The middle house or the middle floor: Bisecting horizontal and vertical mental number lines in neglect

Abstract This study explores the processing of mental number lines and physical lines in five patients with left unilateral neglect. Three tasks were used: mental number bisection (‘report the middle number between two numbers’), physical line bisection (‘mark the middle of a line’), and a landmark task (‘is the mark on the line to the left/right or higher/lower than the middle of the line?’). We manipulated the number line orientation purely by task instruction: neglect patients were told that the number-pairs represented either houses on a street (horizontal condition) or floors in a building (vertical condition). We also manipulated physical line orientation for comparison. All five neglect patients showed a rightward bias for horizontally oriented physical and number lines (e.g. saying ‘five’ is the middle house number between ‘two’ and ‘six’). Only three of these patients also showed an upward bias for vertically oriented number lines. The remaining two patients did not show any bias in processing vertical lines. Our results suggest that: (1) horizontal and vertical neglect can associate or dissociate among different patients; (2) bisecting number lines operates on internal horizontal and vertical representations possibly analogous to horizontal and vertical physical lines; (3) at least partially independent mechanisms may be involved in processing horizontal and vertical number lines

Evaluation of Milk Enzymes and Electrolytes, Plasma Metabolites, and Oxidative Status in Twin Cows Milked in an Automatic Milking System or Twice Daily in a Conventional Milking Parlor

The aim of this paper was to evaluate the effects of automatic milking (AM) on milk enzymes and minerals related to mammary epithelial integrity in comparison with twice-daily conventional milking (CM). One cow from each of 6 pairs of twins was assigned to be milked with AM or with CM throughout first lactation. Milk production was recorded and milk samples were collected at 4, 11, 18, 25, 32, and 39 wk of lactation (WOL) to determine fat and protein content, somatic cell count, pH, plasminogen (pl) and plasmin (Pl) activities, Na, K, and Cl. Body condition score was monitored; blood samples were collected to determine energy-related metabolites in the first third of lactation (14 WOL), and plasma oxidative status throughout lactation. Overall mean and standard deviation of milking frequency (MF) in AM were 2.69 and 0.88, respectively. Milk production, fat and protein contents, and somatic cell count did not differ between milking systems. The pl and pl+Pl activities were lesser in AM than in CM. Milk pH was greater in AM than in CM. Milk Na, K, Na/K ratio, and Cl did not differ across the whole lactation. Milk pH had a positive correlation with milk Pl activity (r = 0.41), Na (r = 0.37), and Cl (r = 0.40) concentration, and negative correlation with the log(10) of pl/Pl ratio (r = -0.47). The milk Na/K ratio had a positive correlation (r = 0.55) with milk Pl activity. Milking system (MS) did not seem to affect mammary epithelial permeability. The differences in enzymatic (proteolytic) activity due to the MS, probably related to daily MF, lead one to suppose that the quality of the protein fraction for the cheese-making process was preserved better with AM than with CM, even if differences in pH might negatively interfere. No difference was detected in BCS, and in plasma concentration of triglycerides and nonesterified fatty acids, whereas plasma cholesterol concentration during the first 10 WOL was lesser in AM than CM. Oxidative status, measured by plasma reactive oxygen metabolites and thiol groups, did not differ between MS throughout the whole lactation. These results suggest that early lactation of AM primiparous cows may give rise to crucial situations: for milk production, when a low MF may impair further mammary cell proliferation; for milk quality, if an irregular MF, with prolonged milking intervals, leads to an increased milk pH with increased conversion of pl to Pl

Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n=75) and lung (n=71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (P<0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK:4 cells (P<0.0001). Recovered CTCs were relatively pure (60-70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour

Effects of two different blends of naturally mycotoxin-contaminated maize meal on growth and metabolic profile in replacement heifers

The aim of this trial was to assess the effects of the administration of different combinations of mycotoxins in naturally contaminated maize grains on dairy heifer growth, blood measurements and puberty onset. A total of 35 Friesian female heifers were randomly allotted to three experimental groups from 18-21 to 42-45 weeks of age. During the 24-week experimental period (EP), heifers were fed the same diet, but with maize meal derived from three differently contaminated lots: very low contamination, as control (C); medium-low aflatoxin-contaminated (A); and mixed aflatoxin-fumonisin contaminated (A-F). At the end of the EP, they returned to a common diet without contaminated maize, and they were monitored for an additional period of 12 weeks (post-experimental period, PEP). BW, wither height, hip height, body length and heart girth were measured every 4 weeks from the beginning of EP to the end of PEP. At the same time, body condition score was evaluated and blood samples were taken from the jugular vein to be analysed for haematological, serum protein and metabolic profiles. Age at puberty was assessed by measuring weekly plasma progesterone levels from 40 to 52 weeks of age. Body growth measurements were processed both by ANOVA of average daily gain of EP and PEP separately, and by the analysis of growth curve parameters. Haematological, serum protein and metabolic profile were evaluated using a mixed model, taking into account the repeated measurements in time on each animal. Heifers' growth was delayed both in A and A-F groups during EP, as evidenced by the different linear coefficients of the BW growth curve in the three groups. Differently contaminated diets did not affect the haematological profile, so that it can be concluded that these levels of mycotoxin contamination do not determine any specific effect on haematopoiesis and immunity in growing heifers. The main blood marker of mycotoxin chronic toxicity was the γ-glutamyl transferase activity level in plasma, which appeared to be altered even after the removal of mycotoxins. During EP, plasma glucose was lower in the groups fed contaminated diet compared with C. The joint actions of an altered nutritional status and a long-lasting liver damage were probably the causes of the delay in puberty attainment in A and, particularly, in the A-F group. The results from this trial evidenced that a chronic aflatoxin-fumonisin contamination in diets of dairy heifers can determine an important delay in the reproductive career of these animals

Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model

We have developed a personalized vaccine whereby patient derived leukemia cells are fused to autologous dendritic cells, evoking a polyclonal T cell response against shared and neo-antigens. We postulated that the dendritic cell (DC)/AML fusion vaccine would demonstrate synergy with checkpoint blockade by expanding tumor antigen specific lymphocytes that would provide a critical substrate for checkpoint blockade mediated activation. Using an immunocompetent murine leukemia model, we examined the immunologic response and therapeutic efficacy of vaccination in conjunction with checkpoint blockade with respect to leukemia engraftment, disease burden, survival and the induction of tumor specific immunity. Mice treated with checkpoint blockade alone had rapid leukemia progression and demonstrated only a modest extension of survival. Vaccination with DC/AML fusions resulted in the expansion of tumor specific lymphocytes and disease eradication in a subset of animals, while the combination of vaccination and checkpoint blockade induced a fully protective tumor specific immune response in all treated animals. Vaccination followed by checkpoint blockade resulted in upregulation of genes regulating activation and proliferation in memory and effector T cells. Long term survivors exhibited increased T cell clonal diversity and were resistant to subsequent tumor challenge. The combined DC/AML fusion vaccine and checkpoint blockade treatment offers unique synergy inducing the durable activation of leukemia specific immunity, protection from lethal tumor challenge and the selective expansion of tumor reactive clones

The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

The development of sensitive and non-invasive ‘‘liquid biopsies’’ presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs

Parsing with Structure-Preserving Categorial Grammars

This book is a study of the logical and computational properties of structure-preserving categorial grammars. The first part of the book presents chart-parsers for non-associative categorial grammars in the style of Ajdukiewicz and Bar-Hillel. These are proposed in Chapter 3 as deductive parsers, that is as deductive systems which take advantage of the linear order of the syntactic categories. In Chapter 4 they are formulated as polynomial parsing algorithms. An important aspect is the formulation of efficient methods for handling product formulas in the parsing process. The second part of the book deals with Lambek style categorial grammars. A simple and elegant method for automatic recognition is formulated in Chapter 5 and its syntactic and semantic properties are explored in the subsequent chapters. A surprising result is the connection between the number of semantic readings of a sequent and the binomial coefficient discussed in Chapter 6. The results of polynomiality in Chapter 7 are grounded on explicit algorithms which generalize and improve previous results. The parsing techniques presented in this book are among the first complete applications of chart-parsing methods to logical grammars and lay the ground for a new approach to parsing with type-logical grammars