Covering dimension and finite-to-one maps

Hurewicz' characterized the dimension of separable metrizable spaces by means of finite-to-one maps. We investigate whether this characterization also holds in the class of compact F-spaces of weight c. Our main result is that, assuming the Continuum Hypothesis, an n-dimensional compact F-space of weight c is the continuous image of a zero-dimensional compact Hausdorff space by an at most 2n-to-1 map

Closed copies of N\mathbb{N} in Rω1\mathbb{R}^{\omega_1}

We investigate closed copies of~$\mathbb{N}$ in powers of~$\mathbb{R}$ with respect to $C^*$- and $C$-embedding. We show that $\mathbb{R}^{\omega_1}$ contains closed copies of~$\mathbb{N}$ that are not $C^*$-embedded

Tight bounds on the maximum size of a set of permutations with bounded VC-dimension

The VC-dimension of a family P of n-permutations is the largest integer k such that the set of restrictions of the permutations in P on some k-tuple of positions is the set of all k! permutation patterns. Let r_k(n) be the maximum size of a set of n-permutations with VC-dimension k. Raz showed that r_2(n) grows exponentially in n. We show that r_3(n)=2^Theta(n log(alpha(n))) and for every s >= 4, we have almost tight upper and lower bounds of the form 2^{n poly(alpha(n))}. We also study the maximum number p_k(n) of 1-entries in an n x n (0,1)-matrix with no (k+1)-tuple of columns containing all (k+1)-permutation matrices. We determine that p_3(n) = Theta(n alpha(n)) and that p_s(n) can be bounded by functions of the form n 2^poly(alpha(n)) for every fixed s >= 4. We also show that for every positive s there is a slowly growing function zeta_s(m) (of the form 2^poly(alpha(m)) for every fixed s >= 5) satisfying the following. For all positive integers n and B and every n x n (0,1)-matrix M with zeta_s(n)Bn 1-entries, the rows of M can be partitioned into s intervals so that at least B columns contain at least B 1-entries in each of the intervals.Comment: 22 pages, 4 figures, correction of the bound on r_3 in the abstract and other minor change

Bioresponsive microspheres for on‐demand delivery of anti‐inflammatory cytokines for articular cartilage repair

Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine has shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here, we describe the utility of gelatin microspheres that are responsive to proteolytic enzymes typically expressed in arthritic flares, resulting in on‐demand and spatiotemporally controlled release of anti‐inflammatory cytokines for cartilage preservation and repair. These microspheres were designed with a net negative charge to sequester cationic anti‐inflammatory cytokines, and the magnitude of the negative charge potential increased with an increase in crosslinking density. Collagenase‐mediated degradation of the microspheres was dependent on the concentration of the enzyme. Release of anti‐inflammatory cytokines from the loaded microspheres directly correlated with the degradation of the gelatin matrix. Exposure of the IL‐4 and IL‐13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an OA joint can attenuate the stimulation of chondrocytes and the resulting secretion of catabolic factors such as proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically induced drug release. Consequently, bioresponsive microspheres can be an effective tool for cartilage preservation and arthritis treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/1/jbma36852_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/2/jbma36852.pd

Long-term survival after successful out-of-hospital resuscitation

Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside hospital, of whom 240 (25%) could be discharged alive. A follow-up study was performed to determine prognosis in these patients. Of the 240 survivors of out-of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During the first year, 9% suffered from myocardial (re)infarction and 13% underwent coronary bypass surgery or angioplasty. Within the first 3 years after resuscitation 60% of the patients were readmitted to hospital. Permanent or temporary neurological deficits were observed in 30 patients (14%). Patients with a primary arrhythmia without myocardial infarction had a worse prognosis than patients with a cardiac arrest in the context of an infarct. Survival was better in patients in whom resuscitation was initiated by physicians or ambulance-nurses, than in patients resuscitated by lay-people. Multivariate analysis revealed that this difference could be explained by a larger proportion of patients with a primary arrhythmia in the latter group. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, programmes for resuscitation courses should be stimulated. Such programmes should aim predominantly at relatives of patients with known heart disease, police officers and children

The household economic burden of eating disorders and adherence to treatment in Australia

© 2014 Gatt et al.; licensee BioMed Central Ltd. Background: This study investigated the household economic burden of eating disorders and cost-related non-adherence to treatment in Australia. Methods: Multi-centre prospective observational study using a structured questionnaire. Ninety participants were recruited from two clinic settings in New South Wales, Australia and from the community using social media. The primary outcome measures were household economic burden of illness measured in terms of out-of-pocket expenditure, household economic hardship and cost-related non-adherence. Results: The pattern of out-of-pocket expenditure varied by diagnosis, with Bulimia Nervosa associated with the highest total mean expenditure (per three months). Economic hardship was reported in 96.7% of participants and 17.8% reported cost-related non-adherence. Those most likely to report cost-related non-adherence had a longer time since diagnosis. Cost-related non-adherence and higher out-of-pocket expenditure were associated with poorer quality of life, a more threatening perception of the impact of the illness and poor self-reported health. Conclusions: This study is the first to empirically and quantitatively examine the household economic burden of eating disorders from the patient perspective. Results indicate that households experience a substantial burden associated with the treatment and management of an eating disorder. This burden may contribute to maintaining the illness for those who experience cost-related non-adherence and by negatively influencing health outcomes. Current initiatives to implement sustainable and integrated models of care for eating disorders should strive to minimise the economic impact of treatment on families

PD-L1 immunohistochemistry in non-small-cell lung cancer:unraveling differences in staining concordance and interpretation

Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (p <0.01) improved between EQA schemes from 3.8 (n = 67) to 4.3 (n = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7%) (Dako), SP263 (19.1%) (Ventana), and E1L3N (Cell Signaling) (7.1%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0%) or excessive background staining (19.8%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (p <0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20/423 (4.7%) and 24/423 (5.7%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC

Discrepant Effects of Human Interferon-gamma on Clinical and Immunological Disease Parameters in a Novel Marmoset Model for Multiple Sclerosis

The core pathogenic process in the common marmoset model of multiple sclerosis (MS) is the activation of memory-like T cells specific for peptide 34 to 56 derived from the extracellular domain of myelin/oligodendrocyte glycoprotein (MOG34-56). Immunization with MOG34-56 in incomplete Freund’s adjuvant is a sufficient stimulus for in vivo activation of these T cells, together with the induction of MS-like disease and CNS pathology. Ex vivo functional characteristics of MOG34-56 specific T cells are specific cytolysis of peptide pulsed target cells and high IL-17A production. To indentify possible functions in this new model of T helper 1 cells, which play a central pathogenic role in MS models induced with complete Freund’s adjuvant, we tested the effect of human interferon-γ (IFNγ) administration during disease initiation of the disease (day 0–25) and around the time of disease expression (psd 56–81). The results show a clear modulatory effect of early IFNγ treatment on humoral and cellular autoimmune parameters, but no generalized mitigating effect on the disease course. These results argue against a prominent pathogenic role of T helper 1 cells in this new marmoset EAE model