The Incidence and Prevalence of Inflammatory Bowel Disease in the Jewish and Arab Populations of Israel.

BACKGROUND: Temporal trends in the incidence of inflammatory bowel disease (IBD) in the Arab and Jewish populations in Israel have been poorly described. OBJECTIVES: To compare the annual incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in the Arab and Jewish populations in Israel between the years 2003 and 2008. METHODS: We applied a common case identification algorithm to the Clalit Health Services database to both determine trends in age-adjusted incidence and prevalence rates for IBD in both populations during this period and estimate the burden of IBD in Israel. RESULTS: The incidence of CD in the Arab population increased from 3.1/100,000 in 2003 to 10.6/100,000 person-years in 2008, compared with a decrease in the Jewish population from 14.3/100,000 to 11.7/100,000 person-years for the same period. The incidence of UC in the Arab population increased from 4.1/100,000 in 2003 to 5.0/100,000 person-years in 2008, a low but stable rate, compared with a decrease from 16.4/100,000 to 9.5/100,000 person-years for the same time period in the Jewish population. The prevalence of both diseases increased due to the accumulation of incident cases but remained much lower among Arabs. CONCLUSIONS: Understanding the factors underlying the differences in incidence and prevalence of IBD in the Jewish and Arab populations may shed light on the genetic and environmental factors associated with these diseases.

Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn's disease (ANDANTE I and II).

OBJECTIVE: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn's disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported. DESIGN: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up. RESULTS: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn's Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis. CONCLUSIONS: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development. TRIAL REGISTRATION NUMBER: NCT01287897 and NCT01345318.

Infliximab-Related Infusion Reactions: Systematic Review.

OBJECTIVE: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. METHODS: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. RESULTS: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. CONCLUSIONS: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms.

Levels of drug and antidrug antibodies are associated with outcome of interventions after loss of response to infliximab or adalimumab.

BACKGROUND & AIMS: There is controversy about whether levels of anti-tumor necrosis factor (TNF) and antidrug antibodies (ADAs) are accurate determinants of loss of response to therapy. We analyzed the association between trough levels of anti-TNF agents or ADAs and outcomes of interventions for patients with loss of response to infliximab or adalimumab. METHODS: We performed a retrospective study of pediatric and adult patients with inflammatory bowel disease and suspected loss of response to anti-TNF agents treated at medical centers throughout Israel from October 2009 through February 2013. We examined the correlation between outcomes of different interventions and trough levels of drug or ADAs during loss of response. An additional subanalysis was performed including only patients with a definite inflammatory loss of response (clinical worsening associated with increased levels of C-reactive protein or fecal calprotectin, or detection of inflammation by endoscopy, fistula discharge, or imaging studies). RESULTS: Among 247 patients (42 with ulcerative colitis), there were 330 loss-of-response events (188 to infliximab and 142 to adalimumab). Trough levels of adalimumab greater than 4.5 mcg/mL and infliximab greater than 3.8 mcg/mL identified patients who failed to respond to an increase in drug dosage or a switch to another anti-TNF agent with 90% specificity; these were set as adequate trough levels. Adequate trough levels identified patients who responded to expectant management or out-of-class interventions with more than 75% specificity. Levels of antibodies against adalimumab >4 microgram per mL equivalent (mcg/mL-eq) or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity. Patients with high titers of ADAs had longer durations of response when anti-TNF agents were switched than when dosage was increased (P = .03; log-rank test), although dosage increases were more effective for patients with no or low titers of ADAs (P = .02). An analysis of definite inflammatory loss-of-response events (n = 244) produced similar results; patients with adequate trough levels had a longer duration of response when they switched to a different class of agent than when anti-TNF was optimized by either a dosage increase or by a switch within the anti-TNF class (P = .002; log-rank test). CONCLUSIONS: The results of this retrospective analysis suggest that trough levels of drug or ADAs may guide therapeutic decisions for more than two-thirds of inflammatory bowel disease patients with either clinically suspected or definite inflammatory loss of response to therapy.

Impaired sleep quality in Crohn's disease depends on disease activity.

BACKGROUND: Little is known concerning the relationship of disease activity and sleep disturbances in inflammatory bowel disease (IBD) and specifically in patients with Crohn's disease. AIM: This study examined the prevalence of poor sleep quality in patients with active and inactive Crohn's disease compared with healthy controls. METHODS: Participants included 108 patients with Crohn's disease attending the IBD clinic of a tertiary medical center in 2009-2010 and 36 healthy volunteers. All prospectively completed a demographic questionnaire and the Pittsburgh sleep quality index (PSQI). Patients with Crohn's disease completed the Crohn's disease activity index (CDAI) and were divided into two groups accordingly: inactive disease (CDAI ≤150) and active disease (CDAI >150). Data on disease duration, medications, complications, and treatment were collected from the medical files. RESULTS: Seventy-one patients had inactive Crohn's disease and 37 had active disease. All three groups were similar in mean age, sex distribution, and body mass index. Mean duration of Crohn's disease was 10.22 ± 8.6 years; 40 patients (37 %) had ileal disease, 16 (15 %) colonic disease, and 56 (50 %) ileo-colonic disease. Patients with active disease had a significantly higher mean ± SD global score on the PSQI (8.6 ± 2.4; indicating poorer sleep quality) than patients with inactive disease (4.6 ± 1.9) or control subjects (5.1 ± 1.7) (p < 0.0001 for both), with no significant difference between the inactive-disease and control groups. The correlation between the CDAI and PSQI scores was statistically significant (p < 0.001). CONCLUSIONS: Impaired sleep quality is associated with active Crohn's disease, but not inactive disease.

The increasing prevalence of inflammatory bowel diseases among Jewish adolescents and the sociodemographic factors associated with diagnosis.

BACKGROUND: We investigated the prevalence and sociodemographic factors associated with diagnosis of inflammatory bowel diseases (IBD) among Jewish Israeli adolescents. METHODS: A total of 953,684 Jewish Israeli adolescents (57.8% men) who underwent a general health examination at mean age 17.3 ± 0.5 years from 1998 to 2010 were included. A definite diagnosis of IBD was based on laboratory, endoscopy, and pathology reports. Covariate data included socioeconomic status (SES) as defined by the Israel Central Bureau Statistics, and origin and number of children in household. RESULTS: A total of 2021 patients with IBD were identified (0.21%) in 13 annual cohorts. The prevalence of IBD increased from 149.4 cases per 100,000 to 301.0 cases per 100,000 in the first and last cohort (Ptrend = 0.003). Independent factors associated with occurrence of IBD were SES (high: odds ratio [OR] = 1.84, 95% confidence interval [CI]: 1.60-2.1, P < 0.001; medium: OR = 1.47, 95% CI: 1.3-1.69, P < 0.001; low: reference), Western origin (OR = 1.71, 95% CI: 1.53-1.90, P < 0.001; Asia Africa: reference), and male gender (OR = 1.21, 95% CI: 1.10-1.33, P < 0.001; female: reference). Four or more children in the household were associated with reduced OR for IBD [N ≥ 4: OR = 0.70, 95% CI: 0.62-0.72, P < 0.001, N = 1-3: reference]. The OR among adolescents of Western origin-high SES was 2.95 times higher compared with adolescents of Asia-African origin with low SES. CONCLUSIONS: The prevalence of IBD doubled during the 13 years of the study period. Among this large cohort of Jewish adolescents, for each origin, higher SES was associated with increased occurrence of IBD.

The prevalence of inflammatory bowel disease in an Israeli Arab population.

AIMS: To determine the prevalence of inflammatory bowel disease among the 1.5 million Arab residents in Israel who represent 20% of the total population. METHODS: Family physicians in all Arab towns and villages were contacted to obtain information on patients with inflammatory bowel disease. Relevant clinical data were retrieved and updated to December 31, 2009. RESULTS: Information was obtained from 23/71 municipalities approached (representing 200,000 out of 1.5 million Arabs). There were 64 confirmed cases of Crohn's disease indicating a prevalence rate of 32/100,000. The rate of smoking within this cohort was lower than in the general population (1.5% vs. 40%; P<0.001). There were 44 confirmed cases of ulcerative colitis with a prevalence rate of 22/100,000. The percentage of active smokers in this cohort was 18%. Clinical remission or mild activity was observed in 75% of patients in both cohorts at the time of the survey. Fourteen patients (21%) had undergone surgery for Crohn's disease, whereas none had undergone surgery for ulcerative colitis. Twenty-eight (42%) patients with Crohn's disease and 20 (45%) with ulcerative colitis were on maintenance therapy with 5-aminosalicylic acid. Only 18% with Crohn's disease and 6.8% with ulcerative colitis had received anti-tumor necrosis factor. The most prevalent extra-intestinal manifestations were perianal disease (18%) in Crohn's disease, and arthralgia or arthritis (6.8%) in ulcerative colitis. CONCLUSIONS: We found a low prevalence rate of inflammatory bowel disease in the Israeli Arab population.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

BACKGROUND: There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. METHODS: Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. RESULTS: IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. CONCLUSIONS: Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems.

Inflammatory bowel disease: risk factors for adverse pregnancy outcome and the impact of maternal weight gain.

OBJECTIVE: To identify risk factors for adverse pregnancy outcome in women with inflammatory bowel disease (IBD) and to assess the effect of maternal pre-pregnancy weight and weight gain during pregnancy on pregnancy outcome. METHODS: A retrospective, matched control study of all gravid women with IBD treated in a single tertiary center. Data were compared with healthy controls matched to by age, parity and pre-pregnancy BMI in a 3:1 ratio. RESULTS: Overall, 300 women were enrolled, 75 women in the study group (28 with ulcerative colitis and 47 with Crohn's disease) and 225 in the control group. The rates of preterm delivery and small for gestational age were higher in the study group (13.3 vs. 5.3% p = 0.02 and 6.7 vs. 0.9%, p = 0.004). The rate of cesarean section (36 vs. 19.1%; p = 0.002), NICU admission (10.7 vs. 4.0%, p = 0.03) and low 5-Min Apgar (4.0 vs. 0.4%, p = 0.02) were increased in the study group. Disease activity within 3 months of conception [OR 8.4 (1.3-16.3)] and maternal weight gain of less than 12 kg. [OR 3.6 (1.1-12.2)] were associated with adverse pregnancy outcome. CONCLUSION: Active disease at conception and inappropriate weight gain during pregnancy are associated with increased adverse pregnancy outcome in patients with IBD.

Fecal immunochemical test and small bowel lesions detected on capsule endoscopy: results of a prospective study in patients with obscure occult gastrointestinal bleeding.

BACKGROUND: Fecal immunochemical test (FIT) is gaining popularity as a screening tool for colorectal cancer. The introduction of capsule endoscopy (CE) enables an assessment of the relationship between small bowel (SB) lesions and FIT results. AIM: To determine whether SB lesions found by CE are associated with an increased rate of positive FIT. METHODS: Consecutive patients undergoing CE for obscure occult gastrointestinal bleeding also underwent FIT. CE was performed using the PillCam SB and FIT was performed with OC-Micro (three samples, threshold 75 and 100 ng/ml). RESULTS: Fifty-one patients were included; the mean lowest hemoglobin was 9.1 ± 2.1 g/dl. Twenty-six patients (51.0%) had SB lesions identified by CE and were classified as the probable or suspected source of bleeding. At the threshold of 75 and 100 ng/ml, 12 of 26 (46.1%) and 10 of 26 (38.4%), respectively had a positive FIT. In contrast, only two of 25 (8.0%) patients without SB lesions had a positive FIT at both thresholds (P=0.002 and 0.010 respectively). The mean fecal hemoglobin in patients with SB lesions classified as probable or suspected source of bleeding versus patients with normal SB was 345.6 ± 773 and 25.0 ± 37.7 ng/ml, respectively (P=0.025). CONCLUSION: A positive FIT can be explained by significant SB lesions detected by CE. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and nonexplanatory colonoscopy should undergo further study of the SB.

Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease--case report and literature review.

Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohn's disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohn's disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohn's disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohn's disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohn's disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention.

Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease.

The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing both in clinical studies and routine practice is a key issue. Endoscopy for the colon and terminal ileum and computerized tomography or magnetic resonance imaging for the small bowel are the most direct ways to evaluate intestinal healing. However, there are many unsolved questions about the definition and the precise assessment of intestinal healing using these endoscopic and imaging techniques. Furthermore, these are relatively invasive and expensive procedures that may be inadequate for regular patients' monitoring. Therefore, biomarkers such as C-reactive protein and fecal calprotectin have been proposed as surrogate markers for intestinal healing. Nevertheless, the sensitivity and specificity of these markers for the prediction of healing may be insufficient for routine practice. New stool, blood or intestinal biomarkers are currently studied and may improve our ability to monitor intestinal healing in the future.

PET/CT enterography in Crohn disease: correlation of disease activity on CT enterography with 18F-FDG uptake.

UNLABELLED: We combined (18)F-FDG PET and CT enterography in a single examination and compared the level of (18)F-FDG uptake measured by maximal standardized uptake value (SUVmax) with the CT enterography patterns of disease activity found in patients with Crohn disease (CD). METHODS: Twenty-eight patients (mean age, 37.5 y; 11 male and 17 female) suspected of having active CD underwent PET/CT enterography. Abnormal bowel segments recognized on CT enterography were graded qualitatively for the presence of perienteric fat infiltration, the comb sign, and intramural attenuation and by quantitative measurements of mural enhancement (Hounsfield units) and thickness (mm). Also, for each patient, normal segments of the ileum and colon were noted, and CT enterography measurements of thickness and enhancement were obtained. For segments detected on CT enterography, a volume of interest was placed on the fused (18)F-FDG PET scan, and the SUVmax was obtained. RESULTS: Of the 28 patients with suspected active CD, 22 had 85 abnormal segments and 6 had no abnormal segments. SUVmax was significantly higher in the abnormal segments than in the normal segments (5.0 +/- 2.5 [95% confidence interval, 4.5-5.5] and 2.1 +/- 0.69 [95% confidence interval, 1.9-2.2], respectively; P < 0.0001). A good correlation was found between SUVmax with CT enterography measurements of mural thickness and enhancement (P < 0.00001). There was a significant difference in SUVmax between the 3 levels of disease activity found by intramural attenuation, perienteric fat infiltration, and the comb sign on CT enterography. SUVmax was significantly higher when there were intense CT enterography findings of active disease (P < 0.001). CONCLUSION: SUVmax assessment may allow an objective, reliable indication of the grade and severity of inflammation activity in abnormal segments of the bowel detected by CT enterography.

Screening colonoscopy for colorectal cancer in asymptomatic people: a meta-analysis.

OBJECTIVE: The preferred method for screening asymptomatic people for colorectal cancer (CRC) is colonoscopy, according to the new American guidelines. The aim of our study was to perform a meta-analysis of the prospective cohorts using total colonoscopy for screening this population for CRC. We looked for the diagnostic yield of the procedure as well as for its safety in a screening setting. METHODS: We included papers with more than 500 participants and only those reporting diagnostic yield of adenoma (and/or advanced adenoma) and CRC. Nested analysis were performed for secondary endpoints of complications and CRC stages when this information was available. All analyses were performed with StatDirect Statistical software, version 2.6.1 ( http://www.statsdirect.com ). RESULTS: Our search yielded ten studies of screening colonoscopy conducted in asymptomatic people that met our inclusion criteria, with a total of 68,324 participants. Colonoscopy was complete and reached the cecum in 97% of the procedures. Colorectal cancer was found in 0.78% of the participants (95% confidence interval 0.13-2.97%). Stage I or II were found in 77% of the patients with CRC. Advanced adenoma was found in 5% of the cases (95% confidence interval 4-6%). Complications were rare and described in five cohorts. Perforation developed in 0.01% of the cases (95% confidence interval 0.006-0.02%) and bleeding in 0.05% (95% confidence interval 0.02-0.09%). CONCLUSIONS: Our findings support the notion that colonoscopy is feasible and a suitable method for screening for CRC in asymptomatic people.

Assessment and validation of the new capsule endoscopy Crohn's disease activity index (CECDAI).

BACKGROUND: Capsule endoscopy is a relatively new imaging tool for the detection of small bowel pathology. The assessment of the severity of Crohn's disease by capsule endoscopy is not standardized and is limited by interobserver variations in interpreting the findings. AIM: To develop, assess and validate a new, simple capsule endoscopy Crohn's disease activity index (CECDAI) in order to grade the severity of small bowel capsule endoscopy findings. METHODS: The system involves dividing the small bowel into proximal and distal segments according to transit time and then rating each segment on the basis of three parameters: inflammation (A), extent of disease (B) and presence of strictures (C). The segmental score is calculated by multiplying the inflammation subscore by the disease-subextent score and adding the stricture subscore (A x B + C); the final score is calculated by adding the two segmental scores: CECDAI = (A1 x B1 + C1) + (A2 x B2 + C2). In the present study, four senior endoscopists (two with experience in capsule endoscopy interpretation) independently reviewed coded capsule endoscopy videos of 20 patients with Crohn's disease and rated them according to the CECDAI. Interobserver variability was analyzed by Spearman's correlation test. RESULTS: The CECDAI total scores for the 20 patients ranged from 0 to 26. The correlation for the total score assigned between every two observers was 0.867 (0.700-1.000 = strong degree association; WHO classification; P < 0.0001). The Kappa statistics for agreement among all observers for the subscores and total scores were as follows: A1, 0.31 +/- 0.05; B1, 0.25 +/- 0.05; C1 (no cases); A2, 0.51 +/- 0.05; B2, 0.57 +/- 0.05; C2, 0.27 +/- 0.07. All examiners reported that the system was simple to learn and apply. CONCLUSIONS: The CECDAI score may serve as a convenient, reliable and reproducible diagnostic and follow-up tool for use by experienced endoscopists in the evaluation of patients with Crohn's disease of the small bowel.

Preparation for colonoscopy in hospitalized patients.

Successful colonoscopy depends on good preparation of the colon before the procedure. Inadequate preparation may lead to cancelled or repeat procedures and compromise patient safety, quality of care, and cost effectiveness. The primary aim of this study was to isolate factors that affect preparation success, especially in older, more severely ill, bedridden patients. The secondary aim was to examine the possible differences in preparation quality between ambulatory and hospitalized patients and the impact of a staff educational program on the preparation of hospitalized patients for colonoscopy. The study group included 303 consecutive ambulatory patients and 104 hospitalized patients referred for colonoscopy between January and March 2002, before the department introduced an educational program on colonoscopy preparation, and 310 ambulatory patients and 105 hospitalized patients referred for colonoscopy between January and March 2003. All patients completed an ad hoc questionnaire, and the findings were compared between ambulatory and hospitalized patients and between patients treated before and after the educational program. Polyethylene glycol was used significantly more often for colonoscopy preparation in hospitalized patients than in ambulatory patients (53.1% versus 8.8%; P=.0001). The hospitalized group was characterized by more incomplete or repeated colonoscopies and poorer preparation quality. On multivariate analysis, the variables found to be independent predictors of good preparation were successful patient completion of the preparatory procedure according to instructions, colonoscopy performed for follow-up after polypectomy, and preparation with sodium phosphate. The educational intervention had no impact on the quality of preparation. In conclusion, sodium phosphate preparation and complete adherence to preparation instructions are the most important factors for successful colonoscopy preparation. Current preparatory methods for hospitalized and severely ill patients need to be revised.

"Once is Enough" in Radiometric Calibrations.

The successful development of an Optical Technology Division quality system for optical radiation measurement services has provided the opportunity to reconsider the existing calibration procedures to improve quality and reduce costs. We have instituted procedures in our calibration programs to eliminate uninformative repetitive measurements by concentrating our efforts on controlling and understanding the measurement process. The first program in our calibration services to undergo these revisions is described in this paper.

The microwave spectrum of a two-top peptide mimetic: the N-acetyl alanine methyl ester molecule.

The rotational spectrum of N-acetyl alanine methyl ester, a derivative of the biomimetic, N-acetyl alanine N'-methyl amide or alanine dipeptide, has been measured using a mini Fourier transform spectrometer between 9 and 25 GHz as part of a project undertaken to determine the conformational structures of various peptide mimetics from the torsion-rotation parameters of low-barrier methyl tops. Torsion-rotation splittings from two of the three methyl tops capping the acetyl end of the -NH-C(=O)- and the methoxy end of -C(=O)-O- groups account for most of the observed lines. In addition to the AA state, two E states have been assigned and include an AE state having a torsional barrier of 396.45(7) cm(-1) (methoxy rotor) and an EA state having a barrier of 64.96(4) cm(-1) (acetyl rotor). The observed torsional barriers and rotational constants of alanine dipeptide and its methyl ester are compared with predictions from Möller-Plesset second-order perturbation theory (MP2) and density functional theory (DFT) in an effort to explore systematic errors at the two levels of theory. After accounting for zero-point energy differences, the torsional barriers at the MP2/cc-pVTZ level are in excellent agreement with experiment for the acetyl and methoxy groups while DFT predictions range from 8% to 80% too high or low. DFT is found to consistently overestimate the overall molecular size while MP2 methods give structures that are undersized. Structural discrepancies of similar magnitude are evident in previous DFT results of crystalline peptides.

Magnetic-field-induced assemblies of cobalt nanoparticles.

Under the influence of a 0.05 T magnetic field, 15-nm diameter cobalt nanoparticles covered with surfactants in a colloidal solution assemble into highly constrained linear chains along the direction of the magnetic field. The magnetic-field-induced (MFI) chains become floppy after removal of the field, folding into three-dimensional (3D) coiled structures upon gentle agitation. The 3D structures are broken into smaller units with vigorous agitation. The nanoparticles redisperse into the solvent upon ultrasonic agitation. Optical microscopy and transmission electron microscopy (TEM) are used to characterize the morphologies of the nanoparticle assemblies at various stages of this reversible process. The hysteresis loops and zero-field cooled/field cooled (ZFC/FC) curves reveal the interparticle coupling in the assemblies. MFI assembly provides a powerful tool to manipulate magnetic nanoparticles.