Roots of the derivative of the Riemann zeta function and of characteristic polynomials

We investigate the horizontal distribution of zeros of the derivative of the Riemann zeta function and compare this to the radial distribution of zeros of the derivative of the characteristic polynomial of a random unitary matrix. Both cases show a surprising bimodal distribution which has yet to be explained. We show by example that the bimodality is a general phenomenon. For the unitary matrix case we prove a conjecture of Mezzadri concerning the leading order behavior, and we show that the same follows from the random matrix conjectures for the zeros of the zeta function.Comment: 24 pages, 6 figure

Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome

OBJECTIVE: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. METHODS: In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). RESULTS: Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients. CONCLUSIONS: Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved

Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome

Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and -62.3 (1.8)% in the ITT and MPP populations, respectively. In the absence of a placebo group, significance of the sustained improvements could not be evaluated directly. However, to provide context for interpretation of results, comparisons were performed with untreated patients from a Morquio A natural history study. In contrast to the results of the extension study, the untreated patients experienced constant uKS levels and a gradual decline in endurance test results over a similar period of time. Differences from the untreated natural history study patients were significant for 6MWT, 3MSCT, and uKS outcomes for the cohort of patients receiving optimal dosing throughout the study and for all cohorts pooled together, for both ITT and MPP populations (P<0.05). Safety findings were consistent with those of the initial 24-week study, with no new safety signals identified

Relationship between Vitamin D, Parathyroid Hormone, and Bone Mineral Density in Elderly Koreans

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome

Validating the Time and Change test to screen for dementia in elderly Koreans

BACKGROUND: We assessed the applicability of the T&C test as an accurate and convenient means to screen for dementia in primary care and community settings. METHODS: The study group comprised 59 patients and 405 community participants, all of who were aged 65 years and over. The time component of the T&C test evaluated the ability of a subject to comprehend clock hands that indicated a time of 11:10, while the change component of the T&C test evaluated the ability of a subject to make 1,000 Won from a group of coins with smaller denominations (one 500, seven 100, and seven 50 Won coins). RESULTS: The T&C test had a sensitivity and specificity of 73.0 and 90.9%, respectively, and positive and negative predictive values of 93.1, and 66.7%, respectively. The test-retest and interobserver agreement rates were both 95% (κ = 0.91) (time interval, 24 hours). The association between the T&C test and K-MMSE test was modest, while significant (r = 0.422, p < 0.001). The T&C test scores were not influenced by educational status. CONCLUSIONS: We conclude that the T&C test is useful as supplemental testing of important domains (e.g., calculation, conceptualization, visuospatial) to traditional measures such as the MMSE. However, because T&C test is simple, rapid, and easy to use, it can be applied conveniently to elderly subjects by non-specialist personnel who receive training

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Korean Version of Mini Mental Status Examination for Dementia Screening and Its' Short Form

Objective We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its short form (SMMSE-DS). Methods We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its age- and education-specific optimal cutoff scores for dementia. Results The internal consistency obtained by Cronbach`s coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects. Conclusion The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels. Psychiatry Investig 2010;7:102-108This study was supported by a research grant from the Ministry of Health and Welfare, Korea (Grant NO. 08-2009-014).Han C, 2008, ARCH GERONTOL GERIAT, V47, P302, DOI 10.1016/j.archger.2007.08.012PARK JH, 2007, PSYCHIAT INVEST, V4, P84Kim KW, 2005, DEMENT GERIATR COGN, V19, P324, DOI 10.1159/000084558JHOO JH, 2005, J KOREAN NEUROPSYCHI, V44, P98KIM HS, 2005, HYEONDAE GUGEO SAYON, V2Boustani M, 2003, ANN INTERN MED, V138, P927KANG Y, 2003, NEUROPSYCHOLOGICAL SLee JH, 2002, J GERONTOL B-PSYCHOL, V57, pP47LEE DY, 2002, J KOREAN NEUROPSYCHI, V41, P508PARK J, 1999, J KOREAN NEUROPSYCHI, V38, P173Malloy PF, 1997, J NEUROPSYCH CLIN N, V9, P189KANG Y, 1997, J KOREAN NEUROL ASS, V15, P300WOO JL, 1996, J KOREAN NEUROPSYCHI, V35, P122LINN RT, 1995, ARCH NEUROL-CHICAGO, V52, P485MASUR DM, 1994, NEUROLOGY, V44, P1427*AM PSYCH ASS, 1994, DIAGN STAT MAN MENTIMAI Y, 1994, J HONG KONG COLL PSY, V4, P20MORRIS JC, 1993, NEUROLOGY, V43, P2412CRUM RM, 1993, JAMA-J AM MED ASSOC, V269, P2386TOMBAUGH TN, 1992, J AM GERIATR SOC, V40, P922FEHER EP, 1992, ARCH NEUROL-CHICAGO, V49, P87HODGES JR, 1990, J NEUROL NEUROSUR PS, V53, P1089GALASKO D, 1990, ARCH NEUROL-CHICAGO, V47, P49OCONNOR DW, 1989, PSYCHOL MED, V19, P771PARK JH, 1989, J KOREAN NEUROPSYCHI, V28, P508OCONNOR DW, 1989, J PSYCHIAT RES, V23, P87HANLEY JA, 1983, RADIOLOGY, V148, P839HUGHES CP, 1982, BRIT J PSYCHIAT, V140, P566ANTHONY JC, 1982, PSYCHOL MED, V12, P397FOLSTEIN MF, 1975, J PSYCHIATR RES, V12, P198