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An eco-informatics tool for microbial community studies: supervised classification of Amplicon Length Heterogeneity (ALH) profiles of 16S rRNA.

Support vector machines (SVM) and K-nearest neighbors (KNN) are two computational machine learning tools that perform supervised classification. This paper presents a novel application of such supervised analytical tools for microbial community profiling and to distinguish patterning among ecosystems. Amplicon length heterogeneity (ALH) profiles from several hypervariable regions of 16S rRNA gene of eubacterial communities from Idaho agricultural soil samples and from Chesapeake Bay marsh sediments were separately analyzed. The profiles from all available hypervariable regions were concatenated to obtain a combined profile, which was then provided to the SVM and KNN classifiers. Each profile was labeled with information about the location or time of its sampling. We hypothesized that after a learning phase using feature vectors from labeled ALH profiles, both these classifiers would have the capacity to predict the labels of previously unseen samples. The resulting classifiers were able to predict the labels of the Idaho soil samples with high accuracy. The classifiers were less accurate for the classification of the Chesapeake Bay sediments suggesting greater similarity within the Bay's microbial community patterns in the sampled sites. The profiles obtained from the V1+V2 region were more informative than that obtained from any other single region. However, combining them with profiles from the V1 region (with or without the profiles from the V3 region) resulted in the most accurate classification of the samples. The addition of profiles from the V 9 region appeared to confound the classifiers. Our results show that SVM and KNN classifiers can be effectively applied to distinguish between eubacterial community patterns from different ecosystems based only on their ALH profiles.

Artificial Intelligence↗

Lipid profiles reflecting high and low risk for coronary heart disease: contribution of apolipoprotein E polymorphism and lifestyle.

To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (< 15th percentile) and high HDL-cholesterol levels (> 85th percentile) were randomly selected (n = 99) and represent subjects with a low risk lipid profile. Additionally, 95 subjects with total and HDL-cholesterol levels in the 15% around the population-median (median risk lipid profile) and 100 subjects with high TC (> 85th percentile) and low HDL-cholesterol levels (< 15th percentile) (high risk lipid profile) were selected. Compared with E3/3 subjects, the likelihood for a low risk lipid profile was considerably higher (odds ratio 14.3; 2.6-79) in female, but not in male E2-carriers (1.5; 0.3-6.7). Smoking and alcohol consumption were independently associated with a low risk lipid profile in both genders, physical inactivity only in women. The odds ratio for a high risk lipid profile was elevated in male E4-carriers (4.9; 1.1-23) only. In addition to the E4 isoform, smoking and physical inactivity, overweight was the main determinant for a high risk lipid profile (odds ratio 16.8; 3.4-82). Male overweight E4-carriers had a 50 times higher likelihood of a high risk lipid profile than E3/3 men of normal weight. In women, only overweight was independently associated with a high risk lipid profile. Our results suggest that both modifiable factors and the apolipoprotein E polymorphism contribute to a lipid profile, reflecting low, average and high risk for coronary heart disease, but effects may be gender-specific.

Adult↗

Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity.

The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.

Adult↗

Profiles of plasma progesterone before and at the onset of puberty in yak heifers.

Sixty yak heifers were closely observed to determine their ages at sexual maturity and 15 heifers were used to analyze the plasma progesterone by radioimmunoassay before and at the attainment of puberty. Yak heifers began cyclic activity at a mean (+/-S.D.) age of 33 +/- 6.7 months, but with wild variation. Fifteen heifers used to determine plasma progesterone were divided into three age groups: group I (10-14 months, n = 5), group II (20-24 months, n = 5) and group III (30-36 months, n = 5). Group I yak heifers were found to have two progesterone profiles: inactive ovary (IO) profile and low progesterone short cycle (LPSC) profile; group II had three profiles: IO profile, LPSC profile and LPNC (low progesterone normal cycle) profile; group III had three profiles: LPSC profile, LPNC profile and a normal oestrous cycle profile. It would be concluded from the present study that one or two, or even more brief rise(s) in circulating progesterone presented in yak heifers. These rises, however, were not followed by a normal luteal phase except two yak heifers that came to heat. This characteristics found in yak was obviously different with that reported in other animals.

Animals↗

Soft tissue evaluation of contemporary Caucasian and African American female facial profiles.

Previous studies suggest that esthetic Caucasian profiles exhibit fuller lips than the norm for their race, while esthetic African American profiles are similar to those of esthetic Caucasians. The present study was undertaken to compare the profiles of female Caucasian and African American models and their nonmodel counterparts. Four groups of 30 subjects were evaluated: Caucasian models [CM], Caucasian controls [CC], African American models [AM], and African American controls [AC]. The models' profiles were photographed from current fashion magazines, the photos were scanned, and 17 landmarks were digitized. Each profile was standardized for size and oriented along the N'-Sn' line on a Macintosh 6115CD computer. Control photographs were processed in a similar manner. Twenty-six variables were measured for each profile. Means, ranges, and standard deviations were computed along with unpaired, two-tailed Student's t-tests (p<0.05) to evaluate group differences. The results showed that for the AM and AC profiles, all but two of the 26 variable were similar. For the CM and CC profiles, eight variables demonstrated significant differences. Between-race comparisons demonstrated greater numbers of parameters that were significantly different: CM/AM with 18 and CM/AC, CC/AC, and CC/AM with 22 each. Most of the differences involved the lips. Vertical soft tissue proportions for the four groups did not follow a 40/20/40 ratio. Caucasian and African American models displayed significantly different profile characteristics. The African American models and controls showed similar profile features, whereas greater differences were observed between Caucasian models and controls. Based on our study, the African American profile currently presented in the mass media is not "Caucasian-like." In fact, it appears that Caucasian models display more ethnic features than African American models do Caucasian features, suggesting that previously held concepts of facial beauty may no longer apply.

Beauty↗

The temperament profiles of school-age children.

Maternal reports of child temperament were used to develop temperament profiles of school-age children. The subjects were 883 children who were between 4 and 12 years of age. The children's families varied substantially in their socioeconomic status and race/ethnicity. To develop the profiles, the dimensions derived from the School-Age Temperament Inventory were subjected to a second order principal factor analysis with varimax rotation. Pearson chi-squares were used to determine whether sociodemographic variables were proportionally represented among the profiles. Forty-two percent of the children were classified into four temperament profiles. High maintenance and cautious/slow to warm up were deemed as challenging temperaments. Industrious and social/eager to try were mirror images of those profiles and were labeled easy. Some children were both types of challenging or easy profiles. The generalizability of the profiles in relation to the sociodemographic variables of gender, age, race/ethnicity, and socioeconomic status was also examined. Challenging temperament profiles were disproportionately represented by boys, Hispanic children, and those from lower socioeconomic families. Girls were over represented in the group that included both types of easy temperaments. Social/eager to try children were more often from higher rather than lower socioeconomic status families. Clinical applications and research implications for the profiles are discussed. The profiles can be used as exemplars that parents can use to recognize their child's temperament. Further research is needed to explore whether different developmental outcomes are associated with the profiles.

Age Distribution↗

Methodological problems in pressure profile calculations for lipid bilayers.

From molecular dynamics simulations of a dipalmitoyl-phosphatidyl-choline (DPPC) lipid bilayer in the liquid crystalline phase, pressure profiles through the bilayer are calculated by different methods. These profiles allow us to address two central and unresolved problems in pressure profile calculations: The first problem is that the pressure profile is not uniquely defined since the expression for the local pressure involves an arbitrary choice of an integration contour. We have investigated two different choices leading to the Irving-Kirkwood (IK) and Harasima (H) expressions for the local pressure tensor. For these choices we find that the pressure profile is almost independent of the contour used, which indicates that the local pressure is well defined for a DPPC bilayer in the liquid crystalline phase. This may not be the case for other systems and we therefore suggest that both the IK and H profiles are calculated in order to test the uniqueness of the profile. The second problem is how to include electrostatic interactions in pressure profile calculations when the simulations are conducted without truncating the electrostatic potential, i.e., using the Ewald summation technique. Based on the H expression for the local pressure, we present a method for calculating the contribution to the lateral components of the local pressure tensor from electrostatic interactions evaluated by the Ewald summation technique. Pressure profiles calculated with an electrostatic potential truncation (cutoff) from simulations conducted with Ewald summation are shown to depend on the cutoff in a subtle manner which is attributed to the existence of long-ranged charge ordering in the system. However, the pressure profiles calculated with relatively long cutoffs are qualitatively similar to the Ewald profile for the DPPC bilayer studied here.

1,2-Dipalmitoylphosphatidylcholine↗

Evaluation of the variety of plasmid profiles in S epidermidis isolates from hospital patients and staff.

Plasmid profiling was used to determine the variability of normal flora isolates of Staphylococcus epidermidis in order to evaluate the usefulness of plasmid profiling for identifying pathogens. Fifteen hospital staff members and patients repeatedly had cultures taken from the hands and nares, and multiple isolates were examined for plasmid profiles. S epidermidis isolated from the nares of 15 neonates were also examined. The total number of isolates examined for plasmid profiles was 726. Repetition of profiles was common among the different isolates from a single sampling (one swab). The frequency of re-isolating similar profiles on different days varied from 7% to 13%. Simultaneous isolation of similar profiles from nares and hands on the same individual varied from 0% to 11%, the percentage being lower for personnel. Isolation of the same plasmid profile from different individuals occurred only twice and resulted in an assignment probability of Pa = 0.002 for isolates obtained from different individuals. Significantly more isolates from nares contained plasmids (97%) compared with isolates from hands (89%). Patients who had two or more isolates of coagulase-negative staphylococci with similar profiles were judged, clinically, to have infections in 12 of 13 cases. However, the likelihood of re-isolating an S epidermidis strain with a similar plasmid profile twice from the same person at different times was sufficiently high to prevent plasmid profiling from being used as an absolute criterion for infection.

Adult↗

A practice-profiling system for residents.

Providers are increasingly evaluated and measured as part of quality, credentialling, and reimbursement programs, an approach often used by managed care organizations. However, these evaluations are rarely used in residency training, meaning that physicians entering practice have little experience or understanding of these measures. To address this issue, in 1998 the authors successfully developed a three-part practice-profiling system for internal medicine residents at their institution that includes measures of patient satisfaction, disease-management profiles for diabetes and hypertension, and an Internet-based faculty-evaluation program. The patient-satisfaction profile utilizes a ten-question patient survey that emphasizes physician-patient communication issues. The diabetes and hypertension disease-management profiles use the resident's own patients to profile process and outcome measures for common chronic ambulatory conditions. The faculty-evaluation profile is conducted over the Internet, and allows the resident to compare faculty evaluations with those of his or her peer group. Residents receive the profiles as a packet in a scheduled session with a faculty supervisor twice each year. A total of 120 residents are profiled annually for the above measures. Residents rated the program very highly, and found the profiling program to be instructive and effective feedback. As payers and regulators increasingly use physician profiling, residents will benefit from learning the strengths and weaknesses of profiling systems early in their training.

Clinical Competence↗

Comparison of perceptions of computer-animated left- and right-facing profiles.

PURPOSE: Although scientific publications differ in displaying left- or right-facing profiles, there are few systematic studies of the possible effects of directional biases and laterality on patients' and clinicians' perceptions of treatment need, outcomes, and satisfaction. As part of a research program to quantitate the physical bases of the perceived zone of acceptability and most-pleasing facial profiles, responses to computer-animated left- and right-facing soft-tissue profile images were compared and related to eye and hand preference. MATERIALS AND METHODS: Standardized left-facing, soft-tissue profile images were captured in color and digitized. The right-facing profile was created by reversing the left profile image to display a mirror image. Using imaging and customized morphing software, retrusive and protrusive extremes were created, from which transitional frames were developed to display five features of the soft-tissue profile: upper lip, chin, bimaxillary position, lower face height, and mandible. One left- and one right-facing profile for a Class II division 1 female, and Class III male were randomly presented to 24 subjects who were asked to indicate: 1) acceptability by pressing a mouse button and releasing the button when the images were no longer acceptable; and 2) most-pleasing image by pressing the mouse button once. RESULTS: No differences were found between left- and right-profile images for zone of acceptability, midpoint of the zone of acceptability, or most pleasing; nor was there any relation to laterality measures. However, consistently higher intercorrelations among the features for the zone of acceptability were found for the left- than for the right-facing profiles for retrusive to protrusive and protrusive to retrusive excursions measured in millimeters (p < .001). The bimaxillary position accounted for most of the variance in judgments of acceptability with greater influence on the left than on the right profile. CONCLUSION: With the increasing use of computer-imaging in dental practices, the influence of psychophysical and other environmental variables on perception must be considered.

Adolescent↗

Ranking of facial profiles among Asians.

The purpose of this study was to determine the facial profile preferences in a sample of 1,189 Asian teenagers (aged 15.3 +/- 3.2 years). Five facial profile types were computer-generated by trained personnel (orthodontists and oral maxillofacial surgeons) to represent distinct facial types. Subjects were asked to rank the profiles in descending order of attractiveness. The ranking was as follows: orthognathic profile, bimaxillary retrusive profile, bimaxillary protrusive profile, mandibular retrognathic profile, and mandibular prognathic profile. The differences in rank scores between all the profile types were statistically significant (p < 0.05). Assessment of profile types among lay personnel could provide clinicians an indication into the relative attractiveness among profile types and health care workers in treatment prioritization among dysmorphic facial types.

Adolescent↗

Impact of sodium and ultrafiltration profiling on hemodialysis-related symptoms.

Dialysate sodium and ultrafiltration profiling are two methods to reduce symptoms during hemodialysis. The objective of the study was to determine the efficacy of combining these techniques to reduce symptoms in chronic hemodialysis patients. Blood volume changes were measured to determine whether any benefit of profiling could be explained through this mechanism. Patients were randomized to profiled dialysate sodium and ultrafiltration or constant dialysate sodium and ultrafiltration. The study was a two-period, two-treatment, crossover design with repeated measures. The primary outcome was hypotension and/or symptomatic events observed by the dialysis nurse. Secondary outcomes were symptom survey scores, weights, BP, and blood volume changes. Thirty-three patients were randomized. On standard treatment, 30.6% of dialysis sessions were symptomatic compared with 20.4% on profiled treatments. The odds ratio for the development of hypotension or symptomatic event on profiled treatments was 0.61 (95% confidence interval, 0.39 to 0.96) compared with standard treatment. Patients had lower symptom scores by questionnaire in both the intradialytic and the interdialytic periods during profiled treatments. Predialysis weight was greater during profiled treatments by 0.3 kg (P: = 0.008), but there were no differences in postdialysis weight, BP, or thirst. There was no difference in maximum decrease in blood volume during the two treatments (standard, -11.2%; profiled, -10.0%; P: = 0.08), but there was a significant difference in the rate of change in blood volume (standard, -2.96%/h; profiled, -1.96%/h; P: < 0.001). Decrease in blood volume, rate of change in blood volume, and predialysis weights were not associated with hypotension or symptomatic dialysis sessions. In conclusion, dialysate sodium and ultrafiltration profiling significantly reduces hemodialysis-related symptoms. Profiling reduces the slope of the blood volume curve during dialysis, but blood volume changes are not predictive of symptomatic events for an individual patient.

Aged↗

Atypical progesterone profiles and fertility in Swedish dairy cows.

The incidence of normal and atypical progesterone profiles in Swedish dairy cows was studied. Data were collected from an experimental herd over 15 yr, and included 1,049 postpartum periods from 183 Swedish Holstein and 326 Swedish Red and White dairy cows. Milk progesterone samples were taken twice weekly until initiation of cyclical ovarian activity and less frequently thereafter. Progesterone profiles were 1) normal profile: first rise in milk progesterone above the threshold value before d 56 postpartum, followed by regular cyclical ovarian activity (70.4%); 2) delayed onset of cyclical ovarian activity: low milk progesterone the first 56 d postpartum (15.6%); 3) cessation of cyclical ovarian activity: ovarian activity resumed within 56 d postpartum, but ceased for a period of 14 d or more (6.6%); and 4) prolonged luteal phase: ovarian activity resumed within 56 d postpartum, but milk progesterone remained elevated in the nonpregnant cow for a period of 20 d or more (7.3%). Swedish Holsteins had 1.5 times higher risk of atypical profile than Swedish Red and Whites. Risk of atypical profiles was 0.5 and 0.7 times lower for older cows compared with first-parity cows; 2.3 times higher for cows in tie-stalls compared with those in loose housing; 2.6 times higher for cows calving during winter compared with summer; 0.5 times lower for cows in earlier (1994-1999) calving-year groups compared with the most recent (2000-2002); 2.5 times higher for cows with planned extended calving interval compared with conventional calving interval; and 2.2 times higher for an atypical profile in previous lactation compared with a normal profile. Cows with atypical profiles had a 15-d increase in interval from calving to first artificial insemination and an 18-d increase in interval from calving to conception. Progesterone samples taken within the first 60 d postpartum were used to calculate the percentage of samples above the threshold value of luteal activity. This measure had a significantly different mean in profiles and can be used to separate delayed onset of cyclical ovarian activity profiles and prolonged luteal phase profiles from normal. Thereby, it may be a more effective tool than measurements based only on the onset of ovarian cyclical activity in genetic evaluation of early postpartum fertility in dairy cows.

Aging↗

Sodium balance-neutral sodium profiling does not improve dialysis tolerance.

BACKGROUND: Modern haemodialysis monitors offer computerised ultrafiltration and sodium concentration profiles which promise better dialysis tolerance. This presumption was tested in chronic haemodialysis patients. METHODS: Using Fresenius MC 4008S monitors a group of nine patients were dialysed with a given ultrafiltration profile comparing sessions with decreasing sodium concentration (145 to 133 mmol/L) to sessions with constant sodium concentration (138 mmol/L) in random order. The built-in blood volume monitor recorded changes in haematocrit and blood volume during each dialysis. The analyses included dialytic weight loss, interdialytic weight gain and adverse symptoms (hypotensive episodes and muscle cramps). RESULTS: 321 dialysis sessions, 160 with and 161 without sodium profile, were available for analysis. No significant differences could be detected regarding changes in haematocrit, blood volume and weight in relation to sodium profiling. No significant difference in the incidence of hypotension or muscle cramping was observed with 55 symptomatic dialyses of 160 with sodium profile, compared to 52 symptomatic dialyses of 161 without sodium profile. Interdialytic weight gain and consequent weight loss during dialysis was higher in symptomatic dialyses both with sodium profile or without sodium profile. The same was true of increase in haematocrit and decrease in blood volume, which were greater for symptomatic versus symptom-free dialyses irrespective of sodium profiling. CONCLUSIONS: Sodium balance-neutral sodium profiling failed to improve dialysis tolerance in a group of stable chronic haemodialysis patients. This may be explained by the fact that vascular refilling as deduced from changes in haematocrit was uninfluenced by sodium profiling.

Aged↗

Perinatal outcome with the modified biophysical profile.

OBJECTIVE: Our purpose was to evaluate perinatal outcomes in high-risk pregnancies monitored with a modified biophysical profile. STUDY DESIGN: All non-insulin-dependent patients referred for antepartum fetal surveillance received a modified biophysical profile biweekly. A modified biophysical profile is a combination of a nonstress test and an amniotic fluid index. Patients with a singleton gestation and intact membranes were entered into a protocol of randomized backup testing for an abnormal modified biophysical profile. Those patients having a nonreactive fetal heart rate, significant variable decelerations, late decelerations, or an amniotic fluid index < or = 5.0 cm received either a contraction stress test or a biophysical profile immediately. Once randomized, a patient received the same backup test, when indicated, with subsequent testing. RESULTS: A total of 2774 patients had 17,429 tests with an uncorrected perinatal mortality rate of 2.9 per 1000. The overall incidence of an adverse perinatal outcome (i.e., perinatal death or nursery death before infant hospital discharge, cesarean delivery for fetal distress within the first 2 hours of labor, 5-minute Apgar score < 7, neonatal seizures or grade III or IV central nervous system hemorrhage) was 7.0%. When compared with patients having persistently normal modified biophysical profile, patients requiring a backup test had a significantly greater incidence of adverse perinatal outcome (9.3% vs 4.9%, p < 0.001, odds ratio 2.0, 95% confidence interval 1.5 to 2.7) and small-for-gestational-age infants (5.2% vs 2.4%, p < 0.001, odds ratio 2.2, 95% confidence interval 1.5 to 3.5). No differences in outcomes between patients randomized to a contraction stress test versus a biophysical profile could be identified either overall or in limiting the analysis to outcome after a negative last test. However, patients having contraction stress test as a backup test had a significantly higher rate of intervention for an abnormal test result than did those having a biophysical profile backup test (23.7% vs 16.6%, p < 0.002, odds ratio 1.6, 95% confidence interval 1.2 to 2.1). CONCLUSION: The modified biophysical profile is an excellent means of fetal surveillance and identifies a group of patients at increased risk for adverse perinatal outcome and small-for-gestational-age infants. There does not appear to be a significant benefit with the contraction stress test compared with the biophysical profile as a backup test. Further, the contraction stress test is associated with a higher rate of intervention for an abnormal test than is the biophysical profile.

Adult↗

A comparative study of the work involved in measuring profiles using an ion chamber, a linear diode array and film.

In this work a method of using Kodak X-Omat V film to measure beam profiles for dynamically wedged fields is presented. Also, the profiles determined by film measurement are compared with those measured with an ion chamber (0.12 cm3 Scanditronix RFA 300 RK) and an array of silicon diodes (11 channel Scanditronix linear diode array). The beam investigated is a 6 MV photon beam from a Varian 2100 C linear accelerator. The geometric method of positioning film and determining the central axis (CAX) position of the beam yielded results which agreed to within 1 mm with the software determined position of the CAX. The profiles measured by film agreed well with the ion chamber measured profiles in terms of overall field size, position, penumbral width, height and position of maximum and profile shape between the 20% dose levels. Film profiles deviated most from ion chamber profiles in the post-penumbra regions. Linear diode array (LDA) measured profiles matched ion chamber profiles in the post-penumbra regions, field size and general profile shape. In the region of maximum dose differences in dose of up to 4% were seen along with horizontal shifts of around 2 mm between LDA and ion chamber profiles.

Biophysical Phenomena↗

Clinical pharmacogenomics and transcriptional profiling in early phase oncology clinical trials.

Microarray-based expression profiling studies in the field of oncology have demonstrated encouraging correlations between tumor transcriptional profiles and eventual patient outcomes. These findings have fueled great interest in the application of transcriptional profiling to samples available from real-time clinical trials, and clinical pharmacogenomic objectives utilizing transcriptional profiling strategies are becoming increasingly incorporated into clinical trial study designs. Over the last few years several retrospective studies based on the profiling of archival tumor tissues suggest that transcriptional analysis of oncology samples may provide general prognosis measures, and in some cases may even predict response to specific therapies. Recently the FDA released a voluntary genomic data guidance meant to assist both regulatory agencies and pharmaceutical companies alike in evaluating the potential benefit of implementing expression profiling studies during the preclinical and clinical phases of drug development. Despite the great promise afforded by this technology, the ultimate benefit of applying transcriptional profiling in prospective clinical trials has yet to be realized because a number of practical impediments to this process exist. The multi-fold purpose of the current review is to highlight the increasing evidence from studies that have identified transcriptional signatures in archived tumors prognostic of patient outcome, to describe some of the drivers for the implementation of transcriptional profiling strategies in real-time drug development, to discuss the use of transcriptional profiling in the context of increasingly complex translational medicine strategies, and to highlight the practical issues and potential approaches involved in the successful application of clinical pharmacogenomic objectives during real-time clinical trials. Strategic implementation of transcriptional profiling in early oncology clinical trials can provide an opportunity to identify predictive markers of clinical response and eventually provide a substantial step forward towards the era of personalized medicine.

Antineoplastic Agents↗

Use of latent profile analysis to identify eating disorder phenotypes in an adult Australian twin cohort.

CONTEXT: The relationships among the different eating disorders that exist in the community are poorly understood, especially for residual disorders in which bingeing or purging occurs in the absence of other behaviors. OBJECTIVE: To examine a community sample for the number of mutually exclusive weight and eating profiles. DESIGN: Data regarding lifetime eating disorder symptoms and weight range were submitted to a latent profile analysis. Profiles were compared regarding personality, current eating and weight, retrospectively reported life events, and lifetime depressive psychopathology. SETTING: Longitudinal study among female twins from the Australian Twin Registry in whom eating was assessed by a telephone interview. PARTICIPANTS: A community sample of 1002 twins (individuals) who had participated in earlier waves of data collection. MAIN OUTCOME MEASURES: Number and clinical character of latent profiles. RESULTS: The best fit was a 5-profile solution with women who were (1) of normal weight with few lifetime eating disorders (4.3%), (2) overweight (10.6% had a lifetime eating disorder), (3) underweight and generally had no eating disorders except for 5.3% who had restricting anorexia nervosa, (4) of low to normal weight (89.0% had a lifetime eating disorder), and (5) obese (37.0% had a lifetime eating disorder). Each profile contained more than 1 type of lifetime eating disorder except for the third profile. Women in the first and third profiles had the best functioning, with women in the fourth and fifth profiles having similarly poorer functioning. The women in the fourth group had a symptom profile distinctive from the other 4 groups in terms of severity; they were also more likely to have had lifetime major depression and suicidality. CONCLUSION: Lifetime weight ranges and the severity of eating disorder symptoms affected clustering more than the type of eating disorder symptom.

Adult↗