Nodular Regenerative Hyperplasia Secondary to Neoadjuvant Chemotherapy for Colorectal Liver Metastases

Liver resection is the only curative treatment for patients with colorectal liver metastases (CLMs). Neoadjuvant chemotherapy can improve resectability but has a potential harmful effect on the nontumorous liver. Patients with chemotherapy-induced hepatic injury undergoing liver surgery have higher risks of post-resectional morbidity. We present two cases of patients without pre-existent liver disease treated with oxaliplatin-based chemotherapy followed by surgical resection of their CLMs. Their intra-operative liver specimen showed morphologic abnormalities characteristic of nodular regenerative hyperplasia (NRH). NRH led to portal hypertension in both patients that resulted in deleterious post-resectional complications and death of one patient. Interestingly, the other patient underwent two repeat nonanatomic liver resections because of recurrent CLMs. The intra-operative liver specimen still showed signs of NRH and sinusoidal congestion, but the post-resectional courses were uneventful. Nevertheless, caution is recommended in patients with suspected NRH. Careful volumetric analysis should guide the operative strategy. When future remnant liver volume is regarded insufficient, portal vein embolization or restrictive surgery should be considered

Sitting Behaviors and Mental Health among Workers and Nonworkers: The Role of Weight Status

Objective. To explore the associations between sitting time in various domains and mental health for workers and nonworkers and the role of weight status. Design. Cross-sectional analyses were performed for 1064 respondents (47% men, mean age 59 years) from the Doetinchem Cohort Study 2008-2009. Sedentary behavior was measured by self-reported time spent sitting during transport, leisure time, and at work. Mental health was assessed by the Mental Health Inventory (MHI-5). BMI was calculated based on measured body height and weight. Results. Neither sitting time during transport nor at work was associated with mental health. In the working population, sitting during leisure time, and particularly TV viewing, was associated with poorer mental health. BMI was an effect modifier in this association with significant positive associations for healthy-weight non-workers and obese workers. Conclusion. Both BMI and working status were effect modifiers in the relation between TV viewing and mental health. More longitudinal research is needed to confirm the results and to gain insight into the causality and the underlying mechanisms for the complex relationships among sedentary behaviors, BMI, working status, and mental health

SAFEGUI: resampling-based tests of categorical significance in gene expression data made easy

Summary: A large number of websites and applications perform significance testing for gene categories/pathways in microarray data. Many of these packages fail to account for expression correlation between transcripts, with a resultant inflation in Type I error. Array permutation and other resampling-based approaches have been proposed as solutions to this problem. SAFEGUI provides a user-friendly graphical interface for the assessment of categorical significance in microarray studies, while properly accounting for the effects of correlations among genes. SAFEGUI incorporates both permutation and more recently proposed bootstrap algorithms that are demonstrated to be more powerful in detecting differential expression across categories of genes

Manifolds with small Dirac eigenvalues are nilmanifolds

Consider the class of n-dimensional Riemannian spin manifolds with bounded sectional curvatures and diameter, and almost non-negative scalar curvature. Let r=1 if n=2,3 and r=2^{[n/2]-1}+1 if n\geq 4. We show that if the square of the Dirac operator on such a manifold has $r$ small eigenvalues, then the manifold is diffeomorphic to a nilmanifold and has trivial spin structure. Equivalently, if M is not a nilmanifold or if M is a nilmanifold with a non-trivial spin structure, then there exists a uniform lower bound on the r-th eigenvalue of the square of the Dirac operator. If a manifold with almost nonnegative scalar curvature has one small Dirac eigenvalue, and if the volume is not too small, then we show that the metric is close to a Ricci-flat metric on M with a parallel spinor. In dimension 4 this implies that M is either a torus or a K3-surface

Paediatric motor phenotypes in early-onset ataxia, developmental coordination disorder, and central hypotonia

Aims To investigate the accuracy of phenotypic early-onset ataxia (EOA) recognition among developmental conditions, including developmental coordination disorder (DCD) and hypotonia of central nervous system origin, and the effect of scientifically validated EOA features on changing phenotypic consensus. Method We included 32 children (4-17y) diagnosed with EOA (n=11), DCD (n=10), and central hypotonia (n=11). Three paediatric neurologists independently assessed videotaped motor behaviour phenotypically and quantitatively (using the Scale for Assessment and Rating of Ataxia [SARA]). We determined: (1) phenotypic interobserver agreement and phenotypic homogeneity (percentage of phenotypes with full consensus by all three observers according to the underlying diagnosis); (2) SARA (sub)score profiles; and (3) the effect of three scientifically validated EOA features on phenotypic consensus. Results Phenotypic homogeneity occurred in 8 out of 11, 2 out of 10, and 1 out of 11 patients with EOA, DCD, and central hypotonia respectively. Homogeneous phenotypic discrimination of EOA from DCD and central hypotonia occurred in 16 out of 21 and 22 out of 22 patients respectively. Inhomogeneously discriminated EOA and DCD phenotypes (5 out of 21) revealed overlapping SARA scores with different SARA subscore profiles. After phenotypic reassessment with scientifically validated EOA features, phenotypic homogeneity changed from 16 to 18 patients. Interpretation In contrast to complete distinction between EOA and central hypotonia, the paediatric motor phenotype did not reliably distinguish between EOA and DCD. Reassessment with scientifically validated EOA features could contribute to a higher phenotypic consensus. Early-onset ataxia (EOA) and central hypotonia motor phenotypes were reliably distinguished. EOA and developmental coordination disorder (DCD) motor phenotypes were not reliably distinguished. The EOA and DCD phenotypes have different profiles of the Scale for Assessment and Rating of Ataxia

The structuring of production control systems

Co-ordination of the activities of production units is necessary to realise the required delivery performance in the market. These should not conflict with reaching the production economics objectives of each of the units. Production structure is needed to reduce the complexity and should minimise the loss of potential flexibility. Any structure will have some elements in common — the definition of basic elements (e.g. capacities) as a first step in production control structure design; the introduction of product units and the decomposition of the total production control to Goods Flow Control and Production Unit Control; the relationship of sales and manufacturing and the interference of products and capacities as two main determining factors of the Goods Flow Control structure. The generality of these elements means it is possible to develop a small but relatively complete set of reference structures. A reference structure for Goods Flow Control in a repetitive manufacturing situation is discussed. Its main elements are master planning, material co-ordination, workload control and work order release

Retinal Degeneration Progression Changes Lentiviral Vector Cell Targeting in the Retina

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma:A Prospective Longitudinal Study

Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.</p