Elevated cerebral spinal fluid biomarkers in children with mucopolysaccharidosis I-H.

Mucopolysaccharidosis (MPS) type-IH is a lysosomal storage disease that results from mutations in the IDUA gene causing the accumulation of glycosaminoglycans (GAGs). Historically, children with the severe phenotype, MPS-IH (Hurler syndrome) develop progressive neurodegeneration with death in the first decade due to cardio-pulmonary complications. New data suggest that inflammation may play a role in MPS pathophysiology. To date there is almost no information on the pathophysiologic changes within the cerebral spinal fluid (CSF) of these patients. We evaluated the CSF of 25 consecutive patients with MPS-IH. While CSF glucose and total protein were within the normal range, we found a significantly mean elevated CSF opening pressure at 24 cm H2O (range 14-37 cm H2O). We observed a 3-fold elevation in CSF heparan sulfate and a 3-8 fold increase in MPS-IH specific non-reducing ends, I0S0 and I0S6. Cytokine analyses in CSF of children with MPS-IH showed significantly elevated inflammatory markers including: MCP-1 SDF-1a, IL-Ra, MIP-1b, IL-8, and VEGF in comparison to unaffected children. This is the largest report of CSF characteristics in children with MPS-IH. Identification of key biomarkers may provide further insight into the inflammatory-mediated mechanisms related to MPS diseases and perhaps lead to improved targeted therapies

mlirSynth: Automatic, Retargetable Program Raising in Multi-Level IR using Program Synthesis

MLIR is an emerging compiler infrastructure for modern hardware, but existing programs cannot take advantage of MLIR's high-performance compilation if they are described in lower-level general purpose languages. Consequently, to avoid programs needing to be rewritten manually, this has led to efforts to automatically raise lower-level to higher-level dialects in MLIR. However, current methods rely on manually-defined raising rules, which limit their applicability and make them challenging to maintain as MLIR dialects evolve. We present mlirSynth -- a novel approach which translates programs from lower-level MLIR dialects to high-level ones without manually defined rules. Instead, it uses available dialect definitions to construct a program space and searches it effectively using type constraints and equivalences. We demonstrate its effectiveness \revi{by raising C programs} to two distinct high-level MLIR dialects, which enables us to use existing high-level dialect specific compilation flows. On Polybench, we show a greater coverage than previous approaches, resulting in geomean speedups of 2.5x (Intel) and 3.4x (AMD) over state-of-the-art compilation flows for the C programming language. mlirSynth also enables retargetability to domain-specific accelerators, resulting in a geomean speedup of 21.6x on a TPU

mlirSynth: Automatic, Retargetable Program Raising in Multi-Level IR using Program Synthesis

MLIR is an emerging compiler infrastructure for modern hardware, but existing programs cannot take advantage of MLIR’s high-performance compilation if they are described in lower-level general purpose languages. Consequently, to avoid programs needing to be rewritten manually, this has led to efforts to automatically raise lower-level to higher-level dialects in MLIR. However, current methods rely on manually-defined raising rules, which limit their applicability and make them challenging to maintain as MLIR dialects evolve. We present mlirSynth – a novel approach which translates programs from lower-level MLIR dialects to high-level ones without manually defined rules. Instead, it uses available dialect definitions to construct a program space and searches it effectively using type constraints and equivalences. We demonstrate its effectiveness by raising C programs to two distinct high-level MLIR dialects, which enables us to use existing high-level dialect specific compilation flows. On Polybench, we show a greater coverage than previous approaches, resulting in geomean speedups of 2.5x (Intel) and 3.4x (AMD) over state-of-the-art compilation flows. mlirSynth also enables retargetability to domain-specific accelerators, resulting in a geomean speedup of 21.6x on a TPU

The impact of changes in Clinical Microbiology Laboratory location and ownership on the practice of Infectious Diseases

The number of onsite clinical microbiology laboratories in hospitals is decreasing, likely related to the business model for laboratory consolidation and labor shortages, and this impacts a variety of clinical practices including banking isolates for clinical or epidemiologic purposes. To determine the impact of these trends, infectious disease (ID) physicians were surveyed regarding their perceptions of offsite services. Clinical microbiology practices for retention of clinical isolates for future use were also determined. Surveys were sent to members of the Infectious Diseases Society of America\u27s (IDSA) Emerging Infections Network (EIN). The EIN is a sentinel network of ID physicians who care for adult and/or pediatric patients in North America and who are members of IDSA. The response rate was 763 (45%) of 1,680 potential respondents. Five hundred forty (81%) respondents reported interacting with the clinical microbiology laboratory. Eighty-six percent of respondents thought an onsite laboratory very important for timely diagnostic reporting and ongoing communication with the clinical microbiologist. Thirty-five percent practiced in institutions where the core microbiology laboratory has been moved offsite, and an additional 7% (N=38) reported that movement of core laboratory functions offsite was being considered. The respondents reported that only 24% of laboratories banked all isolates with the majority saving isolates for less than 30 days. Based on these results, the trend towards centralized core laboratories negatively impacts the practice of ID physicians, potentially delays effective implementation of prompt and targeted care for patients with serious infections, and similarly adversely impacts infection control epidemiologic investigations

Correlating Pedestrian Flows and Search Engine Queries

An important challenge for ubiquitous computing is the development of techniques that can characterize a location vis-a-vis the richness and diversity of urban settings. In this paper we report our work on correlating urban pedestrian flows with Google search queries. Using longitudinal data we show pedestrian flows at particular locations can be correlated with the frequency of Google search terms that are semantically relevant to those locations. Our approach can identify relevant content, media, and advertisements for particular locations.Comment: 4 pages, 1 figure, 1 tabl

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome

Perceptions and behaviours of infectious diseases physicians when managing urinary tract infections due to MDR organisms

Objectives The objective of this study was to attain a better understanding of infectious diseases (ID) physicians' experience with MDR organism (MDRO) urinary tract infections (UTIs) by means of a survey on disease perception, diagnostic management and treatment preferences. Methods A nine-question survey was developed and distributed to members of the North American Emerging Infections Network (EIN) in September 2013. Results Seven hundred and fourteen out of 1461 EIN members responded to the survey (49%). The responses of 603 responders were studied. Most providers perceived an increase in the incidence of MDRO UTIs over the past 3 years (75% of adult ID responders and 63% of paediatric ID responders). One hundred and thirty-four (22%) responders prefer intravenous over oral administration of antimicrobials when both are available, 171 (28%) prefer longer durations of therapy when comparing an MDRO with a susceptible isolate of the same species and 142 (24%) order a repeat urine culture as ‘proof of cure' after treating an MDRO UTI. Nevertheless, 530 (88%) responders perceived MDRO UTIs to be of similar severity as non-MDRO UTIs. Fifty-five percent of providers prescribed fosfomycin for MDRO UTI at least once; the most common prescribing pattern (among a wide spectrum of approaches) was a single dose (16%). Conclusions Future studies on MDRO UTIs should clarify the role of resistance in patient outcomes and the comparative efficacy of different antimicrobials. Of particular interest is fosfomycin, which is unrelated to other antibiotic classes and may take a more prominent role in treating MDRO cystiti