tests suggest that, with probabilities close to one, narcoleptics and controls are distinguishable classes. To emphasize the importance of pupil noise as a diagnostic tool we present evidence from the neurophysiology literature indicating that Alzheimer's disease and narcolepsy have some of the same brainstem nuclei implicated. Further, Alzheimer patients and narcoleptics share some of the same disturbed sleep patterns.

Differences in reported sleep need among adolescents.

Increased lifestyle demands and reduced sleep are reported to result in daytime sleepiness and impaired functioning for teenagers. A sample of 612 freshman urban high school students completed a questionnaire describing their sleep patterns and problems, along with sociodemographic information, daily activities, pubertal development, depressive mood, and morning-evening preference. About 63% of the respondents felt they needed more sleep on weeknights (MS group), experienced sleepiness that interfered with their schoolwork, and had problems with sleeping. The other group reported they got sufficient sleep on weeknights (SS group) and did not experience sleepiness problems to the same degree. However, both had similar weeknight sleep and daily activity patterns. The MS group reported an ideal sleep time of 9.2 h, about 2 h more than they were getting and 1 h more than the SS group ideal, and had a higher preference for later bed and waking times. In our sample, individual differences in biologic sleep need and quality of sleep may be emerging as early as 14 years of age.

Readability levels of selected hypercholesterolemia patient education literature.

OBJECTIVES: To assess the readability of selected hypercholesterolemia print materials, summarize the limitations of readability formulas, describe how expert judgement can be used to enhance readability determinations of printed materials, and discuss indirect and direct methods for assessing patient literacy levels. DESIGN: Descriptive, retrospective, convenience sample OUTCOME MEASURES: Readability of four AHA/NLHBI hypercholesterolemia patient education pamphlets by use of three readability formulas and the Reading Materials Checklist. RESULTS: The FOG, Fry, and SMOG formulas were used to calculate reading levels by two raters who independently applied the formulas to the same word passages chosen from the beginning, middle, and end of the pamphlets. The mean reading grade levels were 14.4, 15.8, 14, and 14.4, demonstrating that all four pamphlets were written for people with college level reading skills. The limitations of readability formulas such as variations in reading estimates were demonstrated. When expert judgement was applied with the Reading Materials Checklist, all pamphlets were found lacking in the areas of legibility, usability, and motivational appeal. CONCLUSIONS: The results indicate that the pamphlets may not be appropriate for use with most of the adults in the United States who may be candidates for hypercholesterolemia patient education. Because reading formulas are limited in the information they provide, expert judgement regarding readability of print materials should also be applied. Additionally, indirect and direct techniques need to be used to assess the literacy level of the patient population who will be using the printed materials.

Reliability and construct validity of alternate forms of the CLS Inventory.

Learning style assessment measures the preferences for specific ways of learning in selected teaching-learning situations. The Learning Styles Inventory, which was constructed based on the Canfield model of learning style, assesses learning preferences that focus on selected motivational and environmental factors present in formal instructional situations. The study presented here was designed to determine the reliability and construct validity of Canfield's ipsative inventory, and an alternate normative form developed by the authors. Results suggest that the alternate form is at least as reliable as the original ipsative inventory, with a factor structure that is congruent with the Canfield learning styles model.

The effect of drug therapy on the perceived symptom and ADL experiences of narcoleptics.

Medications for the treatment of narcolepsy consist of central nervous system (CNS) stimulants to control the somnolent symptoms and tricyclic antidepressants to control the rapid-eye-movement (REM) sleep related symptoms. Anecdotal information suggested that many narcoleptics perceive their symptoms, particularly their sleepiness, to be poorly controlled despite taking medication. This study was a secondary analysis which examined if drug therapy made a difference in the perceived symptom experience and ability to perform daily living activities (ADLs) as reported by narcoleptics. No significant association was found between CNS stimulant or tricyclic antidepressant drug therapy and the subjective ratings of narcoleptic symptoms, nor with the perceived ability to perform ADLs. While this study did not examine symptom ratings on and off drug therapy, these findings do suggest that narcoleptics may have to utilize behavioral strategies with their medication regimens to effectively cope with narcolepsy's adverse effects on daily life.

Measurement of functional ability in patients with coronary artery disease.

The purpose of this study was to examine measures of functional ability in a group (n = 60) of cardiac patients undergoing treadmill exercise tests. Functional ability was defined as the degree to which the individual is able to perform physical activity in the absence of symptoms. Instruments used were the Modified Harvard Alumni Scale (MHAS), the Symptom Scale (SS) comprised of the following subscales: angina (AS), shortness of breath (SOBS), and fatigue (FS); the overall Health Rating Index (OHRI); and the Goldman Specific Activity Scale (SAS). Concurrent validity was supported by the fact that the instruments were correlated with metabolic equivalents achieved on the treadmill. Correlations were: MHAS (r = .34, P < .01), SS (r = .67, p < .01), AS (r = .54, p < .01), SOBS (r = -.41, p < .05), FS (r = -.56, P < .001) and the OHRI (r = .45, p < .001). Reliability was determined using Cronbachs, alpha and were: SS = .92, AS = .87, SOBS = .86, FS = .85 and OHRI = .88. Findings support the need for testing and evaluation of instruments measuring functional ability in diverse cardiovascular populations.

An adolescent services plan to incorporate status offenders into the child welfare system.

A model plan is presented for adolescent services that would facilitate the current trend to shift troubled but nondelinquent youngsters from the juvenile justice system into the child welfare system.