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Background: The emergence of minimally invasive techniques in foot and ankle surgery has aimed to reduce iatrogenic tissue insult by utilising the smallest possible incision area to achieve maximum correction of pathological structures. The objective of this study was to assess whether adequate hallux valgus correction can be achieved via the minimally invasive chevron akin (MICA) procedure. Methods: A retrospective analysis was conducted for a single-surgeon case series of 169 MICA procedures between June 2018 and June 2021 in Australia. Radiographic parameters were evaluated independently by two researchers using 1-2 intermetatarsal angle (1-2 IMA) and hallux valgus angle (HVA) as key measures of procedural outcome. Results: 95% of participant-operations resulted in normal 1-2 IMA and HVA being obtained post-operatively in a cohort that largely consisted of moderate hallux valgus deformities; 1-2 IMA Reduction: 6.38° ± 3.24 (95% CI 5.89 to 6.87) and HVA Reduction: 20.17° ± 7.69 (95% CI 19.01 to 21.33). Conclusion: The results of this study help to further strengthen support for the use of minimally invasive bunion surgery as a primary treatment approach in mild to moderate hallux valgus.

Physician burnout affects more than half of U.S. physicians, is multifactorial in origin, and should be addressed at organizational, group, and individual levels. By examining the career of one private practice interventional radiologist, insight into lessons learned and strategies for promotion of a fulfilling career might apply to others. Priorities may vary depending on stage of career, but some common themes of meaning and purpose that most interventional radiology (IR) physicians embrace throughout their careers emerge. Recognizing and cultivating these might provide keys to mitigating professional burnout and promoting a fulfilling IR career.

The purpose of this study was to determine if 8 weeks of exercise affects motor control in people with chronic low back pain (CLBP), measured by anticipatory (APAs) and compensatory postural adjustments (CPAs). APAs and CPAs were measured prior to and following 8 weeks in two groups of people with CLBP: an exercise group (n=12) who attended three exercise sessions per week for 8 weeks; and a non-exercise control group (n=12) who were advised to continue their usual activities for the duration of the study. APAs and CPAs were recorded during unilateral arm flexion, bilaterally from rectus abdominis (RA), transverse abdominis/internal oblique (TA/IO), and erector spinae (ES) via surface electromyography. Analysis of muscle onsets and APA amplitudes suggests APAs did not change for either group. Ipsi-lateral TA/IO CPAs increased for the exercise group and ipsi-lateral TA/IO CPAs decreased for the control group. Only exercise promoted a pattern of TA/IO activity during CPAs similar to healthy individuals, suggesting improved control of rotational torques. These results show motor control improvement following exercise in people with CLBP, highlighted by improved side specific control of TA/IO.

We examined the effects of a 12-week program of Nordic hamstring exercises (NHE), administered before or after football training, upon eccentric hamstring strength, muscle activity, and architectural adaptations. Amateur soccer players were randomized into three groups. The control group (CON; n=11) undertook core stability exercises, whereas a periodized NHE program was delivered either before (NHEBEF ; n=10) or after (NHEAFT ; n=14) biweekly training sessions. Outcome measures included peak torque and concomitant normalized peak surface electromyography signals (sEMG) of the biceps femoris (BF) and medial hamstring (MH) muscles during knee flexor maximal eccentric contractions, performed at 30°·s-1 . Ultrasonography was used to determine BF muscle thickness, muscle fiber pennation angle, and fascicle length. Performing the NHE derived likely moderate peak torque increases in both NHEBEF (+11.9%; 90% confidence interval: 3.6%-20.9%) and NHEAFT (+11.6%; 2.6%-21.5%) vs CON. Maximum sEMG increases were moderately greater in the BF of both NHE training groups vs CON. There were likely moderate increases in BF muscle thickness (+0.17 cm; 0.05-0.29 cm) and likely small pennation angle increases (+1.03°; -0.08° to 2.14°) in NHEAFT vs CON and NHEBEF . BF fascicle length increases were likely greater in NHEBEF (+1.58 cm; 0.48-2.68 cm; small effect) vs CON and NHEAFT . A 12-week eccentric hamstring strengthening program increased strength and sEMG to a similar magnitude irrespective of its scheduling relative to the football training session. However, architectural adaptations to support the strength gains differed according to the timing of the injury prevention program.

Low health literacy disproportionately affects racial and ethnic minority communities and lower-income socioeconomic groups. To address this critical determinant of health inequity, two nonprofit organizations, Repairers of the Breach, a day shelter for individuals experiencing homelessness, and Bread of Healing a neighborhood-based clinic serving individuals with low incomes, partnered with researchers at Marquette University to implement and evaluate an evidence-supported health literacy program. The partnership delivered the curriculum in seven one-hour sessions over seven weeks. The program attendees were predominantly African American men and women from 19–73 years old. Most participants had formal education ranging from elementary school to some college. Forty individuals attended at least one class and 14 attendees completed 4 or more classes. Program completers demonstrated gains in confidence and topic knowledge. Most interviewees reported a personal/family need for the program, acceptability of the group format, and the ability to learn the skills they needed for self-care. The project used a successful collaboration between community-based organizations serving vulnerable populations and an urban academic institution to demonstrate the necessity, feasibility, acceptability, and effectiveness of formal health literacy education in adults with low incomes or who are experiencing homelessness. Urban and metropolitan serving institutions can work in partnership with community to address low health literacy in high need populations.

The optimal scheduling of Nordic Hamstring exercises (NHEs) relative to football training sessions is unknown. We examined the acute neuromuscular and performance responses to NHE undertaken either before (BT) or after (AT) simulated football training. Twelve amateur players performed six sets of five repetitions of the NHE either before or after 60 min of standardised football-specific exercise (SAFT60). Surface electromyography signals (EMG) of the hamstring muscles were recorded during both the NHE, and maximum eccentric actions of the knee flexors (0.52 rad · s-1) performed before and after the NHE programme, and at 15 min intervals during SAFT60. Ten-metre sprint times were recorded on three occasions during each 15 min SAFT60 segment. Greater eccentric hamstring fatigue following the NHE programme was observed in BT versus AT (19.8 %; very likely small effect), which was particularly apparent in the latter range of knee flexion (0-15°; 39.6%; likely moderate effect), and synonymous with hamstring EMG declines (likely small-likely moderate effects). Performing NHE BT attenuated sprint performance declines (2.0-3.2%; likely small effects), but decreased eccentric hamstring peak torque (-14.1 to -18.9%; likely small effects) during football-specific exercise. Performing NHE prior to football training reduces eccentric hamstring strength and may exacerbate hamstring injury risk.

PURPOSE To evaluate the clinical effectiveness of ultrasound-assisted thrombolysis (USAT) in resolution of right ventricular dysfunction (RVD), preservation of cardiopulmonary function, and quality of life (QoL) in patients with acute submassive pulmonary embolism (PE). MATERIALS AND METHODS A single-center prospective study of patients presenting with acute PE and signs of RVD, as determined by right ventricle-to-left ventricle diameter ratio (RV:LV) > 0.9 on computed tomographic angiography of the thorax, was performed. Patients underwent USAT with recombinant tissue plasminogen activator. Primary endpoints measured were RV:LV by echocardiogram at baseline presentation and at 72 hours and 90 days after treatment. Secondary endpoints were QoL scores assessed by SF-36 Health Surveys at baseline and at 90 days, cardiopulmonary exercise test (CPET) parameters at 90 days, and procedural outcomes, including response of pulmonary artery pressure (PAP) and procedural complications. RESULTS Twenty-five patients were treated between June 17, 2013, and September 15, 2014, with mean reduction of RV:LV by echocardiogram from 1.38 ± 0.28 at presentation to 0.92 ± 0.14 (P < .0001) at 72 hours and 0.84 ± 0.25 (P < .0001) at 90 days. SF-36 Health Survey scores demonstrated no long-term self-perceived adverse physical or mental effects as a result of PE. CPET parameters, including VO2max, weight-adjusted VO2, VE/VCO2, and VD/VT demonstrated no pulmonary vascular impairment at 90 days. PAP significantly improved after USAT, with mean initial systolic pressure of 50.46 ± 13.98 mmHg reduced to 39.64 ± 8.66 mmHg (P = .0001). There were no deaths, recurrent venous thromboembolism, hemodynamic decompensation, or hemorrhage. CONCLUSIONS USAT resulted in significant reduction of RV:LV at 72 hours, which was preserved at 90 days. QoL and objective measures of cardiopulmonary function are preserved at 90 days in this population. Further studies with long-term follow-up are needed to determine the potential value of USAT for the prevention of post-PE syndrome in patients with submassive PE.

The premise of eliciting the greatest acute fatigue is accepted and used for designing programs that include excessive, potentially dangerous volumes of high-intensity resistance exercise. There is no evidence examining acute fatigue and neuromuscular responses throughout multiple sets of moderate-to-high intensity resistance exercise. Fifteen resistance-trained male subjects performed a single exercise session using 8 sets of Bulgarian split squats performed at 75% maximal force output. Maximal force output (N) was measured after every set of repetitions. Electromyographic (EMG) activity of vastus lateralis was monitored during all force trials and exercise repetitions. Repetitions per set decreased from the first to the third set (p < 0.001). Maximal force output decreased from preexercise to set 4 (p < 0.001). Electromyographic amplitudes during exercise did not change. Secondary subgroup analysis was performed based on the presence, or not, of a fatigue plateau (

Controversy exists regarding the structural and functional causes of hallux limitus, including metatarsus primus elevatus, a long first metatarsal, first-ray hypermobility, the shape of the first metatarsal head, and the presence of hallux interphalangeus. Some articles have reported on the radiographic evaluation of these measurements in feet affected by hallux limitus, but no study has directly compared the affected and unaffected feet in patients with unilateral hallux limitus. This case-control pilot study aimed to establish whether any such differences exist.Dorsoplantar and lateral weightbearing radiographs of both feet in 30 patients with unilateral hallux limitus were assessed for grade of disease, lateral intermetatarsal angle, metatarsal protrusion distance, plantar gapping at the first metatarsocuneiform joint, metatarsal head shape, and hallux abductus interphalangeus angle. Data analysis was performed using a statistical software program.Mean radiographic measurements for affected and unaffected feet demonstrated that metatarsus primus elevatus, a short first metatarsal, first-ray hypermobility, a flat metatarsal head shape, and hallux interphalangeus were prevalent in both feet. There was no statistically significant difference between feet for any of the radiographic parameters measured (Mann-Whitney U tests, independent-samples t tests, and Pearson χ(2) tests: P.05).No significant differences exist in the presence of the structural risk factors examined between affected and unaffected feet in patients with unilateral hallux limitus. The influence of other intrinsic factors, including footedness and family history, should be investigated further.

Sparse linear algebra is a cornerstone of modern computational science. These algorithms ignore the zero-valued entries found in many domains in order to work on much larger problems at much faster rates than dense algorithms. Nonetheless, optimizing these algorithms is not straightforward. Highly optimized algorithms for multiplying a sparse matrix by a dense vector, for instance, are the subject of a vast corpus of research and can be hundreds of times longer than naive implementations. Optimized sparse linear algebra libraries are thus needed so that users can build applications without enormous effort.Hardware vendors release proprietary libraries that are highly optimized for their devices, but they limit interoperability and promote vendor lock-in. Open libraries often work across multiple devices and can quickly take advantage of new innovations, but they may not reach peak performance. The goal of this work is to provide a sparse linear algebra library that offers both of these advantages.We thus describe clSPARSE, a permissively licensed open-source sparse linear algebra library that offers state-of-the-art optimized algorithms implemented in OpenCL™. We test clSPARSE on GPUs from AMD and Nvidia and show performance benefits over both the proprietary cuSPARSE library and the open-source ViennaCL library.

Oncologists recommend chemotherapy to postmenopausal women with adverse prognostic factors, but predictors of the benefit of chemotherapy are mainly based on mortality from symptomatic cancer trials. From 1990 to 1998, 1475 breast cancers (875 screen detected cancers [SDBCs]: 600 symptomatic) were treated in women aged 50–65 years and prognostic factors compared with cancer mortality. Median follow-up was 110 months. The Nottingham Prognostic Index (NPI) was calculated for 6737 breast cancers which were part of the Association of Breast Surgery (ABS) 2001/2002 Audit of SDBCs to validate survival figures. Ten year survival was 92.1% for SDBC and 77.6% for symptomatic cancers. Adjusting for baseline factors, SDBCs had a reduced mortality (RR = 0.42 (0.31–0.57), independent of grade, node status and tumour size. Oestrogen receptor (ER) positive SDBC had a lower annual mortality rate (0.6%) compared with symptomatic (4.3%: P

Background— The optimal degree of heparin anticoagulation for peripheral vascular interventions (PVIs) has not been defined. We sought to correlate total heparin dose and peak procedural activated clotting time (ACT) with postprocedural outcomes in patients undergoing PVI. Methods and Results— We studied 4743 patients who received heparin during PVIs in a regional, multicenter registry. From those, 1246 had recorded peak procedural ACT with the same point-of-care device. Periprocedural and in-hospital outcomes were compared between patients who received a total heparin dose P =0.004) and a higher transfusion rate compared with those with heparin dose P =0.002). In multivariate analysis, independent predictors of bleeding requiring transfusion were total heparin dose ≥60 U/kg, ACT ≥250 seconds, female sex, age ≥70 years, prior anemia, prior heart failure, low creatinine clearance, hybrid vascular surgery, rest pain, and below-knee intervention. In propensity-matched, risk-adjusted models and after hierarchical modeling, total heparin dose ≥60 U/kg and ACT ≥250 seconds remained strong predictors of post-PVI drop in hemoglobin ≥3 g/dL or transfusion. Conclusions— During PVI, higher total heparin dose (≥60 U/kg) and peak ACT ≥250 seconds were predictors of postprocedural transfusion. The high technical and procedural success in all groups suggests that use of weight-based heparin dosing with a target ACT

Background: Meta-analysis of symptomatic breast cancer trials advises chemotherapy to women less than 70 years of age at high risk of death (i.e benefit of >1% survival benefit from treatment) but UK screen detected breast cancers (SDBC) in women aged 50 to 65 years have a 97.2% relative survival compared to 77.6% for symptomatic cancers in the ABS at BASO audit. Methods: To determine which women benefit from chemotherapy, we have analysed 1,607 symptomatic and SDBC in one unit. Results: SDBC had a significantly lower risk of relapse with the five year breast cancer mortality for ER positive breast cancers being low in the Excellent, Good and Moderate Prognostic Group 1 but being significantly higher in the Good Prognostic Group and Moderate Prognostic Group 1 diagnosed symptomatically. Symptomatic cancers in the Good Prognostic Group (GPG) and Moderate Prognostic Group 1 (MPG1) had a hazard ratio of 5.34 (1.61-17.75) and 14.46 (10.4-106.0) respectively for cancer death compared to SDBC. NPI Index Score and Mortality in SDBC and Symptomatic Cancers treated in Manchester 1990-98 - ER ER positive cancers detected by screening (but not ER negative) had a 0.6% mortality annually whereas the symptomatic cancers had a 10% annual mortality in the first five years. The UK National ABS/BASO Audit was used to confirm the findings (Table 2). Data over the last ten years of follow-up from the ABS at BASO audit indicates significant survival improvements in the Moderate Prognostic Group 2 (MPG2) and the Poor Prognostic Group (PPG) for SDBC. NHSBSP and ABS at BASO Breast Screening National Audit Data for Invasive SDBCs diagnosed between 1990 and 2002 Discussion: Thus, ER positive SDBCs represent a group which have a low risk of relapse and do not require chemotherapy. The improvements in survival of SDBC relate to better treatment of ER negative and HER2 positive breast cancers and have occurred predominantly in the MPG2 and PPG. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-07.

Background: UK screen detected breast cancers (SDBC) (aged 50-65 years) have an overall 97.2% 5 year relative survival compared to 77.6% for symptomatic cancers. Epithelial proliferation has been used to determine therapy in the St. Gallen guidelines (Ki67 ≥30% indicates the need for chemotherapy). Methods: To determine the value of Ki67 in post-menopausal breast cancer in women aged 50-65 years, we have studied Ki67 in 1270 women aged 50-65 years (mean 57 years) with either symptomatic cancers (n=412) or SDBC (n=858) with a 10 year follow up. Results: Ki67 predicted relapse and death in both symptomatic and SDBC. Mode of detection, size, grade, node status and oestrogen receptor (ER) were independently predictive of breast cancer mortality and Ki67 was not an independent variable. In small size ≤15mm ER positive SDBC (n=248) or symptomatic cancers (n=146), Ki67 was not prognostic (p=0.13 and 0.59 respectively). Twelve per cent of symptomatic and 2% of SDBC had died within 5 years. Mean Ki67 in SDBC was 21.4 (SD 10.3) and 34.2 (SD 16.2) in symptomatic cancers (p=≤0.001). ER positive cancers had lower Ki67 levels (p=0.002). For each 10 unit increase in Ki67, increases in distant relapse occurred (RR 1.43:95%CI;1.32-1.55). Ten Year Survival According to Ki67 and Mode of Presentation Discussion: Epithelial proliferation is prognostic in breast cancer but its value is predominantly in large size (≥15mm) symptomatic tumours and Ki67 alone cannot be used to determine therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-31.

Background: Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. Methods: This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q ≤8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups. Results: In all, 104 CD patients met criteria for 3-year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD-related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to $11,464 in spite of both cohorts being on SM therapy. Conclusions: Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen. (Inflamm Bowel Dis 2010)

Background: There are relatively few articles addressing long-term follow-up in women with breast cancer at very young ages. Methods: We have updated and extended our population-based analysis of breast cancer diagnosed at the age ⩽30 years in North-west England to include an extra 15 patients with mutation testing in BRCA1, BRCA2 and TP53, with 115 of 288 consecutive cases being tested. Kaplan–Meier curves were generated to assess overall survival, contralateral breast cancer and other second primaries. Results: Survival analysis of all 288 patients showed poor overall survival, although this improved from a 15-year survival of only 46% in those diagnosed between 1980 and 1989 to 58% in those diagnosed between 1990 and 1997 (P=0.05). Contralateral breast cancer rates were at a steady rate of 0.6 per 1000, although the rates in mutation carriers were ∼2 per 1000. Altogether, 16 BRCA1, 9 BRCA2 and 6 TP53 mutations have now been found among the 115 cases on whom DNA analysis has been performed. BRCAPRO accurately predicted the number of carriers for BRCA1 and BRCA2 and was sensitive and specific at the 10 and 20% threshold, respectively. However, BRCAPRO did not seem to give any weight to DCIS, which accounted for two BRCA1 carriers and three TP53 carriers and overpredicted mutations at the high end of the spectrum, with only 6 of 11 (54%) with a >90% probability having identifiable BRCA1/2 mutations. Interpretation: Rates of new primaries are predicted to some extent by mutation status. BRCAPRO is useful at determining those patients aged ⩽30 years to be tested.

Background: Patients who require hospitalization for the management of ulcerative colitis (UC) may represent a subset with severe disease. These patients may be more likely to require future colectomy. There are limited data examining whether medical hospitalization is predictive of subsequent colectomy. Methods: This was a retrospective case–control study utilizing the inflammatory bowel disease center database at our academic referral center. Cases comprised UC patients who underwent colectomy for disease refractory to medical management. The control population was comprised of all patients with UC who had not undergone colectomy. Multivariate logistic regression was used to identify independent predictors of requiring colectomy. Results: There were a total of 246 UC patients included in our study, with 103 being hospitalized sometime in their disease course (41.9%). A total of 27 patients underwent colectomy (11%). Colectomy patients were significantly more likely to have been on infliximab therapy (51.8% versus 22.4%, P = 0.001) but no more likely to have been on immunomodulator therapy (74.1% versus 59.4%, P = 0.14). Patients who required medical hospitalization for UC were more likely to require future colectomy (20.4% versus 4.2%, P < 0.001) than those who had not required hospitalization. On multivariate analysis, requiring medical hospitalization for management of UC (odds ratio [OR] 5.37, 95% confidence interval [CI] 2.00–14.46) and ever requiring infliximab therapy (OR 3.12, 95% CI 1.21–8.07) were independent predictors of colectomy. Conclusions: Requiring medical hospitalization for the management of disease activity in UC is an independent predictor of the need for colectomy. Future studies will determine whether aggressive medical management may modify the need for colectomy in this cohort. (Inflamm Bowel Dis 2008)

Background: There is no standard approach for the medical management of Crohn's disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort® EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH- and time-dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohn's disease. There is no available data on the safety of using oral budesonide in pregnant patients. Methods: We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies. Results: The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1-8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities. Conclusion: Budesonide may be a safe option for treatment of CD during pregnancy. (Inflamm Bowel Dis 2008)

Transarterial catheter embolization (TAE) is integral in the management of lower gastrointestinal bleeding (BLGIT). The efficacy of superselective embolization has reduced the need for emergent surgical resection as a treatment modality. Objective To determine the outcomes of TAE in the management of BLGIT in terms of efficacy rates, recurrent bleeding rates and long term results without the need for surgical intervention. Method Patients who underwent TAE for BLGIT between September 2000 and May 2006 were analysed. Data were extracted from the records for analysis. Results Sixty-eight patients with a mean age of 76 years and equal gender distribution were analysed. Sixty-nine per cent presented with haematochezia, 40% with malena. Sixty-three patients had a prior RBC scan performed, all of which were positive. Colonoscopy was attempted in 18 patients of which four managed to localize the bleeding site. Embolization was performed in these patients using mainly polyvinyl alcohol particles and/or microcoils. The morbidity rate was 21%, comprising mainly fever and nonspecific abdominal pain with only four ischaemic complications and one report of colonic infarction. Early recurrent bleeding occurred in six patients. Three were treated with repeat embolization and two required surgery. There were no mortalities. After a mean follow-up of 12 months, 12 (17.6%) patients developed further episodes of BLGIT, necessitating further intervention. Conclusion Transarterial catheter embolization is effective and safe in the acute management of BLGIT and reduces the need for further definitive surgery in a majority of patients.

Purpose To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor–positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy. Patients and Methods Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization. Results Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile. Conclusion Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.

Survey-based epidemiologic studies suggest that restless legs syndrome (RLS) affects approximately 10% of the general population and can cause significantly reduced quality of life due to sleep disturbance. This condition is more prevalent in certain disease states, such as iron deficiency anemia, neuropathy, and renal insufficiency. No such prevalence data exists for RLS in liver disease. The aim of the present project was to assess the self-reported prevalence of RLS using an RLS symptom specific questionnaire in patients presenting to a tertiary hepatology clinic with chronic liver disease (CLD). This was a convenience cohort study of established chronic liver disease patients being seen at a tertiary referral center. A one-page survey querying RLS symptoms was administered in hepatology clinic to patients with chronic liver disease. Restless legs syndrome (RLS) symptoms as agreed upon by the International RLS Study Group were incorporated as 5 key questions. Of 141 completed surveys, 88 were positive yielding a questionnaire based prevalence of RLS of 62% in this select population. RLS risk factors were further assessed through chart review and self-report and using a logistical regression analysis. Comparison between those reporting RLS symptoms and those who did not revealed only self-reported neuropathy to be significantly higher in those with RLS. RLS associated with risk factors accounted much of the total prevalence. Of those with RLS symptoms, 23 surveyed were without known RLS risk factors. This yields a convenience sample prevalence of unexplained RLS symptoms of 16.3% (CI: 10.6-23.5) in this population. There did not appear to be a correlation between the severity of liver dysfunction including the presence of cirrhosis or the etiology and the prevalence of RLS symptoms. Quality of Life (QoL) surveys specific to RLS completed suggest RLS symptoms result in significantly diminished QoL, with an average QoL score of 68 on a 0-100 scale.This study is the first investigation of RLS prevalence in liver dysfunction. This select population of medically complex patients who all have some degree of liver dysfunction appear to have a surprisingly high prevalence of RLS symptoms. While much of this prevalence may be the result of known secondary causes further investigation is warranted to explore the relationship between RLS and liver dysfunction.

OBJECTIVE: Crohn's disease (CD) frequently presents during early adulthood, a peak time of work productivity. There are limited data from the United States on work disability from CD. We performed this study to identify clinical factors associated with permanent work disability in a CD tertiary referral cohort. METHODS: Cases were identified as patients who received permanent work disability compensation from the social security administration (SSA) related to CD. Four control patients who were not receiving work disability were selected for each case. Multivariate logistic regression was performed to identify characteristics that were independently associated with work disability. RESULTS: A total of 737 patients with CD were seen in our center, and 185 CD patients were included in our study (37 disability cases, 148 controls). On multivariate analysis, an SIBDQ score

Background Anticipatory (APAs) and compensatory (CPAs) postural adjustments are organised by the central nervous system (CNS) and serve to control postural perturbations. Ineffective APAs and CPAs have been hypothesised to contribute to the persistence of symptoms and disability in people with low back pain (LBP). Despite two decades of research, there is no systematic review investigating APAs and CPAs in people with LBP. Thus, the aim of the current review is to determine if APA and CPA onset or amplitude, as measured by electromyography (EMG), centre of pressure (COP), and kinematics, are altered in people with LBP. Methods/design A systematic review and meta-analysis will be conducted. Searches will be conducted in electronic databases for full-text articles published before January 2016 using pre-defined search strategies that utilise combinations of keywords and medical subject heading terms. Two independent reviewers will screen potentially relevant articles for inclusion, extract data, and assess risk of bias for individual studies. Any disagreements will be resolved by a third reviewer. Studies comparing APA onset and amplitude and CPA onset and amplitude measured by EMG, COP, or kinematics between people with LBP and healthy individuals will be included if all aspects of the eligibility criteria are met. Data will be synthesised if studies are homogeneous; otherwise, results will be reviewed narratively. Discussion To our knowledge, this is the first systematic review to examine APAs and CPAs, as measured by EMG, COP, and kinematics in people with LBP. The findings of this review may aid in the identification of factors that play a role in the persistence of symptoms and disability and aid in the development of interventions to treat symptoms. Systematic review registration PROSPERO CRD42016032815 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0242-4) contains supplementary material, which is available to authorized users.

The Nordic hamstring exercise (NHE) is a bodyweight movement commonly prescribed to increase eccentric hamstring strength and reduce the incidence of strain injury in sport. This study examined hamstring fatigue and muscle activation responses throughout 6 sets of 5 repetitions of the NHE. Ten amateur-level soccer players performed a single session of 6 sets of 5 repetitions of NHE. Maximal eccentric and concentric torque output (in newton meters) was measured after every set. Hamstrings electromyograms (EMG) were measured during all maximal contractions and exercise repetitions. Hamstring maximal eccentric torque was reduced throughout the range of motion after only a single set of NHE between 7.9 and 17.1% (p ≤ 0.05), with further reductions in subsequent sets. Similarly, maximal concentric torque reductions between 7.8 and 17.2% were observed throughout the range of motion after 1 set of NHE (p ≤ 0.05). During the descent phase of the NHE repetitions, hamstring muscle activity progressively increased as the number of sets performed increased. These increases were observed in the first half of the range of motion. During the ascent phase, biceps femoris muscle activity but not medial hamstrings was reduced from the start of exercise during latter sets of repetitions. These data provide unique insight into the extent of fatigue induced from a bodyweight only exercise after a single set of 5 repetitions. Strength and conditioning coaches need to be aware of the speed and extent of fatigue induced from NHE, particularly in practical settings in which this exercise is now prescribed before sport-specific training sessions (i.e., the FIFA-11 before soccer training).

Background: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. Aims/Methods: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. Results/Conclusions: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist’s practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Background: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. Aims/Methods: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using κ statistics. Results: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high—this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit—this included histological grading; (3) where consistency could be improved but only by changing the system of classification—this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved—this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. Conclusions: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC); relating expression patterns to recurrence of DCIS after surgery. Patterns of COX-2 and survivin expression were determined by intensity-graded immunohistochemistry of the primary tumours. Patients with DCIS (n=161) which had either recurred (n=47) or shown no evidence of recurrence (n=114) 5 years following primary surgery were studied. These were compared to 58 cases of IBC. Survivin was expressed in the cytoplasm of 59% of DCIS and 17% of IBC. High levels of both cytoplasmic survivin and COX-2 expression significantly correlated to DCIS recurrence. COX-2 expression was present in 72% of DCIS, and levels of expression positively correlated with cytoplasmic survivin expression in DCIS and invasive disease. The majority of DCIS that recurred expressed both proteins (69%) vs 39% nonrecurrent. Recurrence was not seen in DCIS lacking both proteins at 5 years (P=0.001). Expression of the IAP survivin is increased in DCIS and correlates closely with COX-2 expression. Increased expression of IAP, (leading to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of DCIS after surgical treatment.

Background Results of the National Surgical Adjuvant Breast Project B-24 trial indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not routinely determined in DCIS. The aim of this study was to assess the ER status in women with DCIS to determine whether any clinicopathological factors could predict positivity instead of immunohistochemical assessment. Methods The ER and progesterone receptor (PR) status of consecutive women diagnosed with DCIS during 2001 and 2002 was determined by immunohistochemistry. Results One hundred and nineteen tumours diagnosed between 2001 and 2002 were analysed; 73·0 per cent were ER positive and 61·1 per cent were PR positive. PR positivity was associated with ER positivity (P < 0·001). Increasing tumour grade correlated with a decrease in ER and PR positivity (both P = 0·002). Comedo necrosis was associated with ER negativity (P = 0·026), PR negativity (P = 0·033) and a lower percentage of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per cent; P = 0·021). Conclusion Tumour grade and comedo necrosis were not strong enough predictors to be used as surrogates for immunohistochemical assessment. ER status should be determined before commencing endocrine therapy.

Summary Background : Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia. Aim : To determine effect of vitamin E supplementation on ribavirin-associated haemolysis in chronic hepatitis C treated with standard α-interferon and ribavirin. Methods : Fifty-one naive chronic hepatitis C patients were randomized to receive either α-interferon/ribavirin therapy (control) or therapy plus vitamin E 800 IU b.d. with 24-week follow-up. Alanine aminotransferase ALT, haemoglobin and reticulocyte percentage were monitored. Symptoms and health-related quality of life were also monitored at each visit. Results : Forty-seven subjects were treated (27 vitamin E /20 controls). Thirteen withdrew because of adverse effects or non-compliance. Groups were similar in demographics, genotype and baseline lab indices. Comparison with baseline, treatment and follow-up values showed a significant haemoglobin and ALT reduction in both groups. There was no significant difference in haemoglobin and reticulocyte percentage between groups. Sustained viral response was not significantly different between vitamin E (11/18) and control (6/16) groups. Three patients required ribavirin dose-reduction in the vitamin E group compared with two controls. Health-related quality of life during and end-of-treatment was not different between groups. Conclusions : Vitamin E supplementation alone during standard α-interferon and ribavirin therapy does not appear to diminish ribavirin-associated haemolysis.

Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P

Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohn's disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. GOALS Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP.CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed.Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation.Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.

We report the case of a 44-year-old Caucasian man who was referred to our hepatology clinic because of jaundice of unclear etiology with elevated aminotransferases. The patient had been healthy and well with normal liver chemistries noted at an insurance examination six months prior to presentation. Approximately five months prior to presentation, he began using a dietary supplement, Hydroxycut, intended for weight loss, which he discontinued because of satisfactory weight loss six weeks before presentation. Four weeks later, his wife had started noticing yellowish discoloration of his eyes and skin. The patient also noted ashen stools and dark urine for approximately the same duration. He denied nausea, abdominal pain and swelling, pruritus, alteration of sleep–wake cycle, or change in mental status or in handwriting. He had a recent 30–lb intentional weight loss. He denied shortness of breath, chest pain, tremulousness, palpitations, and headaches. The patient’s aminotransferases at his primary physician’s office were: ALT 3600 IU/liter and AST 2046 IU/liter, and his total bilirubin was 3.5 mg/dl. The primary physician also obtained an abdominal ultrasound and CT scan, hepatitis A lgM and hepatitis B and C serologies, all of which were negative. Repeat liver enzymes were ALT 1046 IU/liter and AST 372 IU/liter with a total bilirubin 2.5 mg/dl, ferritin of 6882, iron 266, and transferrin 225. He was then referred to us for evaluation. Past medical history included hepatitis A ten years prior with spontaneous resolution and asthma under excellent control with inhaled medications. The family history was noncontributory.

OBJECTIVES: Endoscopic screening of cirrhotics for large esophageal varices (EV) is advocated before initiation of prophylactic therapy for variceal bleeding. Conscious sedation for conventional endoscopy is problematic in cirrhotic patients because of risk of prolonged encephalopathy. Unsedated transnasal endoscopy (T-EGD) is a new technique, which allows for unsedated examination because it is well tolerated. The aims of this study were to determine whether T-EGD is feasible for screening of cirrhotic patients for presence of EV and to compare the diagnostic yield of T-EGD with conventional endoscopy for detecting and grading of EV. METHODS: Fifteen cirrhotics with no history of variceal bleeding, known EV, severe thrombocytopenia, or recurrent epistaxis were evaluated by unsedated T-EGD using a 5.3-mm outer diameter endoscope. Immediately afterward, a different endoscopist, blinded to T-EGD findings, performed sedated conventional endoscopy in standard fashion. The presence and size of EV, gastric varices, and other findings were recorded. Patient tolerance was also evaluated. RESULTS: Both modalities detected EV in the same 10 and gastric varices in the same two patients and completely agreed on size of EV. No stigmata of recent variceal bleeding were noted. Average time for unsedated T-EGD was 5 min 6 s. All patients found both procedures acceptable overall, with no significant difference in choking, discomfort, and sore throat. One patient developed self-limited epistaxis after T-EGD. CONCLUSIONS: 1) EV are accurately detected and graded by T-EGD in cirrhotic patients. 2) T-EGD is a safe and less costly screening alternative for EV in cirrhotic patients.

Background Ductal carcinoma in situ (DCIS) expresses c-erbB-2 receptor and epidermal growth factor receptor (EGFR). The aim of this study was to determine whether blocking of c-erbB-2 receptor with a humanized monoclonal antibody, 4D5 (HerceptinTM), or of EGFR with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD1839 (IressaTM), would decrease epithelial proliferation in DCIS. Methods DCIS tissue from 18 women undergoing surgery was implanted into 16 to 20 athymic nude mice per experiment (eight xenografts per mouse). Treatment commenced 2 weeks after implantation and consisted either of twice-weekly intraperitoneal injections of 4D5 10 mg/kg or of daily gavage with ZD1839 at 100–200 mg/kg for 14 days; appropriate controls were included. Xenografts were removed on days 14, 21 and 28. Proliferation was assessed by counting 1000 epithelial cells after Ki67 immuno- staining. Results ZD1839 inhibited proliferation compared with that in controls after 14 days (P < 0·01), whereas 4D5 did not. Conclusion Proliferation in DCIS was decreased by EGFR tyrosine kinase inhibition but not by c-erbB-2 receptor blockade. ZD1839, an orally active and selective EGFR-TKI, has potential as adjuvant therapy in DCIS.

Specific terminal carbohydrate structures and mucin-associated glycans increase in expression within the human endometrial epithelium during the secretory phase of the menstrual cycle but exhibit wide intercellular variation. We postulated that variation in glycosylation between cells would produce differences in the glycocalyx and result in complex mixtures of cells bearing different combinations of glycans. MUC-1 mucin, keratan sulphate and fucosylated lactosaminoglycans were examined in epithelial gland fragment cultures with antibodies (HMFG1, 5D4) and a lectin (Dolichos biflorus agglutinin). The glycocalyx was examined by transmission and high resolution scanning electron microscopy. The data were related to patterns of expression seen in vivo. The MUC-1 mucin was expressed relatively uniformly in culture, but heterogeneity was evident in mucin sialylation within the epithelial cell population. Double labelling of gland explant cultures for combinations of fucosylated lactosaminoglycans, keratan sulphate and MUC-1 demonstrated cells expressing all combinations of these markers. Ultrastructural examination confirmed remarkable intercellular variation in the glycocalyx. Though the human endometrial epithelium is relatively morphologically homogeneous, these observations reveal complex variations of cell surface glycosylation between neighbouring cells and suggest that secretory function might vary in a similar fashion.

Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.

Mastectomy probably represents over-treatment for the majority of women with screen detected ductal carcinoma in situ (DCIS) and breast-conserving surgery is now widely advocated. In this study, biopsy cavity shavings were used to ensure complete excision in 129 women undergoing breast-conserving surgery for screen detected DCIS. A margin was considered clear if DCIS was > 1 mm from any margin of excision and shavings were clear. Patients with involved margins (DCIS at resection margin) underwent re-excision, irrespective of shaving status. After re-excision, 101 women (78%) had clear margins and 28 (22%) close margins (DCIS < or = 1 mm from resection margin). Cavity shavings were histologically clear of DCIS in all cases. Ipsilateral DCIS recurrence occurred in 12 (9.3%) patients. Two recurrences also contained invasive carcinoma. The median time to diagnosis was 14 months and all recurrences occurred at the site of the previous biopsy. Seven recurrences were detected at the first annual mammogram, four at the second and one at the third. Ipsilateral recurrence was related to margin status; only 2 out of 101 (2%) patients with clear margins recurred, compared with 10 out of 28 (36%) patients with close margins. Local recurrence and close margin status both correlated with a high modified Van Nuys prognostic index score. Our results indicate that local relapse represents residual DCIS rather than true recurrence in the majority of cases. Cavity shavings have proved ineffective in ensuring complete excision. We now ensure a minimum 10 mm margin of excision around all screen-detected DCIS lesions.

Screen-detected breast cancers are smaller than those detected in symptomatic populations and, for any given size, they are associated with fewer lymph node metastases. The management of axillary lymph nodes in patients with screen-detected breast cancer remains controversial. We have previously reported that prevalence (initial screen)-detected cancers are associated with nodal metastases in 17.4% of cases overall. Cancers < or = 10 mm, of any grade, are associated with metastases in only 5% of cases, and grade I cancers

Instruments have been developed for the in situ measurement of concentration and productivity of bottom ice algal layers in Resolute Passage, eastern Canadian Arctic. Measurements are accomplished by deploying an instrument on an arm articulated remotely through a hole in the ice, sampling the subice surface, and finally recovering the instrument and sample. The first instrument is an incubation system that is used to measure in situ productivity of a subice core. Results show the extent and range of productivity in bottom ice, with low and high biomass at the commencement of the algal bloom and near the end of the bloom period, respectively. The second instrument is a reflectance meter that can be used to measure chlorophyll profiles at the subice surface. The meter was calibrated against measured chlorophyll concentrations of extracted cores. After calibration the instrument can be used to measure integrated chlorophyll (milligrams per square metre) and profiles (milligrams per cubic metre) rapidly and synoptically. Deployment of the arm coupled with a plankton pump sampler is also briefly described.

Narrow bandwidth operation of a free electron laser (FEL) at the University of California at Santa Barbara (UCSB) by seed injection from an external continuous wave molecular laser has been demonstrated. The pulse-to-pulse frequency bandwidth was reduced by one order of magnitude, from 1.6 to 0.16 GHz and an order of magnitude reduction of the sideband mode beating was observed in a single pulse together with a 30% reduction in laser startup time. Numerical simulations of the multimode FEL show that in normal operation of the UCSB FEL sideband mode suppression is rather slow underlining the importance of seeding to obtain single-mode operation for the available pulse length.

Narrow-bandwidth operation of a quasicontinuous free-electron laser by seed injection has been demonstrated. The pulse-to-pulse frequency bandwidth has been reduced from 1.6 to 0.16 GHz. An order-of-magnitude reduction of the sideband-mode beating in a single pulse and a 30% reduction in laser start-up time has been obtained. Numerical simulations of the multimode free-electron laser show that the sideband-mode suppression and the buildup of coherence are rather slow, underlining the importance of seeding to obtain single-mode operation for the available pulse length.

Background & Aims Minimal hepatic encephalopathy (MHE) is difficult to diagnose. The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed MHE with 90% sensitivity and specificity in a selected population; high lure and low target rates indicated poor ICT performance. We studied the reliability and validity of ICT for MHE diagnosis. Methods ICT was compared with a psychometric battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic encephalopathy (OHE) prediction. ICT was administered twice for test-retest reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS), and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to administer ICT was recorded and compared with that of a psychologist for cost analysis. Results One hundred thirty-six cirrhotic patients and 116 age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity for MHE diagnosis with 0.902 area under the curve for receiver operating characteristic. MHE-positive patients had significantly higher ICT lures (11 vs 4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P = .0001) compared with MHE-negative patients. The test/retest reliability for ICT lures (n = 50, r=0.90, P = .0001) was high. ICT and SPT were equivalent in predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs 9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10 vs 5, respectively; P = .002). The MAs were successfully trained to administer ICT; the time required for test administration and the associated costs were smaller for ICT than for SPT. Conclusions ICT is a sensitive, reliable, and valid test for MHE diagnosis that can be administered inexpensively by MAs.

Purpose To evaluate the likelihood of successful retrieval of the Gunther Tulip vena cava filter after various implant durations (up to 494 days). Materials and Methods Retrievable Gunther Tulip filters were placed in 554 patients. All patients satisfied requirements for filter placement; the primary indication for placement was specified for 394 patients (71%), as follows: unspecified trauma ( n = 164), bariatric procedures ( n = 128), orthopedic procedures ( n = 36), and other ( n = 66). Filter tilt and vena cava injury were assessed at implantation. Filters were not repositioned after placement. At retrieval, filter orientation, vena cava injury, other device-related incidents, and the degree of difficulty associated with retrieval were reported. Results Filter retrieval was attempted in 275 patients and successful in 248 (90.2%). The mean filter indwell time was 58.9 days (range, 3–494 days). Unsuccessful retrievals ( n = 27) were attributed primarily to improper hook orientation ( n = 10) or excessive tissue in-growth at the filter legs ( n = 16). Of the remaining 279 patients, 223 withdrew from the study, 41 were associated with a decision to keep the filter as a permanent device, 13 died for reasons unrelated to the study, and two had no reported endpoint data. A Kaplan-Meier product-limit survival estimate revealed that the probability of successful device retrieval remained greater than 94% at 12 weeks and greater than 67% at 26 weeks. Conclusions This study contributes to the body of clinical data related to retrievable filters, demonstrating reliable retrieval rates at 12 weeks, with successful retrievals up to 17 months after implantation.

Clostridium difficile-associated disease has increased significantly in North American medical centers. The impact of C difficile on patients with IBD (Crohn's disease, ulcerative colitis) at the present time is unknown.A retrospective, observational study evaluating IBD patients followed in a referral center to evaluate the impact of C difficile was performed. Diagnosis was confirmed with stool toxin analysis. Demographic information, diagnosis, anatomic location, IBD therapy, antibiotic exposure, hospitalizations, and surgeries were recorded. Available endoscopic and histologic data were evaluated.Rate of C difficile infection increased from 1.8% of IBD patients in 2004 to 4.6% in 2005 (P.01). Proportion of IBD patients within the total number of C difficile infections at our institution increased from 7% in 2004 to 16% in 2005 (P.01). IBD colonic involvement was found in the majority of C difficile-infected patients in 2005 (91%), and the majority contracted infection as an outpatient (76%). Antibiotic exposure was identified in 61% of IBD patients with C difficile infection in 2005. Pseudomembranes and fibrinopurulent eruptions were not seen endoscopically or histologically. During 2004-2005 more than half of the infected IBD patients required hospitalization, and 20% required colectomy. Univariate and multivariate analysis identified maintenance immunomodulator use and colonic involvement as independent risk factors for C difficile infection in IBD.C difficile infection has increased significantly in IBD patients and negatively impacts clinical outcome. Increased vigilance regarding this infection in IBD patients with colitis activity is warranted.