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Abstract:This essay analyses the pitfalls of auction catalogs’ descriptions of fragments and cuttings. Through an in-depth examination of a cutting sold through Sotheby’s in 2009, the author deconstructs the way in which such fragments are attributed to well-known scribes or illuminators. The cutting was initially ascribed to the so-called Murano Master, but an investigation of the style and artistic features of the fragment challenges this assumption. The essay critically assesses the illumination of the Sotheby’s cutting to contextualize the role of the artist attribution, artistic quality, and provenance of fragments in auction catalogs.

Individuated font selection, which can increase text reading speed, may be able to increase mathematical expression reading speed and influence reasoning accuracy. To investigate whether the same font that increases a participant’s reading speed enhances mathematical reading, we compared their speed in evaluating mathematical expressions as true or false presented in their fastest reading font as determined by empirical test and with a control font, Times Roman. Participants were faster in completing mathematical problems when using typography selected for individual readability, but no difference occurred in task accuracy, matching patterns previously seen in interlude reading. Future research should assess the impact of elements of time pressure, math complexity, numeric versus text-based questions, and associated math anxiety.

Cardiac wasting is a detrimental consequence of cancer that has been traditionally ignored and often misinterpreted as an iatrogenic effect. We conducted a retrospective study on 42 chemo‐naive patients affected by locally advanced head and neck cancer (HNC). Based on unintentional weight loss, patients were divided into cachectic and non‐cachectic. Left ventricular mass (LVM), LV wall thickness (LVWT), interventricular septal (IVS) thickness, left ventricular internal diameter diastolic (LVIDd), left ventricular internal diameter systolic (LVIDs), internal ventricular septum diastolic (IVSd), left ventricular posterior wall thickness diastolic (LVPWd) and LV ejection fraction (LVEF) were analysed by echocardiography. In parallel, we retrospectively analysed 28 cardiac autoptic specimens of patients who either died of cancer before chemotherapy or with a diagnosis of cancer at autopsy. Presence or absence of myocardial fibrosis at microscopic observation was used for sample stratification. Conventional histology was performed. Cachectic and non‐cachectic patients had a significantly different value of LVWT and IVS thickness and LVPWd. LVWT was 9.08 ± 1.57 versus 10.35 ± 1.41 mm (P= 0.011) in cachectic and non‐cachectic patients, IVS was 10.00 mm (8.50–11.00) versus 11.00 mm (10.00–12.00) (P= 0.035), and LVPWd was 9.0 (8.5–10.0) and 10.00 mm (9.5–11.0) (P= 0.019) in cachectic and non‐cachectic patients. LVM adjusted for body surface area or height squared did not differ between the two populations. Similarly, LVEF did not show any significant decline. At multivariate logistic regression analysis for some independent predictors of weight loss, only LVWT maintained significant difference between cachectic and non‐cachectic patients (P= 0.035, OR = 0.240; P= 0.019). The secondary analysis on autoptic specimens showed no significant change in heart weight, whereas LVWT declined from 9.50 (7.25–11.00) to 7.50 mm (6.00–9.00) in cardiac specimens with myocardial fibrosis (P= 0.043). These data were confirmed in multivariate logistic regression analysis (P= 0.041, OR = 0.502). Histopathological analysis confirmed severe atrophy of cardiomyocytes, fibrosis and oedema as compared with controls. Subtle changes in heart structure and function occur early in HNC patients. These can be detected with routine echocardiography and may help to select appropriate cancer treatment regimens for these patients. Histopathological analysis provided conclusive evidence that atrophy of cardiomyocytes, oedema and fibrosis occur during cancer progression and may precede the onset of overt cardiac pathology. To our knowledge, this is the first clinical study that establishes a direct relationship between tumour progression and cardiac remodelling in HNCs and the first pathological study conducted on human cardiac autopsies from selected chemo‐naïve cancer patients.

Abstract:The Master of the Murano Gradual is one of the most enigmatic illuminators working in early fifteenth-century Venice. The eponymous choir books were commissioned by the Camaldolese monastery of San Mattia a Murano and today comprise a single intact volume in the Kupferstichkabinett in Berlin (MS 78 F.1) and about fifty historiated initials dispersed in twenty-five public and private collections in Europe and the United States. The fragmentary nature of the overall corpus is a central challenge to studying the artist and to understanding the contours of the workshop. This article provides a reassessment of the corpus of work attributed to the Murano Master—including an appendix with provenances of the whereabouts of the series—and makes a case for future collaborations that can build upon digitization efforts that make the fragments available online and upon recent technical analysis into the pigments used by the illuminators.The methodological approach of the authors has been twofold. Firstly, to study each of the fragments and manuscripts in person, and to locate digital assets for as many works as possible with the aim of creating an eventual website or online repository for scholars to consult. Secondly, to investigate codicological features of the individual fragments that have been hitherto overlooked, including the measurement of musical stave heights or blind-ruled lines for song, and the possible relationship between decorated and filigree letters to over one-hundred cuttings with decorated letters that have also been associated with the San Mattia series. Finally, the study also clarifies the dating of the Murano choir books, which were most likely produced in the 1420s.

Purpose: The application of traditional silicon strip detectors in space experiments often suffers from heat and power consumption limitations when a large area has to be instrumented. Recently, a scintillating fiber detector with SiPM readout was proposed and adopted by ground high-energy experiments. Its excellent performance in track measurement and mechanical flexibility makes it a prospective candidate for large-area tracking detectors in the next-generation space experiments. This paper mainly focuses on its performance in cosmic-ray charge measurement. Methods: A fast Geant4 simulation for a single tracker module was developed and compared with the beam test results. The non-uniformity of the detector response was studied. Moreover, a full tracker simulation using a variety of typical cosmic ray nuclei was implemented. The performance of a fiber tracker with multiple layers was evaluated. Results and conclusion: The comparison between the simulation results and the beam test data of protons and helium nuclei shows a good agreement. The non-uniformity study reveals the strong dependence of the detector signal on the position and inclination angle of the incident particles. Then, a corresponding correction algorithm was developed and applied in the following data analysis. The preliminary result shows that the charge measurement capability of the fiber tracker composed of 9 XY superlayers is comparable to that of the AMS-02 inner tracker, which consists of 7 layers of double-sided silicon micro-strip ladders. This paper discusses the feasibility of using fiber trackers to measure cosmic ray charges and provide a guide for the optimization of detector design.

ABSTRACT:Background:Isolated, subtle neurological abnormalities (ISNA) are commonly seen in aging and have been related to cerebral small vessel disease (SVD) and subcortical atrophy in neurologically and cognitively healthy aging subjects.Objective:To investigate the frequency of ISNA in different mild cognitive impairment (MCI) types and to evaluate for each MCI type, the cross-sectional relation between ISNA and white matter hyperintensities (WMH), lacunes, caudate atrophy, and ventricular enlargement.Methods:One thousand two hundred fifty subjects with different MCI types were included in the analysis and underwent brain magnetic resonance imaging. WMHs were assessed through two visual rating scales. Lacunes were also rated. Atrophy of the caudate nuclei and ventricular enlargement were assessed through the bicaudate ratio (BCr) and the lateral ventricles to brain ratio (LVBr), respectively. Apolipoprotein E (APOE) genotypes were also assessed. The routine neurological examination was used to evaluate ISNAs that were clustered as central-based signs, cerebellar-based signs, and primitive reflexes. The items of Part-III of the Unified Parkinson’s Disease Rating Scale were used to evaluate ISNAs that were clustered as mild parkinsonian signs. Associations of ISNAs with imaging findings were determined through logistic regression analysis.Results:The ISNAs increase with the age and are present in all MCI types, particularly in those multiple domains, and carrying the APOE ϵ4 allele, and are associated with WMH, lacunes, BCr, and LVBr.Conclusion:This study demonstrates that cortical and subcortical vascular and atrophic processes contribute to ISNAs. Long prospective population-based studies are needed to disentangle the role of ISNAs in the conversion from MCI to dementia.

Microcephaly is a sign of many genetic conditions but has been rarely systematically evaluated. We therefore comprehensively studied the clinical and genetic landscape of an unselected cohort of patients with microcephaly.

Background: Mild Parkinsonian Signs (MPS) have been associated with Mild Cognitive Impairment (MCI) types with conflicting results. Objective: To investigate the association of individual MPS with different MCI types using logistic ridge regression analysis, and to evaluate for each MCI type, the association of MPS with caudate atrophy, global cerebral atrophy, and the topographical location of White Matter Hyperintensities (WMH), and lacunes. Methods: A cross-sectional study was performed among 1,168 subjects with different types of MCI aged 45-97 (70,52 ± 9,41) years, who underwent brain MRI. WMH were assessed through two visual rating scales. The number and location of lacunes were also rated. Atrophy of the caudate nuclei and global cerebral atrophy were assessed through the bicaudate ratio, and the lateral ventricles to brain ratio, respectively. Apolipoprotein E (APOE) genotypes were also assessed. Using the items of the motor section of the Unified Parkinson’s Disease Rating Scale, tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction were evaluated. Results: Bradykinesia, and gait/balance/axial dysfunction were the MPS more frequently encountered followed by rigidity, and tremor. MPS were present in both amnestic and non-amnestic MCI types, and were associated with WMH, lacunes, bicaudate ratio, and lateral ventricles to brain ratio. Conclusion: MPS are present in both amnestic and non-amnestic MCI types, particularly in those multiple domain, and carrying the APOE 4 allele. Cortical and subcortical vascular and atrophic processes contribute to MPS. Long prospective studies are needed to disentangle the contribution of MPS to the conversion from MCI to dementia.

ABSTRACT:Background:To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects. Objective:To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy. Methods:A total of 1246 NCH subjects aged 45–91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visual rating scales. Lacunes were also rated. Association of nPR with vascular risk factors/diseases and imaging findings was evaluated using logistic regression analysis. Results:nPR were exhibited by 33.1% of subjects and increased with age. Subjects with nPR performed less than subjects without nPR in tests evaluating global cognition, executive functions, attention, and language. Snout reflex was the most common nPR, followed by glabellar tap and palmomental reflex. Glabellar tap was associated with parieto-temporal WMH, BCr, and LVBr; snout reflex was associated with frontal lacunes, temporal WMH, BCr, and LVBr; palmomental reflex was associated with parieto-occipital WMH, basal ganglia lacunes, BCr, and LVBr. Conclusions:This study demonstrates that in NCH aging individuals, nPR are associated with WMH, lacunes, BCr, and LVBr and are probably a warning sign of incipient cognitive decline. Therefore, NCH subjects presenting nPR should manage their vascular risk factors/vascular diseases rigorously in order to prevent or delay progression of small vessel disease, and future neurological and cognitive disabilities.

Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of cases with causative copy number variants in 6 patients (∼10%) and causative sequence variants in 16 established disease genes in 20 patients (∼32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. Notably, we found the recessive gene SPATA5causative in as much as 3% of our cohort, indicating that it may have been underdiagnosed in previous studies. We further support candidacy for neurodevelopmental disorders of four previously described genes (PIK3AP1, GTF3C3, UFC1, and WRAP53), three of which also followed a recessive inheritance pattern. Our results therefore confirm the importance of de novo causative gene variants in EE/DEE, but additionally illustrate the major role of mostly compound heterozygous or hemizygous recessive inheritance and consequently high-recurrence risk.

Background: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral Small Vessel Diseases (SVD) with no univocal results. Objective: The aim of this study was to investigate the cross-sectional relation between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of Neurologically and Cognitively Healthy (NCH) aging individuals. Method: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI. The items of the motor section of the Unified Parkinson's Disease Rating Scale were used to evaluate tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction. Caudate atrophy and global cerebral atrophy were assessed through the bicaudate ratio and the lateral ventricles to brain ratio, respectively. WMH were assessed through two visual rating scales. Lacunes were also rated. Associations of MPS with vascular risk factors/diseases and imaging findings were determined through the logistic regression analysis. Results: Frontal and basal ganglia lacunes, frontal WMH, caudate atrophy, and global cerebral atrophy were associated with bradykinesia. Basal ganglia lacunes, caudate atrophy, and global cerebral atrophy were associated with gait/balance/axial dysfunction. Rigidity was associated with frontal WMH, and tremor with caudate atrophy and global cerebral atrophy. NCH subjects with MPS, performed less than subjects without MPS in tests evaluating global cognition and language. Conclusion: This study demonstrates that in NCH aging individuals, MPS are associated with cortical and subcortical vascular and atrophic changes, and are probably, a warning sign of incipient cognitive decline. Subjects with MPS should manage rigorously cerebral SVD to prevent future physical and cognitive disabilities.

Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies. We found (likely) pathogenic variants of KIF7in 5 out of 9 families, including the original ACLS patients, and delineated 1000 to 4000-year-old Swiss founder alleles. Three of the remaining families had (likely) pathogenic variants in the JBTS gene C5orf42, and one patient had a novel de novo frameshift variant in SHHknown to cause autosomal dominant holoprosencephaly. In accordance with the patients’ craniofacial anomalies, we showed facial midline widening after silencing of C5orf42in chicken embryos. We further supported the link between KIF7, SHH, and C5orf42 by demonstrating abnormal primary cilia and diminished response to a SHH agonist in fibroblasts of C5orf42-mutated patients, as well as axonal pathfinding errors in C5orf42-silenced chicken embryos similar to those observed after perturbation of Shh signaling. Our findings, therefore, suggest that beside the neurodevelopmental features, macrocephaly and facial widening are likely more general signs of disturbed SHH signaling. Nevertheless, long-term follow-up revealed that C5orf42-mutated patients showed catch-up development and fainting of facial features contrary to KIF7-mutated patients.

A cutting taken from a luxurious early fifteenth-century Venetian choir book depicts what some scholars have referred to as a ‘scene of sacrilege,’ or a ‘scene of iconoclasm’ (Musée de Cluny, Cl. 22713). The choir book, to which this cutting once belonged, was part of a series made for the Camaldolese monastery of San Mattia di Murano, located in the Venetian lagoon. Scholarly attempts to identify the figure have neglected important iconographic details in the image as well as the liturgical context in which the image was produced. In this paper, through a close visual reading of certain iconographic and stylistic features, I will suggest that this is not a depiction merely of iconoclasm but of a specific narrative: the rarely depicted legend of the Beirut Miracle, which tells the story of an icon of the crucified Christ that bled miraculously after being attacked by the Jews of the city of Beirut in Lebanon. I will also consider the Cluny cutting in the context of the original Camaldolese liturgy in order to link it with an important thirteenth-century panel painting, featuring the same narrative, and made for another Camaldolese monastery, the abbey church of San Salvatore della Berardenga near Arezzo.

Chromosomal mosaicism, which represents a diagnostic challenge for detection and interpretation, has been described in several genetic conditions. It can contribute to a large phenotypic variation in diseases. At analysis of a well-characterized cohort of 714 patients with neurodevelopmental disorders (NDDs) of unknown etiology using a high-resolution chromosomal microarray platform, we found 2 cases (0.28%) of low-level mosaicism and defined a previously detected extra chromosome in a third patient. Two of the cases were mosaics for segmental imbalances (a partial trisomy 3q26.1q27.3 and a partial monosomy 18q21.2qter with 14.6 and 20% mosaic ratios in lymphocytes, respectively), and 1 was a mosaic for an entire chromosome (trisomy 14, mosaic ratio 20%). Our diagnostic yield is in line with the ratios previously published in patients with intellectual disability. Notably, the partial trisomy 3q26.1q27.3 case is an example of a rare and unusual class of a rearranged neocentric ring chromosome, which can neither be categorized in class I, nor in class II of such rearrangements. Our cases further elucidate the phenotypes related to the aberrations of the specific chromosome segments observed and underline the important role of low-level mosaics in the pathogenesis of NDDs of unknown etiology even in the absence of clinical signs of mosaicism.

This study included 238 good morphology blastocysts, which were transferred after vitrification-warming to 152 women by single blastocyst transfer in Holbæk Fertility Clinic, Denmark. Time-lapse recordings of transferred good morphology blastocysts were reassessed to recognize every abnormal cell division (ACD) from the 1st to the 4th cell cycle. ACDs were distinguished as failed cell divisions and multi-cell divisions.

The purpose of the current study was to evaluate efficacy of techniques adapted from situation awareness research for describing how older adults perceive and understand fall risk factors in the context of daily routine. Eleven older adults watched a video of an older woman performing daily activities. Thirteen intrinsic, extrinsic, and behavioral fall risks were embedded throughout the scenario. The video was periodically frozen/blanked from view while participants answered questions about their understanding of the situation and associated story elements. Participants perceived a variety of fall risk factors but did not necessarily interpret them as indicating fall risk. Many fall risks held non-fall meaning for participants (e.g., newspapers on the floor meant the woman liked to read). Although four participants readily identified a fall risk situation, seven did not until they were explicitly asked to consider safety. Study techniques were effective for describing situation awareness of fall risk and several suggestions for improvement are described.[Res Gerontol Nurs. 2016; 9(4):161–166.]

Labor market dynamics in the US are changing due to long-term factors including decelerating labor force growth, rising age of the labor force, and the rapid advance of e-commerce, as well as the one-time downward adjustment during 2009–2013 of the size of state and local government work forces. We discuss some of the controversies revolving around how to analyze labor markets in this dynamic environment from the perspective of monetary policymaking, given the dual mandate of the Federal Reserve to encourage both full employment and price stability. Our statistical research documents the changing association between US unemployment and core inflation. There was a perceived trade-off between inflation and unemployment in the 1950s and 1960s that gave way to stagflation in the 1970s, when both unemployment and inflation were rising. The 1980s were a transition period where the trade-off was perceived to have returned. This trade-off has not been so clear, however, when one looks at the last twenty years. Since 1995, a period of stable and low inflation was consistently observed despite considerable cycles in the unemployment rate. Our theoretical discussion provides a dynamic interpretation of the shifting nature of labor markets, with the objective of pointing the way for future research while highlighting crucial differences in possible interpretations that could fuel debate, both inside and outside the Fed, over how the Fed should manage its dual mandate. The dynamic changes being seen in US labor markets all suggest that the effectiveness of monetary policy to encourage full employment may be vastly overstated. If this interpretation is correct, the Fed may need to reconsider how to manage its dual mandate and react less aggressively to perceived labor slack that may be due to longer-term structural shifts over which the Fed has no influence.

Biomass burning is a major source of light‐absorbing organic aerosol (brown carbon), but its composition, chemical evolution, and lifetime are not well known. We measured water‐soluble brown carbon absorption from 310 to 500 nm on the National Oceanic and Atmospheric Administration Twin Otter aircraft during flights downwind of western United States wildfires in summer 2019. The sampling strategy was near‐Lagrangian and the plume ages spanned 0–5 hr. Trends in brown carbon mass absorption coefficient with plume age varied between flights, and did not show an exponential decay over these short time scales. The measured absorption spectra were smoothly varying, without identifiable contributions from individual chromophores with structured absorption. Using aerosol tracer ions and reference absorption spectra, the calculated contribution of 4‐nitrocatechol to total absorption was <22 ± 9% and <11 ± 5%, although spectral fitting showed that it may be as low as <1.1% and <0.6% at 365 and 405 nm, respectively. Wildfires are a major source of light‐absorbing particles that affect the Earth's radiative budget, but the lifetime and composition of these particles are not well known. We measured the light absorption and concentration of water‐soluble organic aerosol during aircraft flights through wildfire smoke plumes that were less than 5 hr old. We found that light absorption does not decrease over these short time scales, and may instead increase or remain constant. We examined the absorption spectra and aerosol composition to determine the contribution of individual species to the total absorption by organic aerosol. Dilution‐normalized biomass burning brown carbon showed variable, non‐exponential trends over 5 hr, contrary to recent parameterizationsSpectral fits constrain the contribution of 4‐nitrocatechol to brown carbon absorption to be <1.1% at 365% and <0.6% at 405 nmAbsorption spectra indicate a complex mixture of absorbing compounds without identifiable contributions from individual chromophores Dilution‐normalized biomass burning brown carbon showed variable, non‐exponential trends over 5 hr, contrary to recent parameterizations Spectral fits constrain the contribution of 4‐nitrocatechol to brown carbon absorption to be <1.1% at 365% and <0.6% at 405 nm Absorption spectra indicate a complex mixture of absorbing compounds without identifiable contributions from individual chromophores

When the Federal Reserve was established by the US Congress in 1913, its charter mandated that the new central bank “promote an elastic currency” and the institution was given extraordinary powers to serve as a lender of last resort to the banking system. Congress was reacting to the cycle of financial panics that had beset the country since the Civil War and had worsened with the Panic of 1907. Congress sought to find a remedy to prevent runs on banks turning into full-fledged financial crises. The term “elastic” in the opening words of the charter was intended to underscore the need for a robust banking system that could withstand shocks and not collapse upon itself. There was no mention whatsoever of a dual mandate of promoting price stability and encouraging full employment. With prodding from the US Congress, the Federal Reserve became highly involved in the management of the economy of the United States after WWII, focusing on inflation and full employment objectives. In 1993 Professor John Taylor set forth an elegant and simple framework (aka, the Taylor Rule) for analyzing the interest rate policy of the Federal Reserve in terms of its dual mandate. This paper examines Federal Reserve behavior from the mid-1950s to 2011 through the lens of the Taylor Rule. Our contribution is to use a dynamic linear model with Bayesian inference to update the evolution through time of the key parameters surrounding the inflation and full employment mandates, using only the information available to the Federal Reserve at each point in time. Our findings provide a more nuanced quantitative view than is previously available in the literature of how the Federal Reserve shifted its management of its dual mandate over time and in response to different economic challenges. Moreover, our research leads to serious questions of how Federal Reserve decision making may change in the future, following the financial panic of 2008, pointing toward numerous avenues for new research.

AbstractUsing high-resolution molecular karyotyping with SNP arrays to identify candidate genes for etiologically unexplained intellectual disability, we identified a 32-kb de novo in-frame deletion of the C-terminal helicase domain of the SMARCA2gene in a patient with severe intellectual disability, epilepsy, sparse hair, prominent joints, and distinct facial anomalies. Sequencing of the gene in patients with a similar phenotype revealed de novo missense mutations in this domain in 2 further patients, pointing to a crucial role of the SMARCA2 C-terminal helicase domain. The clinical features observed in all 3 patients are typical of Nicolaides-Baraitser syndrome, an only rarely reported syndrome with mainly moderate to severe intellectual disability. Notably, one of our patients with a p.Gly1132Asp mutation showed typical morphological features but an exceptional good development with borderline overall IQ and learning difficulties, thus expanding the phenotypic spectrum of Nicolaides-Baraitser syndrome.Copyright © 2012 S. Karger AG, Basel

Soil properties are one of the main factors affecting the yield and qualitative value of grapes. Therefore, application of compost in a vineyard may affect grape production and chemical composition of berries. For these reasons, we started a field trial in 2001 to determine the long-term effects of compost application on growth, yield and quality of V. viniferacv. Chardonnay grapes grown in a Tuscan vineyard (Italy). In summary, the results demonstrated that long-term addition of compost to a vineyard can be beneficial to soil characteristics, including organic matter and nitrate content, and had no or limited effects on plant growth and grape quality. Contrasting results were observed for production parameters, however, an average result from the nine years of trials shows that compost application maintained a similar average yield throughout the years, when compared to chemical fertilizers.

Aims and background Metastatic colorectal cancer has a heterogeneous behavior, and a set of patients will have minimal response and rapid disease progression. To understand this heterogeneity, studies have evaluated biological and clinical prognostic factors. Alkaline phosphatase seems to be a key prognostic factor, so we have reviewed the outcomes of our patients with respect to alkaline phosphatase levels.Methods and study design Between January 2003 and December 2008, we treated with the FOLFOX 4 regimen 103 consecutive patients with metastatic colorectal cancer. Thirty-two patients had alkaline phosphatase ≥300 U/l.Results Median time to progression was 4 months for patients with high alkaline phosphatase levels and 8 months for those with low alkaline phosphatase levels. Median overall survival was 8 and 17.5 months, respectively. Only 3 patients in the high alkaline phosphatase group obtained partial response (9.4%) compared to 3 complete responses and 24 partial responses (41.5%) in low alkaline phosphatase group. Toxicity was substantially different, with more grade 3–4 neutropenia, diarrhea and oral mucositis in the high than low alkaline phosphatase group.Conclusions Alkaline phosphatase is an uncomplicated and potent prognostic factor. Patients with high alkaline phosphatase levels had a poor prognosis. Free full text available at www.tumorionline.it

Background Uterine leiomyosarcoma (LMS) is a rare malignancy of mesenchymal tissues and in advanced stages its prognosis is very poor. Surgery followed by radiotherapy and/or chemotherapy is the treatment of choice for advanced disease. Cardiac metastases are very uncommon and only a few cases have been described to date.Case A 55-year-old woman was referred to our center for a uterine LMS with lung metastases at diagnosis. After 3 lines of chemotherapy for persistent lung disease, CT scan showed suspected thrombosis in the right pulmonary vein, along with disease progression in the lungs. The patient started treatment with low-molecular-weight heparin and a fourth line of chemotherapy. After 3 months of therapy, a new CT scan showed a larger thrombus and she underwent a cardiology visit that revealed an intracardiac mass. Submitting the patient to palliative surgery or radiation therapy was not possible because of the aggressiveness of the lung metastases, so she continued chemotherapy, resulting in disease stabilization.Conclusions Surgery is the best option for intracardiac dissemination of uterine LMS, but when this is not possible based on the performance status of the patient and spread of the disease, the combination of chemotherapy and radiotherapy seems to be the best option according to the literature. In our case we treated the patient only with chemotherapy.

An artificial neural network (back propagation neural network) based on morphological and fractal leaf and flower parameters was developed for the characterization of three Banksia integrifoliasubspecies and the identification of nine unnamed morphotypes. Results indicated that the network can be effectively and successfully used to discriminate among morphotypes using simple dedicated instruments, such as a PC and an optical scanner. The new method also as a complementary approach to botanical identification, being capable of separating all the tested Banksia integrifoliaaccessions and of creating associations between the known subspecies and the unnamed accessions.

Ornamental nurseries extensively utilize peat in commercial soilless potting media, but its use as an organic amendment with a superior water holding capacity is challenged by economic and environmental pressures so potential alternatives to peat need to be investigated. In our experiment, commercially available peat-based soilless mixes were amended with increasing composted green waste (CGW) percentages. Results on Photinia X fraseriand Viburnum tinussuggest that CGW could partially substitute peat in containerized nursery production, with a different effectiveness related to species behavior. Viburnumseemed to be less affected by CGW addition (only CGW-based media, T100, showed a significant difference compared to peat-based media, used as control), which on the contrary hardly affected Photiniagrowth in terms of biomass production and quality. On the other hand, a higher CGW content (75% or 100%) also improved plant susceptibility to water shortage. Concluding, peat-based media partially amended with CGW may have positive agronomic and economic consequences for commercial ornamental nursery production.

Background and aims:Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase. hTERT expression and telomerase activity are elevated in most human tumors. Bisphosphonates play an important role in the management of tumors with the secondary involvement of bone. Methods:We investigated the effect on hTERT gene expression of clodronate, alendronate, and pamidronate (from 10- 6M to 10- 5M) on MCF-7 and T47D human breast cancer cells, using real time RT-PCR. Results:At 10- 5M, amino-bisphosphonates (alendronate and pamidronate) inhibited breast cancer cell viability and induced a significant decrease in hTERT gene expression with respect to controls (82% and 71% in MCF-7 cells; 74% and 60% in T47D, p<0.0001). No effect was observed with clodronate. Conclusions:Amino-bisphosphonates down-regulate hTERT gene expression. The role of hTERT is a new finding, which gives an alternative explanation for the direct effect of bisphosphonates on tumor cells.

The oxygen stoichiometry, conductivity, and thermal expansion behavior of lanthanum strontium copper iron oxide (La0.7Sr0.3Cu0.2Fe0.8O3−δ) have been investigated because of its potential application as a cathode material for intermediate temperature solid oxide fuel cells (IT-SOFCs). The relative oxygen non-stoichiometry of La0.7Sr0.3Cu0.2Fe0.8O3−δas a function of pO2has been obtained by solid-state coulometric titration at 800 ≤ T≤ 1000 °C and at 10−13≤ pO2≤ 0.5 atm. Two discontinuities in the pO2dependence of the stoichiometry and unexpected hysteresis effects were observed at the temperatures measured. The electrical conductivity behavior as a function of pO2and temperature was determined and related to the oxygen non-stoichiometry.

Reverse transcription polymerase chain reaction (RT-PCR) of cytokeratin-19 (CK-19) has been widely used to detect small numbers of circulating malignant epithelial cells in the bone marrow or the peripheral blood of patients with breast cancer. However, a high percentage of false positive results has been recorded and conflicting reports question the clinical relevance of this technical approach. We demonstrate that the use of a new nested primer pair for CK-19 RT-PCR avoids false positive results without affecting the sensitivity of the assay. Our experiments were carried out using MCF-7 cells alone or mixed with peripheral blood mononuclear cells (PBMNC) of healthy donors. The results were also validated in a large series of healthy donors and in a preliminary study on a limited number of patients with breast cancer, thus suggesting that our assay is feasible for application in the clinical evaluation of occult malignant epithelial cells.

Objectives:To determine the availability in Canada of different types of hormone replacement therapy (HRT) products, and to compare the availability of HRT products in Canada to their availability in other countries.

On October 29, 2002, Health Canada issued Guidance for Industry: Clinical Development of Steroidal Contraceptives Used by Women. The original draft of this guideline, published July 4, 2001, included recommendations for clinical trials in excess of those required in Europe and the United States. The proposed requirements, which reflected Health Canada’s views, had the potential to discourage contraceptive research in Canada and to block registration of new products. To evaluate the impact of Canada’s hormonal contraceptive regulation, a comparative analysis of the availability of products in various countries was performed, along with an evaluation of the time required from submission to approval of a new drug. Women in Canada have access to 35% of the contraceptive products available worldwide and to 37% of the hormonal contraceptives available worldwide, compared with 58% and 59% respectively, in the United States; 52% and 54% respectively, in the United Kingdom; 44% and 54%, respectively, in France; and 44% and 50% respectively, in Sweden. Regarding the more recent contraceptive products available worldwide, women in Denmark have the most choices (67% of available products), whereas women in Canada have the least (only 22% of available products). Eleven of 12 oral contraceptive products recently approved in other countries have either not been submitted for approval in Canada or remain in the Canadian regulatory process. Although the time-to-approval period in Canada, for drugs in general, is 6 months longer than in the United States, the mean lag time for 6 contraceptive products is 29.6 months as of January 1, 2004, and no oral contraceptives have been approved in Canada since 1997.

Results of competency, or certification, tests can have serious consequences for individuals tested, for employers, and for the public. However, the validity of testing outcomes depends not only on the validity of the test's content but also on the validity of the score selected as the passing, or cut-off, score. This article describes procedures and techniques for use by staff development professionals to ensure systematic, rational, and defensible cut-off scores for competency tests.