Emergence of a compositional neural code for written words: Recycling of a convolutional neural network for reading.

The visual word form area (VWFA) is a region of human inferotemporal cortex that emerges at a fixed location in the occipitotemporal cortex during reading acquisition and systematically responds to written words in literate individuals. According to the neuronal recycling hypothesis, this region arises through the repurposing, for letter recognition, of a subpart of the ventral visual pathway initially involved in face and object recognition. Furthermore, according to the biased connectivity hypothesis, its reproducible localization is due to preexisting connections from this subregion to areas involved in spoken-language processing. Here, we evaluate those hypotheses in an explicit computational model. We trained a deep convolutional neural network of the ventral visual pathway, first to categorize pictures and then to recognize written words invariantly for case, font, and size. We show that the model can account for many properties of the VWFA, particularly when a subset of units possesses a biased connectivity to word output units. The network develops a sparse, invariant representation of written words, based on a restricted set of reading-selective units. Their activation mimics several properties of the VWFA, and their lesioning causes a reading-specific deficit. The model predicts that, in literate brains, written words are encoded by a compositional neural code with neurons tuned either to individual letters and their ordinal position relative to word start or word ending or to pairs of letters (bigrams).

The role of area deprivation index in health care disruptions among cancer survivors during the SARS-CoV-2 pandemic.

OBJECTIVE: To examine the associations between demographic/medical and geographic factors with follow-up medical care and health-related quality of life (HRQoL) among cancer survivors during the SARS-CoV-2 pandemic. STUDY DESIGN: Cross-sectional survey. METHODS: An online survey was sent to cancer survivors between May 2020 and January 2021, exploring their experience with SARS-CoV-2, follow-up care, and HRQoL. PolicyMap was used to geocode home addresses. Both geographic and demographic/medical factors were examined for their associations with SARS-CoV-2 experience, follow-up care, and HRQoL (FACT-G7). RESULTS: Geographic data were available for 9651 participants. Patients living in the highest area deprivation index (ADI) neighborhoods (most deprived) had higher odds of avoiding in-person general (odds ratio [OR] = 7.20; 95% confidence interval [CI] = 2.79-18.60), cancer (OR = 8.47; 95% CI = 3.73-19.30), and emergency (OR = 14.2; 95% CI = 5.57-36.30) medical care, as well as lower odds of using telemedicine (OR = 0.61; 95% CI = 0.52-0.73) compared to the lowest ADI group. Race/ethnicity was not associated with follow-up care after controlling for ADI. The effect of ADI on HRQoL was generally in the expected direction, with higher ADI being associated with worse HRQoL. CONCLUSIONS: ADI influenced follow-up medical care more than age, race/ethnicity, or health insurance type. Healthcare providers and institutions should focus on decreasing barriers to in-person and telemedicine health care that disproportionally impact those living in more deprived communities, which are exacerbated by health care disruptions like those caused by the SARS-CoV-2 pandemic.

Complete mesocolic excision versus standard resection for colon cancer: a systematic review and meta-analysis of perioperative safety and an evaluation of the use of a robotic approach.

PURPOSE: Complete mesocolic excision (CME) has been associated with improved oncological outcomes in treatment of colon cancer. However, widespread adoption is limited partly because of the technical complexity and perceived risks of the approach. The aim of out study was to evaluate the safety of CME compared to standard resection and to compare robotic versus laparoscopic approaches. METHODS: Two parallel searches were undertaken in MEDLINE, Embase and Web of Science databases 12 December 2021. The first was to evaluate IDEAL stage 3 evidence to compare complication rates as a surrogate marker of perioperative safety between CME and standard resection. The second independent search compared lymph node yield and survival outcomes between minimally invasive approaches. RESULTS: There were four randomized control trials (n = 1422) comparing CME to standard resection, and three studies comparing laparoscopic (n = 164) to robotic (n = 161) approaches. Compared to standard resection, CME was associated with a reduction in Clavien-Dindo grade 3 or higher complication rates (3.56% vs. 7.24%, p = 0.002), reduced blood loss (113.1 ml vs. 137.6 ml, p < 0.0001) and greater mean lymph node harvest (25.6 vs. 20.9 nodes, p = 0.001). Between the robotic and laparoscopic groups, there were no significant differences in complication rates, blood loss, lymph node yield, 5-year disease-free survival (OR 1.05, p = 0.87) and overall survival (OR 0.83, p = 0.54). CONCLUSIONS: Our study demonstrated improved safety with CME. There was no difference in safety or survival outcomes between robotic and laparoscopic CME. The advantage of a robotic approach may lie in the reduced learning curve and an increased penetration of minimally invasive approach to CME. Further studies are required to explore this. PROSPERO ID: CRD42021287065.

Abnormal brain function in photophobic patients with dry eye disease: An fMRI study.

BACKGROUND AND OBJECTIVES: Photophobia, a frequent and disabling symptom observed in various neurological conditions and eye diseases, is thought to involve maladaptive brain functioning. We assessed this hypothesis, using functional magnetic resonance imaging (fMRI) in photophobic patients with minimal-to-severe dry eye disease (DED), as compared to healthy controls. METHODS: This prospective, monocentric, comparative, cohort study included eleven photophobic DED patients compared to eight controls. Photophobic patients had a complete evaluation of DED to exclude any other cause of photophobia. All participants were scanned with fMRI under intermittent light stimulation with a LED lamp (27s. ON, 27 s. OFF), and cerebral activations were studied with univariate contrasts between the ON and OFF conditions, and with functional connectivity methods. RESULTS: Firstly, stimulation activated the occipital cortex more strongly in patients than in controls. Moreover, stimulation deactivated the superior temporal cortex in patients less than in controls. Secondly, functional connectivity analysis showed that light stimulation induced lesser decoupling between the occipital cortex and the salience and visual networks in patients than in controls. DISCUSSION: The current data shows that DED patients with photophobia have maladaptive brain anomalies. There is hyperactivity in the cortical visual system, associated with abnormal functional interactions, both within the visual cortex, and between visual areas and salience control mechanisms. Such anomalies show similarities with other conditions such as tinnitus, hyperacusis, and neuropathic pain. Those findings support novel neurally oriented methods for the care of patients with photophobia.

Exploratory Study of Low Resolution Electromagnetic Tomography (LORETA) Real-Time Z-Score Feedback in the Treatment of Pain in Patients with Head and Neck Cancer.

Acute pain from mucositis in patients with head and neck cancer (HNC) undergoing radiation therapy (RT) is common, and may not respond well to narcotics. We used low resolution electromagnetic tomography z-score neurofeedback (LFBz) to investigate whether patients could modify brain wave activity associated with acute pain and whether this would reduce the experience of pain. HNC patients scheduled for RT had baseline pre-pain onset measures (EEG and numeric rating scale) collected before RT and then at pain onset before using analgesics, after each LFBz session and at the end of RT. Up to six sessions of LFBz training were offered over the remaining RT. Up to six 20-min sessions of LFBz were offered over the remaining RT. Data were collected before and after each LFBz session and at the end of RT. Seventeen patients recruited; fourteen were treated and reported decreased pain perception. LFBz allowed patients to modify their brain activity in predesignated areas of the pain matrix toward the direction of their baseline, pre-pain condition (including Brodmann areas (BAs) 3, 4, 5, 13, 24, and 33). LFBz can modify brain regions relevant for pain and these changes were associated with self-reported decreases in pain perception.

Mental health and parenting stress in mothers of children with diabetes treated in a patient-centred medical home.

BACKGROUND: Mothers of children with diabetes are at-risk for experiencing parenting stress and diminished mental/emotional health. To the best of our knowledge, no studies to date have examined whether there are differences in these outcomes between mothers whose diabetic child is managed in a patient-centred medical home or not. OBJECTIVE: The objective of the present study was to assess whether there were differences in mental health and parenting stress among mothers whose diabetic child was managed in a patient-centred medical home or not. METHODS: Two hundred fifty-three mothers of children with diabetes (mean age = 12.50 years; SD = 3.90) from the 2011-2012 National Survey of Children's Health were included in this study. Hierarchical multiple regression was conducted to determine the amount of variance that having a patient-centred medical home contributed to maternal emotional/mental health and parenting stress. RESULTS: After controlling for child sex, age, race/ethnicity and family poverty level, patient-centred medical home status was associated with better mental health for mothers and less parenting stress. Effective care coordination was the only subcomponent of the patient-centred medical home that significantly contributed to the variance in mother's mental/emotional health and parenting stress. CONCLUSIONS: Receiving care in a patient-centred medical home, particularly the care coordination component, may mitigate some of the negative maternal effects of managing a child's diabetes.

Repetitive antidotal treatment is crucial in eliminating eye pathology, respiratory toxicity and death following whole-body VX vapor exposure in freely moving rats.

Exposure to the chemical warfare nerve agent VX is extremely toxic, causing severe cholinergic symptoms. If not appropriately treated, death ultimately ensues. Based on our previously described whole-body vapor exposure system, we characterized in detail the clinical outcome, including respiratory dynamics, typical of whole-body exposure to lethal doses of VX vapor in freely moving rats. We further evaluated the efficacy of two different antidotal regimens, one comprising a single and the other repeated administration of antidotes, in countering the toxic effects of the exposure. We show that a 15 min exposure to air VX concentrations of 2.34-2.42 mg/m3 induced a late (15-30 min) onset of obvious cholinergic signs, which exacerbated over time, albeit without convulsions. Marked eye pathology was observed, characterized by pupil constriction to pinpoint, excessive lacrimation with red tears (chromodacryorrhea) and corneal damage. Respiratory distress was also evident, characterized by a three-fourfold increase in Penh values, an estimate of lung resistance, and by lung and diaphragm histological damage. A single administration of TAB (the oxime TMB-4, atropine and the anticholinergic and antiglutamatergic benactyzine) at the onset of clinical signs afforded only limited protection (66% survival), with clinical deterioration including weight loss, chromodacryorrhea, corneal damage, increased airway resistance and late death. In contrast, a combined therapy of TAB at the onset of clinical signs and repeated administration of atropine and toxogonin (ATOX) every 3-5 h, a maximum of five i.m. injections, led to 100% survival and a prompt recovery, accompanied by neither the above-described signs of eye pathology, nor by bronchoconstriction and respiratory distress. The necessity of recurrent treatments for successful elimination of VX vapor toxicity strongly supports continuous penetration of VX following termination of VX vapor exposure, most likely from a VX reservoir formed in the skin due to the exposure. This, combined with the above-described eye and respiratory pathology and absence of convulsions, are unique features of whole-body VX vapor exposure as compared to whole-body vapor exposure to other nerve agents, and should accordingly be considered when devising optimal countermeasures and medical protocols for treatment of VX vapor exposure.

Commentary: Challenges and Opportunities for Women in Dental Research.

This commentary integrates and expands on the preceding articles in this issue that document and celebrate a century of women's achievements in the International Association for Dental Research (IADR). The increasing participation and leadership of women in dental and craniofacial research and within the IADR were viewed from the perspective of a changing culture of science. The steps that have been taken by the IADR to develop greater inclusiveness are acknowledged, and some of the challenges that remain are discussed in terms of obstacles that are most often social or cultural in origin. Comparisons are made across countries, and the social determinants that lead to differences in women's participation are described. Recommendations are made for developing strategies to change elements of our institutional cultures that have provided advantages to some groups of researchers more than to others. The unconscious biases and a lack of commitment to diversity, equity, and inclusion that limit the participation of members of some groups limit the progress and achievements of science in general.

Gender Inequalities in the Dental Workforce: Global Perspectives.

The aim of this review is to investigate the growth of diversity and inclusion in global academic dental research with a focus on gender equality. A diverse range of research methodologies were used to conduct this review, including an extensive review of the literature, engagement of key informants in dental academic leadership positions around the world, and review of current data from a variety of national and international organizations. Results provide evidence of gender inequalities that currently persist in dental academics and research. Although the gender gap among graduating dental students in North America and the two most populous countries in Europe (the United Kingdom and France) has been narrowed, women make up 30% to 40% of registered dentists in countries throughout Europe, Oceania, Asia, and Africa. In academic dentistry around the globe, greater gender inequality was found to correlate with higher ranking academic and leadership positions in the United States, United Kingdom, several countries in European Union, Japan, and Saudi Arabia. Further disparities are noted in the dental research sector, where women make up 33% of dental researchers in the European Union, 35% in North America, 55% in Brazil, and 25% in Japan. Family and societal pressures, limited access to research funding, and lack of mentoring and leadership training opportunities are reported as also contributing to gender inequalities. To continue advancing gender equality in dental academia and research, efforts should be geared toward the collection and public dissemination of data on gender-specific distributions. Such evidence-driven information will guide the selection of future strategies and best practices for promoting gender equity in the dental workforce, which provides a major pipeline of researchers and scholars for the dental profession.

Detection of copy number variations in epilepsy using exome data.

Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

Prenatal course of metaphyseal anadysplasia associated with homozygous mutation in MMP9 identified by exome sequencing.

Metaphyseal anadysplasia (MANDP) is a rare autosomal recessive form of skeletal dysplasia characterized by normal length at birth and transitory bowing of the legs. Although several families with MANDP have been reported, homozygous mutations in the matrix metalloproteinase type 9 (MMP9) gene have been described in only one consanguineous family, and thus the pre and postnatal phenotypic spectrum is still obscure. A clinically similar but more severe type is caused by autosomal-dominant inheritance and is caused by mutations in matrix metalloproteinase type 13 gene (MMP13). Here, we report the prenatal and early postnatal course of two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses suggesting a diagnosis of MANDP. We propose that MANDP should be considered in pregnancies with early prenatal shortening of the long bones without associated finding of lethal skeletal dysplasias. In addition, the finding of homozygous mutation in non-consanguineous parents of Jewish-Caucasus ancestry may suggest unawareness of such relation or the occurrence of a founder mutation in this gene.

Prevalence and risk factors for left ventricular diastolic dysfunction in a scleroderma cohort.

OBJECTIVES: Left ventricular diastolic dysfunction (LVDD) is more common in systemic sclerosis (SSc) compared to the general population. Focal myocardial ischaemia and fibrosis may be important in its pathogenesis. LVDD is associated with increased mortality and little is known about the risk factors. Advanced SSc lung complications may accompany LVDD. METHOD: We conducted a cross-sectional study of 300 SSc outpatients with and without LVDD, seen between May 2012 and May 2014, and performed univariate and multivariate regression analyses to determine clinical factors associated with LVDD. LVDD was confirmed by the latest echocardiogram (tissue Doppler imaging) reports. Interstitial lung disease (ILD) was confirmed by high-resolution computed tomography (HRCT) and pulmonary hypertension (PH) was diagnosed by right heart catheterization (RHC). RESULTS: Of the 300 SSc patients, there were 133 (44%) with LVDD. In the univariate analysis, advanced age, disease duration (from the onset of Raynaud's phenomenon), anti-centromere antibody, the presence of SSc lung complications, systemic hypertension, smoking, valvular heart disease, chronic kidney and thyroid diseases were all significantly associated with LVDD. However, in the multivariate regression analysis, advanced age was the most significant factor associated with LVDD, followed by systemic hypertension and SSc lung complications. There were significantly more deaths in the LVDD group (p < 0.0001). CONCLUSIONS: LVDD was more prevalent in the SSc population, especially in those with advanced age, systemic hypertension, or SSc-pulmonary complications. SSc patients with pulmonary fibrosis or pulmonary hypertension had more advanced LVDD and higher mortality. More effective therapy is needed to improve the outcome in this population.

Graphene gas sensing using a non-contact microwave method.

We report a non-contact CVD graphene gas sensing method that utilises a high Q microwave dielectric resonator perturbation technique. A graphene sample is coupled to the evanescent field of a dielectric resonator whereupon nitrogen dioxide (NO2), a p-doping gas, is detected by monitoring the change in the linewidth and frequency of the resonant mode. The resonant peak shape is dependent on the number of carriers in the graphene sheet. Therefore, the linewidth perturbation can be converted to a measurement of the graphene sheet resistance. To demonstrate the strength of this technique, sensor response curves for NO2 at different concentrations and temperatures are measured showing sub ppm sensitivity. This technique eliminates interactions between the trace gas and metal contacts that otherwise effect the sensor response of the graphene device.

Genetic and environmental associations between body dissatisfaction, weight preoccupation, and binge eating: Evidence for a common factor with differential loadings across symptom type.

OBJECTIVE: Prior twin studies provide support for a single "common factor" that contributes genetic and environmental risk to a range of disordered eating symptoms. However, the common factor may be indexed less well by binge eating (BE) than other symptoms of eating disorders [i.e., body dissatisfaction (BD) and weight preoccupation (WP)]. We sought to explore the presence of a common factor and test whether loadings differed across three key symptoms (i.e., BE, BD, WP). METHOD: Disordered eating was assessed via self-report in 631 female twin pairs from the Michigan State University Twin Registry. RESULTS: We detected a common disordered eating factor that was influenced primarily by additive genetic and nonshared environmental influences. However, we observed different loadings on this common factor by symptom type, as factor loadings for BD and WP were stronger than that for BE. Moreover, the residual environmental and/or genetic variances (i.e., those that are independent of the common factor) were larger in BE than those of BD or WP. DISCUSSION: Although all three symptoms share a common set of genetic and environmental influences, risk for BE may involve additional genetic, biological, and environmental factors that are not shared with other symptoms of eating pathology. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:157-161).

Validation of an online risk calculator for the prediction of anastomotic leak after colon cancer surgery and preliminary exploration of artificial intelligence-based analytics.

BACKGROUND: Recently published data support the use of a web-based risk calculator ( www.anastomoticleak.com ) for the prediction of anastomotic leak after colectomy. The aim of this study was to externally validate this calculator on a larger dataset. METHODS: Consecutive adult patients undergoing elective or emergency colectomy for colon cancer at a single institution over a 9-year period were identified using the Binational Colorectal Cancer Audit database. Patients with a rectosigmoid cancer, an R2 resection, or a diverting ostomy were excluded. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve (AUROC) was derived and compared with that of the American College of Surgeons National Surgical Quality Improvement Program® (ACS NSQIP) calculator and the colon leakage score (CLS) calculator for left colectomy. Commercially available artificial intelligence-based analytics software was used to further interrogate the prediction algorithm. RESULTS: A total of 626 patients were identified. Four hundred and fifty-six patients met the inclusion criteria, and 402 had complete data available for all the calculator variables (126 had a left colectomy). Laparoscopic surgery was performed in 39.6% and emergency surgery in 14.7%. The anastomotic leak rate was 7.2%, with 31.0% requiring reoperation. The anastomoticleak.com calculator was significantly predictive of leak and performed better than the ACS NSQIP calculator (AUROC 0.73 vs 0.58) and the CLS calculator (AUROC 0.96 vs 0.80) for left colectomy. Artificial intelligence-predictive analysis supported these findings and identified an improved prediction model. CONCLUSIONS: The anastomotic leak risk calculator is significantly predictive of anastomotic leak after colon cancer resection. Wider investigation of artificial intelligence-based analytics for risk prediction is warranted.

User survey of Nanny Angel Network, a free childcare service for mothers with cancer.

PURPOSE: The purpose of the present study was to determine user satisfaction with Nanny Angel Network (nan), a free childcare service for mothers undergoing cancer treatment. METHODS: All 243 living mothers who had used the nan service were invited by telephone to participate in an online research survey; 197 mothers (81%) consented to participate. The survey, sent by e-mail, consisted of 39 items divided into these categories: demographics, supports, use, satisfaction, and general comments. RESULTS: Of the 197 mothers who consented to receive the e-mailed survey, 104 (53%) completed it. More than 90% of the mothers were very satisfied with the help and support from their Nanny Angel. Many mothers mentioned that the Nanny Angel was most helpful during treatment and medical appointments, with 75% also mentioning that their Nanny Angel helped them to adhere to their scheduled medical appointments. However, 64% felt that they had not received enough visits from their Nanny Angel. CONCLUSIONS: Satisfaction with the nan childcare provider was high, but mothers wished the service had been available to them more often. Our study highlights the importance of providing childcare to mothers with inadequate support systems, so as to allow for greater adherence to treatment and medical appointments, and for more time to recover.

Models to Tailor Brain Stimulation Therapies in Stroke.

A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke.

Formal evaluation of PYNK: Breast Cancer Program for Young Women-the patient perspective.

PURPOSE: The aim of the present study was to assess patient satisfaction with pynk: Breast Cancer Program for Young Women so as to determine how the program might be improved and to provide feedback to donors. METHODS: All pynk patients who had consented to have their information entered in our database and who supplied us with their e-mail address were invited to complete a 58-item online questionnaire consisting of multiple choice and open-ended questions. Domains included demographics, provision of written and spoken information, support, infertility risk, research awareness, attitudes toward discharge, and general feedback. RESULTS: Of 120 pynk patients approached, 61 (51%) participated. More than 90% were satisfied or very satisfied with the timing, usefulness, and clarity of spoken and written information given, and 69% found the service and support provided by the nurse navigator to be the most helpful component of the program. Of those who had received systemic therapy, 93% recalled a health care provider initiating a discussion of the risk of treatment-related infertility, and 67% were referred to a fertility clinic. On the negative side, 11%-27% were unaware of various services provided by pynk, and 11% were unaware of pynk's ongoing research. One third of patients were unhappy or ambivalent about the prospect of discharge from the program. CONCLUSIONS: Patient satisfaction with this novel program for young women with breast cancer is high. This study highlights the critical role that the nurse navigator plays in patient support and dissemination of information. In contrast to other reported surveys of young cancer patients, pynk patients are routinely given the opportunity to undergo fertility preservation.

A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493), a folate receptor targeted chemotherapeutic agent in humans with advanced solid tumors.

Background The folate receptor alpha is selectively over-expressed in a number of human cancers. BMS-753493 is a folate conjugate of the epothilone analog BMS-748285 that was designed to selectively target folate receptor expressing cancer cells. Methods BMS-753493 was investigated in two parallel multi-institutional first-in-human phase I/IIa studies in patients with advanced solid tumors. In Study 1, patients were treated on a schedule of once daily dosing of BMS-753493 administered on Days 1, 4, 8 and 11 every 21 days with a starting dose of 5 mg daily and in Study 2, patients were treated once daily on Days 1-4 every 21 days, with a starting dose of 2.5 mg daily. Results A total of 65 patients were treated across the two studies. The maximum tolerated dose (MTD) was 26 mg in Study 1 and 15 mg in Study 2. Fatigue, transaminitis, gastrointestinal toxicity, and mucositis were dose-limiting toxicities. One patient in Study 2 developed Stevens-Johnson syndrome attributed to BMS-753493. Plasma exposures of both the conjugated and free epothilone increased in a dose related fashion in both studies and the half-life of the conjugated epothilone was 0.2-0.6 h across dose levels. No objective tumor responses were seen in either study. Conclusions BMS-753493 was generally tolerable and toxicities known to be associated with epothilone class of anticancer agents were common, although peripheral neuropathy and neutropenia appear to have been less frequent and less severe as compared to epothilones. Antitumor activity was not demonstrated and further development of BMS-753493 has been discontinued.

Risk factors and prognostic scale for cytomegalovirus (CMV) infection in CMV-seropositive patients after allogeneic hematopoietic cell transplantation.

AIM: We aimed to study the risk factors for first and subsequent cytomegalovirus (CMV) infection among patients who are CMV seropositive and underwent allogeneic hematopoietic cell transplantation (HCT). METHODS: We performed an historical cohort study of all sequential CMV-seropositive patients who underwent allogeneic HCT at a single center. Between May 2007 and December 2012, 121 patients fulfilled inclusion criteria. RESULTS: Multivariate model identified myeloablative preparative regimen (hazard ratio [HR] = 4.297, P = 0.033) and acute graft-versus-host disease (GVHD) prior to infection (HR = 5.091, P = 0.021) as risk factors for first CMV infection. The cumulative incidences of first CMV infection for patients with 0, 1, and 2 risk factors were 52%, 71%, and 91%, respectively. Multivariate analysis identified the diagnosis of lymphoma/myeloma (HR = 3.5, P = 0.049) and GVHD (HR = 1.280, P = 0.045) as risk factors for subsequent CMV infection. High graft CD3 stem cell dose was associated with a trend of lower rate of subsequent CMV infection (HR = 0.543, P = 0.056). The cumulative incidences for subsequent CMV infection in patients with 0, 1, and 2-3 risk factors were 11%, 41%, and 77%, respectively. CONCLUSION: In conclusion, in CMV-seropositive patients, myeloablative conditioning and acute GVHD are risk factors for first CMV infection, while lymphoma/myeloma, ongoing GVHD, and low CD3 graft content are risk factors for subsequent infection.