Low bone turnover and low bone density in a cohort of adults with Down syndrome.

UNLABELLED: Increased incidence of osteoporosis in Down syndrome has been reported, but etiology is not established. We report low bone turnover markers and bone mineral density (BMD) in a cohort of people with Down syndrome without consistent clinical risk factors. Our results should guide future studies and treatments for this common problem. INTRODUCTION: To better understand the etiology for osteoporosis in Down syndrome (DS), we measured bone density by dual-energy X-ray absorptiometry (DXA) and circulating biochemical markers of bone formation and resorption in a cohort of 30 community-dwelling DS adults. METHODS: Seventeen males and 13 females followed in the University of Arkansas Down Syndrome Clinic were evaluated by DXA to estimate BMD and underwent phlebotomy to measure serum procollagen type-1 intact N-terminal propeptide (P1NP) to evaluate bone formation, and serum C-terminal peptide of type-I collagen (CTx) to evaluate bone resorption. RESULTS: Seven of 13 DS females and 12 of 17 DS males had low bone mass at one of measured sites (z≤-2.0). When data were grouped by age, males had apparent osteopenia earlier than females. The mean P1NP in the normal group was 19.2±5.2 ng/ml vs. 2.2±0.9 ng/ml in the DS group (P=0.002). Serum CTx levels in the normal group were 0.4±0.1 ng/ml vs. 0.3±0.1 ng/ml (P=0.369). CONCLUSIONS: Low BMD in adults with DS is correlated with a significant decrease in bone formation markers, compared to controls without DS, and is independent of gender. These data suggest that diminished osteoblastic bone formation and inadequate accrual of bone mass, with no significant differences in bone resorption, are responsible for the low bone mass in DS. These observations question the use of antiresorptive therapy in this population and focus attention on increasing bone mass by other interventions.

Reliability and validity of the Older Americans Resources and Services (OARS) social resources scale in six European countries.

OBJECTIVES: The purpose of this article is to examine data quality, reliability, and construct validity of the Older Americans Resources and Services social resources scale in six European countries (The Netherlands, Luxembourg, Italy, Austria, the United Kingdom, and Sweden). METHODS: A questionnaire was administered through face-to-face interviews in five countries, and postal interview in the sixth, to representative populations of adults aged 50 to 90 living independently (N = 12,478). This article examines missing values and distribution of items in the social resources scale, and consistency of skew and kurtosis across countries. We performed item-total correlations and ran confirmatory factor analyses to test a three-factor model obtained in previous U.S. and Spanish analyses. Cronbach's alpha determined the reliability of the factors. RESULTS: We observed a relatively large proportion of missing data for one item (have someone who would help you). All items correlated with a score equal to or greater than 0.20. Although the confirmatory factor analyses generally supported the acceptability of the three-factor structure in the European data, the reliability of two dimensions (dependability and affective) was unacceptably low. DISCUSSION: Differences across countries make it unlikely that researchers can develop a single social resources scale that would have item equivalence in multiple countries.

Changes in levels of social isolation and loneliness among older people in a rural area: a twenty-year longitudinal study.

The Bangor Longitudinal Study of Ageing (BLSA), conducted in rural Wales from 1979 to 1999, followed a cohort of survivors from more than 500 people over 20 years. Using both quantitative and qualitative data from the study, the factors associated with increases and decreases in loneliness and social isolation were identified. The study was based on a population sample and survivors were followed up every 4 years. From 1983 to 1987, 30 people aged 75 and over in 1979 were studied intensively. The customary measure of loneliness was used, as well as an aggregate measure devised by the research team. Social isolation was similarly measured, using an aggregate measure. Respondents were assessed as demonstrating low, moderate, or high levels of loneliness or isolation. Subsequently, statistical models of loneliness and social isolation were developed. Some respondents were assessed as not experiencing social isolation or loneliness during the study. Others showed changes in levels. In this article, the data are explored, seeking factors associated with changes in social isolation and loneliness. Outcome measures of these two variables of interest are compared with items from the aggregate measures and other identifiable intervening variables. The article discusses which change variables contribute most to levels of isolation and loneliness and result in different combinations of these two outcomes. Implications for policy and practice are discussed.

Effects of drugs of abuse and signal predictability in two models of sustained attention in pigeons.

The acute effects of ethanol, pentobarbital, D-amphetamine and nicotine were determined in two animal models of attention. This study examined if changing the predictability of the stimulus presentation modifies drug effects under two attention tasks, in male White Carneau pigeons. The first task was a continuous-trial sustained attention task. For seven pigeons, the frequency of signal presentation was constant and predictable, once every 60 s [a fixed-interval 60 s (FI-60) signal presentation]. For seven additional pigeons, the frequency of signal presentation averaged once every 60 s, but the interval between presentations was random and variable [a variable-interval 60 s (VI-60) signal presentation]. Following ethanol (0.3-3 g/kg) and pentobarbital (0.3-13 mg/kg), decreases in p(hit) and large increases in p(false alarm) occurred at doses that did not impair response rates. Following D-amphetamine (0.03-5.6 mg/kg) and nicotine (0.03-3 mg/kg), a significant decrease in p(hit) and increase in p(miss) occurred at doses that did not impair response rates. The second task was a discrete-trial attention task, under which eight pigeons were presented a constant and predictable signal and eight were presented a random and unpredictable signal. Following ethanol (0.3-3 g/kg) and pentobarbital (0.3-13 mg/kg), drug effects on accuracy occurred at doses that suppressed responding. The schedule of signal presentation did not alter the effects of ethanol or pentobarbital. Following D-amphetamine (0.03-5.6 mg/kg) and nicotine (0.03-3 mg/kg), a significant decrease in p(hit) and increase in p(error of omission) occurred at doses that did not impair response latencies, but there were no differences between pigeons responding under the predictable (FI-60) or variable (VI-60) signal presentations. The observation of differential drug effects [e.g. p(false alarms)] on performance under the continuous-trial procedure supports the validity of the procedure for measuring drug effects on attention. However, changes in signal predictability had little effect on control or drug conditions under this continuous-trial sustained attention procedure.

Using network variation in practice: identification of support network type.

This paper evaluates the use of a support network measurement instrument (PANT) in social work practice, focusing primarily on a study of the introduction and use of the instrument with social work teams. The paper describes practitioners' responses during the training period and during the initial phases of using the instrument in practice. The findings show how growth in familiarity with the new tool and support from managers overcame early resistance and contributed to both practitioners' confidence and understanding of the situations of older people. It allowed them to tailor interventions appropriately. It also contributed to understanding of differences between teams in the area and made it possible to create area profiles of older service users, their carers and their needs. The importance of network type for prediction of outcomes is stressed.

The experience of caring for older people with dementia in a rural area: using services.

This paper reports findings from the carer component of the Gwynedd Dementia Study. It is based on carer interviews, using quantitative and qualitative data. It confirms earlier findings that carers for people with dementia are typically female and older than other carers, although it notes that caring husbands are amongst the oldest carers. The problems that are most common are those that cause psychological stress to carers. Carers were found to receive both help and appreciation from their families and to perceive neighbours to be helpful if needed. In Gwynedd, as elsewhere, levels of formal service inputs are low, but most of the carers appeared to receive the services they needed. Problems are primarily associated with crisis support and long-term care is accepted reluctantly. It is suggested that community care dementia specialists could play a supporting role for carers.

The limited utility of the Mini-Mental State Examination in screening people over the age of 75 years for dementia in primary care.

The Mini-Mental State Examination (MMSE) is used worldwide to assess cognitive status and it has been recommended for use in primary care to detect dementia. In this study, the MMSE was administered during annual health checks for patients over 75 years of age in nine practices by a member of the primary care team. The mean age was 80 years. Of the 709 patients screened, 286 scored at or below the cut-off point, which was set at 26/30 on the MMSE, and they were invited to be assessed further by a researcher, using the well-validated GMS-AGECAT diagnostic system. Eighty-four of these patients refused, 173 were identified as not having dementia, and 29 (14%) were identified as having dementia. These results, with an 86% false-positive rate, raise concerns regarding the utility of the MMSE as a screening instrument for dementia in primary care.

Effects of repeated exposure to JP-8 jet fuel vapor on learning of simple and difficult operant tasks by rats.

Groups of 16 Sprague-Dawley rats each were exposed by whole-body inhalation methods to JP-8 jet fuel at the highest vapor concentration without formation of aerosol (1,000 +/- 10% mg/m3); to 50% of this concentration (500 +/- 10% mg/m3); or to treated room air (70 +/- 81 L/min) for 6 h/d, 5 d/wk, for 6 wk (180 h). Although two subjects died of apparent kidney complications during the study, no other change in the health status of exposed rats was observed, including rate of weight gain. Following a 65-d period of rest, rats were evaluated for their capacity to learn and perform a series of operant tasks. These tasks ranged in difficulty from learning of a simple food-reinforced lever pressing response, to learning a task in which subjects were required to emit up to four-response chains of pressing three different levers (e.g., press levers C, R, L, then C). It was shown that repeated exposure to 1,000 mg/m3 JP-8 vapor induced significant deficits in acquisition or performance of moderately difficult or difficult tasks, but not simple learning tasks, as compared to those animals exposed to 500 mg/m3. Learning/performance of complex tasks by the 500-mg/m3 exposure group generally exceeded the performance of control animals, while learning by the 1,000-mg/m3 group was nearly always inferior to controls, indicating possible "neurobehavioral" hormesis. These findings appear consistent with some previously reported data for operant performance following acute exposure to certain hydrocarbon constituents of JP-8 (i.e., toluene, xylenes). There has, however, been little previously published research demonstrating long-term learning effects for repeated hydrocarbon fuel exposures. Examination of regional brain tissues from vapor-exposed rats indicated significant changes in levels of dopamine in the cerebral cortex and DOPAC in the brainstem, measured as long as 180 d postexposure, as compared to controls.

Effects of drugs of abuse on response accuracy and bias under a delayed matching-to-sample procedure in squirrel monkeys.

The effects on memory of drugs of abuse from several pharmacological classes were examined in four adult male squirrel monkeys responding under a delayed matching-to-sample schedule of food presentation. Subjects were required to emit 20 responses on a sample key transilluminated by either a constant white or a flashing blue light. The twentieth response initiated a 3-second delay followed by presentation of two comparison stimuli. If a response was made to the key that matched the sample stimulus (correct match), a single food pellet (97 mg) was delivered. Pentobarbital (0.32-10 mg/kg), diazepam (0.1-5.6 mg/kg), phencyclidine (0.01-0.32 mg/kg) and cocaine (0.1-3.2 mg/kg) dose-dependently reduced accuracy of matching performance towards chance levels. Amphetamine (0.01-1.0 mg/kg) resulted in a small, but statistically significant, reduction in accuracy at a dose of 0.56 mg/kg, while 1.0 mg/kg completely suppressed responding. Analyses indicated that pentobarbital, diazepam and cocaine produced either position or color biases in responding, and in some cases these biases in responding were associated with decreases in accuracy. No such response biases were observed with phencyclidine or D-amphetamine. These results suggest that drug effects on working memory performance can, in some cases, be the result of non-mnemonic processes. Thus, they illustrate the importance of examining behavioral endpoints in addition to task accuracy when interpreting drug effects on working memory in laboratory animals.

Ageing without children: rural Wales.

This paper aims to identify the pathways and adaptations to childlessness. It is based on data for 65 childless men and women who took part in the Bangor Longitudinal Study of Ageing (1979-1999) and survived to at least 1987. Interviews were conducted mainly in the homes of the respondents at 4 yearly intervals and both qualitative and quantitative data were recorded. The paper distinguishes between men and women and between those who married and those who never-married. The findings demonstrate contrasting life styles between childless men and childless women. Never-married childless men tend to have been employed in solitary occupations or those based on an all male workforce and to rely on dependency relationships with female kin, while men who marry rely heavily on their wives. Never-married women in contrast tend to be more independent and outgoing and to have worked in jobs which brought them into frequent contact with people. Most childless women who married had not worked after marriage; they had close relationships with husbands and on widowhood adopted an independent, self-sufficient lifestyle. The findings demonstrate more positive adaptations to childlessness among women than men.

Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon.

OBJECTIVES: The pathological entity of primitive neuroectodermal tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of neoplasms on a clinical as well as on a molecular level. We evaluated the importance of DNA amplification in medulloblastomas and other primitive neuroectodermal tumours (PNETs) of the CNS. METHOD: Restriction landmark genomic scanning (RLGS), a method that allows the detection of low level amplification, was used. RLGS provides direct access to DNA sequences circumventing positional cloning efforts. Furthermore, we analysed several samples by CGH. DESIGN: Twenty primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma cell lines were studied. RESULTS: Although our analysis confirms that gene amplification is generally a rare event in childhood PNET/MB, we found a total of 17 DNA fragments that were amplified in seven different tumours. Cloning and sequencing of several of these fragments confirmed the previous finding of MYC amplification in the cell line D341 Med and identified novel DNA sequences amplified in PNET/MB. We describe for the first time amplification of the novel gene, NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not overexpressed in the tumours studied. We have determined that NAG maps less than 50 kb 5' of DDX1 and approximately 400 kb telomeric of MYCN on chromosome 2p24. CONCLUSION: We found a similar but slightly higher frequency of amplification than previously reported. We present several DNA fragments that may belong to the CpG islands of novel genes amplified in a small subset of PNET/MB. As an example we describe for the first time the amplification of NAG in the MYCN amplicon in PNET/MB.

Effects of ethanol on working memory and attention in pigeons.

To determine whether the effects of ethanol on working memory are mediated by a secondary effect on attention, dose-response curves for ethanol were determined in eight pigeons trained under a titrating matching-to-sample (TMTS) procedure, in eight pigeons trained under a discrete-trial measure of attention, and in eight pigeons trained under a continuous-trial measure of attention. Ethanol decreased accuracy under the TMTS procedure following the three highest doses (1, 1.8, and 3 g/kg). Only the highest dose (3 mg/kg) decreased rates of responding. Attention, as measured under the discrete-trial procedure, was affected only by the two highest doses (1.8 and 3 g/kg). The 3-g/kg dose caused significant decreases in the probability of a hit and probability of a correct rejection, as well as significant increases in the probability of an error of omission and response latencies. Sensitivity to the signal decreased following 1.8 and 3 g/kg ethanol. Under the continuous-trial procedure, ethanol caused a peak in false alarms after the 1.8-g/kg dose, decreased the probability of a hit following the 1.8- and 3-g/kg doses, and increased probability of a miss at all doses. Sensitivity to the signal was not affected. A comparison of the dose-response curves for the TMTS procedure and the two measures of attention revealed that working memory (TMTS) was decreased by a lower dose than that affecting attention. This suggests that the effects of ethanol on working memory are not mediated by the subject's ability to pay attention to stimulus changes in the environment.

Somatostatin receptor gene expression in neuroblastoma.

Somatostatin receptor expression is a favorable prognostic factor in human neuroblastoma. Somatostatin receptors have been demonstrated in vitro by pharmacologic analysis of tumor tissue and in vivo by diagnostic radioreceptor scintigraphy. However, which receptor subtypes (sst(1), sst(2), sst(3), sst(4), and sst(5)) are expressed in these tumors has not yet been delineated. We used RT-PCR to analyze expression of the five somatostatin receptor genes in 32 neuroblastoma tumor specimens. All 32 tumor specimens expressed mRNA for c-abl and sst(1); sst(2) mRNA was detected in 27/32 samples and somatostatin mRNA was detected in 30/32 tumor specimens. The remaining receptor subtypes, sst(3), sst(4), and sst(5) were variably expressed. Receptor protein for sst(1) and sst(2) was visualized in tumor neuroblasts as well as in endothelial cells of tumor vessels using immunostaining with specific anti-receptor antibodies. The effect of high expression of somatostatin receptors on cell proliferation was examined in SKNSH neuroblastoma cells transfected with sst(1) and sst(2). SS(14) binding to wild-type SKNSH cells was undetectable; but the native peptide bound with high affinity to the SKNSH/sst(1) and SKNSH/sst(2) neuroblastoma cell lines. Pharmacologic analysis of binding with two long-acting analogues, CH275 and octreotide, confirmed selective expression of sst(1) and sst(2) in stably transfected SKNSH cells. Formation of neuroblastoma xenograft tumors in nude mice was significantly delayed for both SKNSH/sst(1) (P<0.001) and SKNSH/sst(2) (P<0.05) cells compared to wild-type SKNSH. We conclude that: (1) Somatostatin receptors, sst(1) and sst(2), are expressed in the majority of neuroblastomas at diagnosis; and (2) upregulation of functional sst(1) or sst(2) in neuroblastoma cell lines suppresses tumorigenicity in a xenograft model. These observations suggest that somatostatin receptors may be a useful therapeutic target in neuroblastoma.

Pharmacophore/receptor models for GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) via a comprehensive ligand-mapping approach.

Pharmacophore/receptor models for three recombinant GABA(A)/BzR subtypes (alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2) have been established via an SAR ligand-mapping approach. This study was based on the affinities of 151 BzR ligands at five distinct (alpha1-3,5,6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least nine different structural families. Examination of the included volumes of the alpha1-, alpha5-, and alpha6-containing subtypes indicated that region L(2) for the alpha5-containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other two subtypes. Moreover, region L(3) in the alpha6 subtype is either very small or nonexistent in this diazepam-insensitive subtype (see Figure 16 for details) as compared to the other subtypes. Use of the pharmacophore/receptor models for these subtypes has resulted in the design of novel BzR ligands (see 27) selective for the alpha5beta3gamma2 receptor subtype. alpha5-Selective ligand 27 when injected directly into the hippocampus did enhance memory in one paradigm (Bailey et al., unpublished observations); however, systemic administration of either 9 or 27 into animals did not provide an observable enhancement. This result is in complete agreement with the observation of Liu (1996). It has been shown (Liu, 1996; Wisden et al., 1992) that in the central nervous system of the rat (as well as monkeys and pigeons) there are several native subtypes of the GABA(A) receptor which exhibit different functions, regional distributions, and neuronal locations. Although 27 binds more potently at alpha5beta3gamma2 receptor subtypes and is clearly an inverse agonist (Liu et al., 1996; Liu, 1996), it is possible that this ligand acts as an agonist at one or more subtypes. Liu (1996) clearly showed that a number of imidazobenzodiazepines were negative modulators at one subtype and agonists at another. Therefore, selectivity for a particular subtype at this point is not sufficient to rule out some physiological effect at other GABA(A)/BzR subtypes. The inability of 27 to potentiate memory when given systemically is again in support of this hypothesis, especially since alpha1beta2gamma2 subtypes are distributed throughout the brain (Wisden et al., 1992). A drug delivered systemically is far more likely to interact with all subtypes than one delivered to a specific brain region. This observation (systemic vs intrahippocampal) provides further support for the design of more subtype-specific ligands at the BzR to accurately define their pharmacology, one key to the design of new drugs with fewer side effects.

A multicenter investigation with D-FISH BCR/ABL1 probes.

Twenty-eight laboratories evaluated a new fluorescence in situ hybridization (FISH) strategy for chronic myeloid leukemia. In a three-part study, bcr/abl1 D-FISH probes were used to study bone marrow specimens. First, laboratories familiarized themselves with the strategy by applying it to known normal and abnormal specimens. Then, collectively the laboratories studied 20 normal and 20 abnormal specimens blindly and measured workload. Finally, each laboratory and two experts studied six serial dilutions with 98-0% abnormal nuclei. Using the reported normal cutoff of < 1% abnormal nuclei, participants reported no false-negative cases and 15 false-positive cases (1-6.6% abnormal nuclei). Results provided by participants for serial dilutions approximated the expected percentages of abnormal nuclei, but those from the experts exhibited greater precision. The clinical sensitivity, precision, nomenclature, workload, recommendations for training, and quality assurance in methods using D-FISH in clinical practice are discussed.

Choosing and paying for care.

This paper presents data from before and after implementation of the 1990 NHS and Community Care Act in 1993. It shows the low proportions of the population who are covered by private health insurance and draws attention to the fact that, although some older people have considered private health insurance, few are covered. Comparing data for people aged <65 with those aged >65, the paper explores the preferred sources of help in a range of situations. The findings show that in most instances, statutory services are preferred. Data for older people aged >80 are presented comparing findings from 1990/91 and 1995, which show that use of services for which charges have been introduced appear to have fallen. Low take-up of dental and optician services are identified. The implications of the findings for social policy are considered and it is suggested: that insurance cover for long-term care should be organized at a national level; that greater attention should be given to service preferences of users and potential users; and, that the effectiveness of various health and social care services should be evaluated.

Symposium overview: the use of delayed matching-to-sample procedures in studies of short-term memory in animals and humans.

Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of working/short-term memory are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Such procedures can be useful in teasing out specific aspects of mnemonic processes including discrimination, encoding, and retention. Delayed matching-to-position, delayed matching-to-sample (DMTS), and titrating matching-to-sample procedures are highlighted. Additionally, the application of DMTS tasks in preclinical and clinical settings is presented: drug effects on memory processes can be explored preclinically in animal models; normative data have been developed in human populations where they have been used in adults to explore the relationships between mnemonic processes and specific clinical entities such as Parkinsonism, senile dementia of the Alzheimer's type, schizophrenia, and depression. Studies in children indicate that encoding and retention processes improve rapidly in the early years, plateauing prior to puberty. Noninvasive imaging techniques such as positron emission tomography (PET) indicate that activity in specific brain areas is associated with DMTS task performance and may serve to confirm roles for such structures in mnemonic processes.

Effects of drugs of abuse and scopolamine on memory in rats: delayed spatial alternation and matching to position.

Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and 30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.

Dementia and help with household tasks: a comparison of cases and non-cases.

This paper is based on data, relating to people aged 75+ living in the community, from the city of Liverpool and from a rural area of North Wales. It compares those suffering from cognitive brain disorders with those identified as being cognitively unimpaired. Levels of need, and sources of help with a range of domestic and home maintenance tasks are identified. Results show that most help for those who are cognitively impaired comes from relatives living in the same household, while help for those who are physically impaired comes primarily from spouses or relatives living in different households. Cases do not demonstrate a higher level of use of formal services than non-cases. Implications for policy and practice are discussed.

Use of electron microscopy and other special techniques in the investigation of suspected specimen contamination.

Contamination of a biopsy or surgical specimen with spurious tissue is an uncommon but potentially disastrous event. In this regard, the case of a 5-year-old boy referred for treatment of an abdominal tumor is presented. Sections made from paraffin blocks brought by the family showed both neuroblastoma and a spindle cell sarcoma, initially suggesting the possibility of divergent or mixed differentiation. However, the resemblance of the spindle cell component to well-differentiated leiomyosarcoma rather than rhabdomyosarcoma raised the suspicion that a specimen contamination had occurred. Electron microscopy was instrumental in confirming the smooth muscle nature of the sarcomatous component, leading to a fluorescence in situ hybridization study, which established that this component was incompatible with the patient's gender. This case illustrates that even when the light microscopic differential has been compromised by specimen mishandling, electron microscopy can at times provide useful information regarding specimen identity, as well as assist in sorting out the correct diagnosis.