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Background The Centers for Disease Control and Prevention (CDC) funds the Colorectal Cancer Control Program (CRCCP) to increase colorectal cancer (CRC) screening rates in primary care clinics by implementing evidence-based interventions (EBIs). This study examined differences in clinic characteristics and implementation efforts among clinics with differential changes in screening rates over time. Methods CRCCP clinic data collected by the CDC were used. The outcome was the clinic status (highest quartile [Q4] vs lowest quartile [Q1]), which was based on the absolute screening rate change between the first and second program years. Five clinic characteristic variables and 12 clinic-level CRCCP variables (eg, EBIs) were assessed in bivariable analyses, and logistic regression was used to determine significant predictors of the outcome. Results Each group included 78 clinics (N = 156). Clinics with a Q4 status saw a 14.9 percentage point increase in the screening rate, whereas clinics with a Q1 status experienced a 9.1 percentage point decline. Q4s were more likely than Q1s to have a CRC champion, implement 4 EBIs versus fewer EBIs, implement at least 1 new EBI, and increase the number of implemented EBIs. The adjusted odds of Q4 status were 5.3 times greater (95% confidence interval [CI], 1.9-14.9) if a clinic implemented an additional EBI. The adjusted odds of Q4 status increased to 7.1 (95% CI, 2.2-23.1) if a clinic implemented 2 to 4 additional EBIs. Conclusions Implementing new EBIs or enhancing existing ones improves CRC screening rates. Additionally, clinics with lower screening rates had greater rate increases and may have benefited more from the CRCCP.

This study compares a longitudinal population-based sample of spouses bereaved by suicide and those bereaved by other sudden deaths to determine if suicide-bereaved spouses (SBS) experience greater rates of physician-diagnosed mental disorders.First, married individuals whose spouse died by suicide, sudden natural death (SND) and unintentional injury (UI) were compared to non-bereaved matched cohorts to determine if there were differences in mental disorder rates between bereavement groups and non-bereaved matches. Second, SBS (n = 365), spouses bereaved by SND (n = 1000), and spouses bereaved by UI (n = 270), were compared using inverse probability treatment weighting and generalized estimating equations to calculate relative rates of mental disorders 5 years before/after death.All bereaved cohorts had higher rates of mental disorders compared to non-bereaved cohorts. SBS had the greatest rate of depression post-bereavement (50·96%), followed by UI (38·52%) and SND (33·70%) spouses. When comparing bereavement cohorts, a significant group-by-time interaction (P = 0·047) revealed the rate change for depression was significantly different between suicide and UI-bereaved spouses, with SBS having higher rates of depression before bereavement. SBS had increased rates of any mental disorder both pre (ARR = 1·35, 95% CI = 1·03-1·18, P·05) and post spousal death (ARR = 1·24, 95% CI = 1·03-1·45, P·05) when compared to UI spouses signifying pre-existing mental disorders. Post-bereavement, SBS had greater rates of depression only when compared to SND-bereaved spouses (ARR = 1·31, 95% CI = 1·10-1·55, P·01).SBS have the greatest rates of depression and any mental disorder before the death of their spouse, suggesting suicide bereavement may be unique. Sudden spousal bereavement is a vulnerable time for mental disorders.

Objectives Methodological concerns relating to acute-to-chronic workload ratios (ACWR) have been raised. This study aimed to assess the relationship between an alternative predictor variable named ‘differential load’, representing the smoothed week-to-week rate change in load, and injury risk in first class county cricket (FCCC) fast bowlers. Design Prospective cohort study. Methods Bowling loads and injuries were recorded for 49 professional male fast bowlers from six FCCC teams. A range of differential loads and ACWRs were calculated and subjected to a variable selection procedure. Results Exponentially-weighted 7-day differential load, 9:21-day ACWR, 42-day chronic load, and 9-day acute load were the best-fitting predictor variables in their respective categories. From these, a generalized linear mixed-effects model combining 7-day differential load, 42-day chronic load, and 9-day acute load provided the best model fit. A two-standard deviation (2SD) increase in 7-day differential load (22 overs) was associated with a substantial increase in injury risk (risk ratio [RR] = 2.47, 90% CI: 1.27–4.80, most likely harmful), and a 2SD increase in 42-day chronic load (17.5 overs/week) was associated with a most likely harmful increase in injury risk (RR = 6.77, 90% CI: 2.15–21.33). For 9-day acute load, very low values (≤1 over/week) were associated with a most likely higher risk of injury versus moderate (17.5 overs/week; RR: 15.50, 90% CI: 6.19–38.79) and very high 9-day acute loads (45.5 overs/week; RR: 133.33, 90% CI: 25.26–703.81). Conclusions Differential loads may be used to identify potentially harmful spikes in load, whilst mitigating methodological issues associated with ACWRs.

Marshallese and Latino communities in Benton and Washington counties, Arkansas, were disproportionately affected by COVID-19. We evaluated the effectiveness of a comprehensive community-based intervention to reduce COVID-19 disparities in these communities. We examined all laboratory-confirmed COVID-19 cases in the 2 counties reported from April 6, 2020, through December 28, 2020. A 2-sample serial t test for rate change was used to evaluate changes in case rates before and after implementation of the intervention. After implementation, the proportions of cases among Marshallese and Latino residents declined substantially and began to align more closely with the proportions of these 2 populations in the 2 counties. Infection rates remained lower throughout the evaluation period, and weekly incidence also approximated Marshallese and Latino population proportions. Leveraging community partnerships and tailoring activities to specific communities can successfully reduce disparities in incidence among populations at high-risk for COVID-19 .

Background The Chinese population has aged significantly in the last few decades. Comprehensive health losses including both fatal and non-fatal health outcomes associated with ageing in China have not been detailed. Methods Based on freely accessible disability adjusted life years (DALYs) estimated by the Global Burden of Diseases (GBD) 2017, we adopted a robust decomposition method that ascribes changes in DALYs in any given country across two time points to changes resulting from three sources: population size, age structure, and age-specific DALYs rate per 100,000 population. Using the method, we calculated DALYs associated with population ageing in China from 1990 to 2017 and examined the counteraction between the effects of DALYs rate change and population ageing. This method extends previous work through attributing the change in DALYs to the three sources. Results Population ageing was associated with 92.8 million DALYs between 1990 and 2017 in China, of which 65.8% (61.1 million) were years of life lost (YLLs). Males had comparatively more DALYs associated with population ageing than females in the study period. The five leading causes of DALYs associated with population ageing between 1990 and 2017 were stroke (23.6 million), chronic obstructive pulmonary disease (COPD) (18.3 million), ischemic heart disease (13.0 million), tracheal, bronchus, and lung cancer (6.1 million) and liver cancer (5.0 million). Between 1990 and 2017, changes in DALYs associated with age-specific DALY rate reductions far exceeded those related to population ageing (− 196.2 million versus 92.8 million); 57.5% (− 112.8 million) of DALYs were caused by decreases in rates attributed to 84 modifiable risk factors. Conclusion Population ageing was associated with growing health loss in China from 1990 to 2017. Despite the recent progress in alleviating health loss associated with population ageing, the government should encourage scientific research on effective and affordable prevention and control strategies and should consider investment in resources to implement strategies nationwide to address the future challenge of population ageing.

BACKGROUND AND AIMS The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P

To review the evolution of female continence surgical practice in Australia over the last 20 years and observe whether vaginal mesh controversies impacted these trends. From January 2000 to December 2019, medicare benefit schedule codes for female continence procedures were identified and extracted for: mesh sling, fascial sling, bulking agent, female urethral prosthesis, colposuspension, and removal of sling. Population-adjusted incidences per 100,000 persons were calculated using publicly available demographic data. Three discrete phases were defined over the study time frame for analysis: 2000–2006; 2006–2017, and 2017–2019. Interrupted time-series analyses were conducted to assess for impact on incidence at 2006 and 2017. There were 119,832 continence procedures performed in Australia from 2000 to 2019, with the mid-urethral sling (MUS) the most common (72%). The majority of mesh (n = 63,668, 73%) and fascial sling (n = 1864, 70%) procedures were in women aged

Background The rapid increase of bacterial antibiotic resistance could soon render our most effective method to address infections obsolete. Factors influencing pathogen resistance prevalence in human populations remain poorly described, though temperature is known to contribute to mechanisms of spread. Aim To quantify the role of temperature, spatially and temporally, as a mechanistic modulator of transmission of antibiotic resistant microbes. Methods An ecologic analysis was performed on country-level antibiotic resistance prevalence in three common bacterial pathogens across 28 European countries, collectively representing over 4 million tested isolates. Associations of minimum temperature and other predictors with change in antibiotic resistance rates over 17 years (2000–2016) were evaluated with multivariable models. The effects of predictors on the antibiotic resistance rate change across geographies were quantified. Results During 2000–2016, for Escherichia coli and Klebsiella pneumoniae, European countries with 10°C warmer ambient minimum temperatures compared to others, experienced more rapid resistance increases across all antibiotic classes. Increases ranged between 0.33%/year (95% CI: 0.2 to 0.5) and 1.2%/year (95% CI: 0.4 to 1.9), even after accounting for recognised resistance drivers including antibiotic consumption and population density. For Staphylococcus aureus a decreasing relationship of −0.4%/year (95% CI: −0.7 to 0.0) was found for meticillin resistance, reflecting widespread declines in meticillin-resistant S. aureus across Europe over the study period. Conclusion We found evidence of a long-term effect of ambient minimum temperature on antibiotic resistance rate increases in Europe. Ambient temperature might considerably influence antibiotic resistance growth rates, and explain geographic differences observed in cross-sectional studies. Rising temperatures globally may hasten resistance spread, complicating mitigation efforts.

Background and Purpose— Data on recent time trends in stroke mortality by subtypes and regions are lacking for Germany. We investigated sex- and age-standardized trends in stroke mortality in Germany for different stroke subtypes from 1998 to 2015 and assessed potential regional variations between the former Eastern and former Western part of Germany. Methods— Mortality and population data from the German Federal Statistical Office were used to calculate sex- and age-standardized mortality rates for hemorrhagic stroke, ischemic stroke, and total strokes from 1998 to 2015 for all age groups. Joinpoint regression was used to examine trends and its changes. Estimations were stratified for Eastern and Western part of Germany. Results— From 1998 to 2015, age-standardized total stroke mortality decreased by >50% in men (from 78.0 to 34.1 per 100 000) and women (from 62.1 to 28.4 women per 100 000). The decrease was more pronounced for ischemic stroke mortality (rate change: men, −66%; women, −63%) than for hemorrhagic stroke mortality (men, −40%; women, −31%). Total and ischemic stroke mortality declined more in Eastern than in Western part of Germany. From 1998 to 2015, there were no differences in the decline between the regions in hemorrhagic stroke mortality. Total stroke mortality was higher in Eastern compared with Western part of Germany throughout the study period. Differences in subtype- and sex-specific mortality between the regions decreased from 1998 to 2015. Conclusions— Between 1998 and 2015, stroke mortality declined substantially in Germany with differing time trends in stroke subtypes between sexes and regions. Differences in stroke mortality rates between East and West Germany are negligible 24 years after the German reunification.

Objective: To examine the longitudinal trajectory of daytime dysfunction (DD) and its relationship with fatigue by depression status in university students.Participants: 243 students completed online surveys from September- December 2016.Methods: Surveys were conducted at three time points over a semester period: the beginning of the semester, the end of mid-term and the end of the semester.Results: Results indicated that the DD significantly increased in all students over the semester. Students with depression showed a higher initial level of DD and faster rate of change compared to those without depression. A faster rate of change of DD predicted a higher level of end-semester fatigue.Conclusions: Depression is related to a higher initial level of DD and its faster rate change which in turn, predicted end-semester fatigue, identifying one of the possible pathways through which depression impacts the functioning and health of affected students.

Catheter-associated urinary tract infections account for 40% of healthcare-acquired infections. This study explored the addition of cloud-based software technology to an established nursing quality improvement program to reduce catheter-associated urinary tract infections. Unit-based nurse champions evaluated peers' evidence-based catheter-associated urinary tract infection prevention practices using manual, paper-based feedback. That process achieved reduced rates of catheter-associated urinary tract infection over 18 months. However, it was resource intensive. Cloud-based software technology was introduced to replace the paper. Nurse champions' satisfaction, catheter-associated urinary tract infection and indwelling urinary catheter utilization, and prevention practices were compared before and after the technology intervention. Compliance with the provision of a chlorhexidine bath demonstrated improvement (P = .003), while other practice measures did not significantly change. The indwelling urinary catheter utilization ratio was lower (P = .01), yet the intervention yielded no change in catheter-associated urinary tract infection rates. The short time interval of the intervention was potentially a contributing factor in no significant rate change. Nurse champions (N = 14) were more satisfied with the cloud-based technology (P = .004), the clarity of improvement targets (P = .004), and the speed of sharing data (P = .001). Their time to share data decreased from 4 days or more to 1 hour or less. Nurse champions readily adopted the cloud-based technology. These findings suggest additional research on technology innovations for nursing quality improvement is needed.

BACKGROUND AND OBJECTIVE: Diabetic blindness occurs most often among working-age people. Panretinal photocoagulation (PRP) can prevent this outcome. Administrative data examined changes in PRP incidence rates. PATIENTS AND METHODS: Anonymous data from the “claims submitted” files of an insurer with nationwide representation was used. This health insurance was a job benefit, and the sample included 6,085,750 U.S. employees and their dependents. Those who received PRP for diabetic retinopathy were compared to all others with diabetes mellitus. Although some enrollees had more than one PRP procedure, each procedure was considered a unique event. The rate change was evaluated by chi-square tests with post hoc tests for pair-wise comparisons. RESULTS: A total of 14,856 PRP procedures were performed. An incidence rate reduction from 0.95% to 0.67% (chi-square = 243.6818, P < .0001) was found within the study interval. CONCLUSION: The incidence of PRP was reduced in this sample of U.S. workers and their dependents.

This article examines alcohol-impaired collision metrics around nine sobriety checkpoint locations in Indianapolis, Indiana, before and after implementation of 22 checkpoints, using a pre/post examination, a pre/post nonequivalent comparison group analysis, and an interrupted time series approach. Traffic safety officials used geographical information system (GIS) analysis to help select checkpoint locations amid high alcohol-related collision clusters, then analyzed possible checkpoint impacts. A post hoc analysis examined counts and rates of impaired collisions before and after checkpoint dates within the 2-mile radius zones around each checkpoint site and compared pre-to-post differences to two similar time-matched control areas without checkpoints. As a group, checkpoint zones showed significant though minor declines in pre-to-post collision counts, and no impairment rate change. Considered together, non-downtown checkpoint zones had more favorable impairment rates than comparison areas. After controlling for collision volume, monthly trend, and locational effects, the interrupted time series analysis found that for all checkpoints the count of impaired collisions in post-checkpoint periods was about 19% less than pre-checkpoint counts.

Descriptive data are presented on the natural occurrence of stereotyped body rocking in three institutionalised, mentally retarded children. Both ward and test situation observations suggest that there is spontaneous fluctuation in rate of body rocking. These findings raise a serious methodological problem pertinent to the evaluation of experimental data on stereotyped behaviour: rate change attributed to experimental manipulation may in fact only be an instance of spontaneous fluctuation.

Functional constraints on proteins limit their evolutionary rates at specific sites. These constraints allow for the interpretation of conserved residues and sites with a rate change as those most likely underlying the functional similarities and differences among protein subfamilies, respectively. This study describes new likelihood-ratio tests (LRTs) that complement existing ones for the identification of both conserved and rate change sites. These identifications are validated by the recovery of residues that are known from existing biochemical and structural information to be critical for the functional similarities and differences among carbonic anhydrases (CAs). In combination with this other information, these LRTs also support a unique antioxidant defense role for the puzzling CA III. As illustrated by the CAs, these LRTs, in combination with other biological evidence, offer a powerful and cost-effective approach for testing hypotheses, making predictions, and designing experiments in protein functional studies.

BACKGROUND The incidence of non-Hodgkin lymphoma (NHL) has been rising in many regions and populations during the last few decades. Data from the Surveillance, Epidemiology, and End Results (SEER) Program show that age-adjusted rates of NHL increased through the 1980s but leveled off in the 1990s. METHODS To determine whether the incidence of NHL stabilized in all population subgroups, particularly in age-defined groups with distinctive risks of NHL, the authors investigated trends in NHL incidence among persons aged 0–14 years, 15–24 years, 25–34 years, 35–44 years, 45–54 years, 55–64 years, 65–74 years, and > 75 years by gender and race using 1973–1998 data from the SEER Program, which covered approximately 10% of the U.S. population. Joinpoint regression was used to assess changes in trends across the period. RESULTS NHL incidence trends changed significantly among males aged 25–54 years, in whom rates began to decrease (6–16% per year) in the middle to late 1990s, as well as among most whites aged ≥ 55 years, in whom rate increases slowed from 3–4% to 1–2% per year in the late 1980s. Incidence trends were steady in other groups, with uniform increases among whites aged 15–24 years (2–3% per year), women aged 25–54 years (1–6% per year), and blacks aged ≥ 55 years (2–4% per year). Although recent age specific incidence rates were generally higher in males compared with females and in whites compared with blacks, among males aged 25–54 years, rates were significantly higher in black males compared with white males. CONCLUSIONS There have been changes in the demographic groups impacted by NHL. The trends for human immunodeficiency virus probably are related to recent decreases in NHL incidence among males aged 25–54 years. The rate change in the older white population is unexplained but represents both an alleviation of the burden of NHL in this population and a potential opportunity to generate hypotheses regarding risk factors for the development of NHL. Cancer 2002;94:2015–23. © 2002 American Cancer Society. DOI 10.1002/cncr.10403

This study sought to characterize the relationship among voluntary rate modification, vocal tract acoustic output, and perceptual impressions of speech for individuals with idiopathic Parkinson disease (PD). Healthy control speakers were studied for comparison purposes. Four research questions were addressed: (1) How is rate modification evidenced in acoustic measures of segmental and global timing? (2) What is the impact of rate modification on measures of acoustic working space for select vowels and consonants? (3) What is the impact of rate modification on perceptual impressions of severity? (4) Are rate-induced changes in measures of acoustic working space related to perceptual impressions of severity? Speakers read the Farm Passage at habitual, slow, and fast rates. The vowels /i/, /æ/, /u/, and /a/ and the fricatives /s/ and /∫/ were of interest. Acoustic measures included articulatory rate, segment durations, vowel formant frequencies, and first moment coefficients. Measures of acoustic working space for vowels and fricatives also were derived. The results indicated that temporal acoustic measures changed in the expected direction across rate conditions, with a tendency toward slightly faster rates for the PD group. In addition, the relative rate change for the Fast and Slow conditions compared to the Habitual condition was similar across groups. Rate did not strongly affect measures of acoustic working space for the PD group as a whole, but there was a tendency for slower rates to be associated with larger measures of acoustic working space. Finally, there was not a strong relationship between perceived severity and measures of acoustic working space across the rate continuum for either group. Rather, the relationship between perceived severity and measures of acoustic working space was such that the PD group exhibited smaller measures of acoustic working space and more severe perceptual estimates than the control speakers, irrespective of rate condition.

Oxygen consumption (VO 2 ) on-kinetics describes the rate change in oxygen uptake at the initiation of exercise. Several mathematical and graphical methods are used to assess VO 2 on-kinetics during constant-load or progressive exercise. VO 2 on-kinetics is prolonged in patients with heart failure (HF) compared with individuals who have normal cardiopulmonary function. Cardiac function has been implicated as one of the controlling mechanism for this observation. The contribution that pulmonary, vascular, and skeletal muscle function makes to delayed VO 2 on-kinetics in HF has yet to be determined. VO 2 on-kinetics also appears to have clinical value in HF, although evidence supporting this claim is limited. Questions about the controlling mechanism(s) and practical application of VO 2 on-kinetics in HF therefore remain unanswered. This report provides an overview of VO 2 on-kinetics assessment techniques, reviews research pertaining to the HF population, and provides direction for future investigations.

BACKGROUND The aim of this study was to examine developmental trends in rate change detection of auditory rhythmic signals (repetitive sinusoidally frequency modulated tones). METHODS Two groups of children (9-10 years old and 11-12 years old) and one group of young adults performed a rate change detection (RCD) task using three types of stimuli. The rate of stimulus modulation was either constant (CR), raised by 1 Hz in the middle of the stimulus (RR1) or raised by 2 Hz in the middle of the stimulus (RR2). RESULTS Performance on the RCD task significantly improved with age. Also, the different stimuli showed different developmental trajectories. When the RR2 stimulus was used, results showed adult-like performance by the age of 10 years but when the RR1 stimulus was used performance continued to improve beyond 12 years of age. CONCLUSIONS Rate change detection of repetitive sinusoidally frequency modulated tones show protracted development beyond the age of 12 years. Given evidence for abnormal processing of auditory rhythmic signals in neurodevelopmental conditions, such as dyslexia, the present methodology might help delineate the nature of these conditions.

We investigated the changes in step temporal parameters and spring-mass behaviour during the running phase of a major international triathlon competition. 73 elite triathletes were followed during the 2011 World Championships Grand Final. The running speed, ground contact and flight times were assessed over a 30 m flat section at the beginning of the 4 running laps and towards the finish line, by using a high-frequency camera (300 Hz). The leg and vertical stiffness, and vertical displacement of the mass centre were calculated from step temporal characteristics. A concomitant decrease in running speed, vertical stiffness and leg stiffness was reported during the 4 running laps, except towards the finish line, where these parameters increased. Running biomechanics was not affected between the beginning and the end of the 10 km run, when triathletes were compared for the same running speed (1.68±0.16 m vs. 1.70±0.17 m for step length, 3.18±0.11 Hz vs. 3.16±0.15 Hz for step rate, 12.87±3.14 kN.m − 1 vs.12.76±3.05 kN.m − 1 for Kleg, 31.18±4.71 kN.m − 1 vs.30.74±3.88 kN.m − 1 for Kvert, at lap1 and finish, respectively). Multiple regression models revealed that both step rate change and step length change were correlated with running speed change and that the standardized partial regression coefficient was higher for step length change than for step rate. Independent of the cofounding effect of speed and despite the neuromuscular fatigue previously shown after long-duration events, the lower limb mechanical stiffness and the overall spring-mass regulation were not altered over the 10 km triathlon run in elite competitors. This study showed also that step length explained, to a greater extent than step frequency, the running speed variance in elite triathletes.

The Mayak Production Association released large amounts of (90)Sr into the Techa River (Southern Urals, Russia) with peak amounts in 1950-1951. Techa Riverside residents ingested an average of about 3,000 kBq of (90)Sr. The (90)Sr-body burden of approximately 15,000 individuals has been measured in the Urals Research Center for Radiation Medicine in 1974-1997 with use of a special whole-body counter (WBC). Strontium-90 had mainly deposited in the cortical part of the skeleton by 25 years following intake, and (90)Sr elimination occurs as a result of cortical bone resorption. The effect of (90)Sr-radiation exposure on the rate of cortical bone resorption was studied. Data on 2,022 WBC measurements were selected for 207 adult persons, who were measured three or more times before they were 50-55 years old. The individual-resorption rates were calculated with the rate of strontium recirculation evaluated as 0.0018 year(-1). Individual absorbed doses in red bone marrow (RBM) and bone surface (BS) were also calculated. Statistically significant negative relationships of cortical bone resorption rate were discovered related to (90)Sr-body burden and dose absorbed in the RBM or the BS. The response appears to have a threshold of about 1.5-Gy RBM dose. The radiation-induced decrease in bone resorption rate may not be significant in terms of health. However, a decrease in bone remodeling rate can be among several causes of an increased level of degenerative dystrophic bone pathology in exposed persons.

Purpose The performance of a weight-based dosing protocol for unfractionated heparin (UFH) infusions using antifactor Xa monitoring was evaluated. Methods The first 50 patients to receive a UFH infusion per the new protocol for over 24 hours, regardless of indication, were included in the analysis. All patients received a bolus dose of 26 units/kg, followed by an i.v. infusion of 15 units/kg/ hr based on actual body weight, with no maximum dosage. Antifactor Xa levels were measured every 6 hours after infusion initiation and after every rate change until stable, defined as two consecutive results within the target range of 0.3–0.7 unit/mL, and every 24 hours thereafter. If a level was outside of the target range, the infusion rate was adjusted. Primary outcomes measured included the percentage of patients with a target level at the first test (obtained 6 hours after the start of therapy) and within the first 24 hours. The success of the protocol in obese patients versus nonobese patients was also analyzed. Results Of the 50 patients enrolled, 26 (52%) achieved a target antifactor Xa concentration 6 hours after infusion initiation. Only 4 patients did not have an antifactor Xa concentration in the target range within 24 hours. Of the 17 patients weighing more than 100 kg, 16 (94%) had a value within the target range within 24 hours. Conclusion A weight-based UFH dosing nomogram using antifactor Xa monitoring resulted in a high percentage of patients achieving target antifactor Xa values within the first 24 hours of therapy.

Objective.—To measure the perceived rate of flicker (temporal frequency) observed during visual auras. Background.—The flickering or scintillating quality of aura elements is a commonly described characteristic of visual migraine auras. Hypotheses about the neural mechanisms involved in aura have rarely taken this feature into account, perhaps because of a lack of quantitative data on this aspect of the aura. While a rate of 10 Hertz had been suggested in the literature, estimates have been speculative due to the difficulty of judging temporal frequencies subjectively. Methods.—Eleven participants were given portable devices that contained an adjustable light-emitting diode with which to match the flickering of their auras. Observers were asked to make flicker matches at two time points so that rate change during aura progression could be analyzed. Results.—Data were obtained for 36 aura episodes. The mean rate of flicker across individuals was 17.8 Hertz. Rates varied widely between individuals, but were more consistent across multiple episodes in the same observer. Rate of flicker did not appear to relate to aura side or type, or to individual characteristics such as migraine history. When episodes were analyzed for change in flicker rate over time, patterns of increase (n = 7), decrease (n = 4), and no change (n = 22) were all observed. Conclusions.—When measured with an objective task, aura scintillation rates were found to be somewhat higher than previous anecdotal observations had suggested. These data are discussed in the context of two competing hypotheses concerning the neural mechanism underlying the flicker percept during migraine aura.

We examined the effects of stimulus rates on the somatosensory evoked potential (SEP) amplitudes following median nerve stimulation at the wrist in 42 children. We divided these subjects into five groups according to their age (0-6 months, 7-12 months, 1-3 years, 4-6 years and more than 7 years) and measured the peak-to-peak amplitude of every component (N9, P10, N11, P13/14, N18, N20, P23, N30) at stimulus rates of 1.0, 3.5 and 5.5 Hz. From N9 to N18, there was no significant change in amplitude nor latency with stimulus rate change in all groups. The amplitude attenuation was found at the N20 and N30 peaks in the young group (0 months to 3 years) and at P23 in all groups with an increasing stimulus rate. The attenuation rate of P23 amplitude was influenced by the age of subjects, being greater in younger groups and greatest in the youngest group (0-6 months). The differences of amplitude attenuation rate between this group and the rest were statistically significant. The results of this study indicate that the amplitudes of the cortical components of SEP in children are greatly influenced by the stimulus rate. Thus when we discuss the amplitude of cortical waves in childhood, we should also pay attention to the stimulus rates.

Estimates derived from linear models fitted to melanoma death rates at successive time periods for the contiguous states of the US suggest that, allowing for latitude, rates are higher in the coastal than in the interior states. The effect of latitude on melanoma death rates in the white population of the US is decreasing and will shortly be gone. This decrease is slower in the interior states than in the coastal ones. The deceleration of the rate change is most marked in the states with the highest rates, so that latitude may be regarded as a determinant of the initial rate for each state, while the subsequent change in rate is a function of that initial rate. Melanoma death rates appear to be stabilizing at levels that are unaffected by latitude.

Observations of inappropriate rate increase in five patients with minute ventilation rate responsive implanted pacemakers (Telectronics Meta) are reported. Pacing rate increases were observed immediately upon connection of the resting patients to two brands of widely used cardiac monitors, and one commonly used echocardiograph. In some circumstances, the rate increase remained until monitor disconnection; in others the rate increase was transient, lasting and 20 seconds. A hardware thoracic resistance variation simulator was constructed and connected to one of the pacemakers to test sensitivity to rate modifying interference from external sources. This demonstrated that the sensitivity to interference is dependent upon the frequency of the interfering signal and is highest in the range 10-60 kHz, that peak currents as low as 10 microA can cause maximum rate increase, and that the signals injected into patients by several cardiac monitors, for purposes of lead-off detection or respiratory monitoring, fall into the frequency range at which the pacemaker is most susceptible to interference.

This article reviews the history of Clinical Global Impressions of Change (CGIC) instruments, their use and limitations in clinical trials of Alzheimer's disease, and the development of the National Institute on Aging's Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC). Originally, CGICs were simple and unstructured instruments that asked a clinician to rate change over the duration of a clinical trial. The method, however, failed to consistently detect treatment effects, leading to the development of more structured and subsequently validated approaches, such as the Clinician Interview-Based Impression Scale (CIBI) and the ADCS-CGIC. Both are currently used in clinical trials. The implications and importance of choosing an appropriate global rating are discussed.

We measured the maximum urinary flow rate monthly for 1 year by uroflowmetry in 1,645 patients in a double-blind, placebo-controlled study of finasteride therapy for benign prostatic hyperplasia. Patients were randomized to receive placebo (555) or finasteride (1,090). A total of 23,857 flow measurements was obtained. Because of the presence of artifacts on many uroflow curves, we read the maximum urinary flow rate values manually and compared them to the values provided electronically by the uroflowmeter. On average, the manually read values were 1.5 ml. per second lower than the machine read values. Artifacts causing a difference of 2 ml. per second or more between the 2 methods were found in 20% and of more than 3 ml. per second in 9% of the tracings. The difference between treatment groups in mean maximum urinary flow rate change at the end of the study was the same with both reading methods. However, confidence intervals were 15 to 25% larger for the machine read compared to the manually read values. This larger variability in machine read maximum urinary flow rate has a marked negative impact on the power of statistical tests to assess any given difference in maximum urinary flow rate between treatment groups. Furthermore, it increases sample size requirements by 50% to achieve any given statistical power. We conclude that maximum urinary flow rate artifacts contribute significantly to the variability of maximum urinary flow rate measurement by uroflowmetry. Manual reading of the maximum urinary flow rate eliminates an important fraction of such variability.

Objectives To determine rates of visual field change associated with risk factors for progression in the Canadian Glaucoma Study (abnormal anticardiolipin antibody level, age, female sex, and mean follow-up intraocular pressure [IOP]), and to evaluate the effect of IOP reduction on subsequent rates of visual field change in progressing patients. Methods Two hundred sixteen patients (median age, 65.2 years) were followed up at 4-month intervals with perimetry and were monitored for progression. Patients reaching an end point based on total deviation analysis underwent 20% or greater reduction in IOP. Rates of mean deviation (MD) change were calculated. Results Patients with 0, 1, and 2 end points had a median of 18, 23, and 25 examinations, respectively. The median MD rate in progressing patients prior to the first end point was significantly worse compared with those with no progression (-0.35 and 0.05 dB/y, respectively). An abnormal anticardiolipin antibody level was associated with a significantly worse MD rate compared with a normal anticardiolipin antibody level (-0.57 and -0.03 dB/y, respectively). Increasing age was associated with a worse MD rate, but female sex and mean follow-up IOP were not. After the first end point, the median IOP decreased from 18.0 to 14.8 mm Hg (20% in individual patients), resulting in a significant MD rate change from -0.36 to -0.11 dB/y. Conclusions Patients with abnormal anticardiolipin antibody levels and increasing age had faster visual field change. Modest IOP reduction in progressing patients significantly ameliorated the rate of visual field decline. Trial registration clinicaltrials.gov Identifier: NCT00262626.

Implantable sensors play an important role in physiological cardiac pacing. Sensors can be classified according to the technical methods in which sensing is achieved: the sensing of the evoked ventricular response, intrathoracic impedance and body acceleration forces, and the incorporation of special sensors on pacing electrodes. These sensors differ in their relative merits in terms of speed, proportionality, sensitivity, and specificity of rate response. The efficacy of a sensor can be significantly modified by the algorithm used in relating sensor signal to a pacing rate change. The currently available types of sensors and algorithms are summarized and compared in this review article. The relative merits of these sensors and algorithms form the basis for designing a multisensor pacing system.

One of the key problems of experimental gerontology is that there is usually some degree of uncertainty in the correct interpretation of experimental or observational data. Namely, it is difficult to decide whether the changes in life span, mortality rate or physiological state are due to the changes in biological age of organisms or to other causes. The analysis of mortality curves, suggested here, can reveal relevant information and may also contribute to discussions on the nature of the aging process. Our models are designed to provide a mathematical and system-theoretical basis to this methodology. The conditions of the validity of the models are simple and their relevancy to reality is discussed. Further, the reliability model suggests an explanation of apparent discrepancy between constant relative decline in physiological functions, often observed during aging, and Gompertzian growth of mortality.

Thresholds for detection of frequency modulation were obtained from three chinchillas at seven frequencies between 320 Hz and 12.75 kHz and at three sensation levels (20, 40, 60, dB SL). These were compared with human thresholds at 40 dB SL obtained under the same conditions. Our data show no significant impact of sensation level and confirm Nelson and Kiester 's [J. Acoust. Soc. Am. 64, 114-126 (1978)] report that the chinchilla has much poorer frequency discrimination than man. In an attempt to assess separately the chinchilla's capacity for temporal coding of frequency, thresholds for detection of a change in the modulation rate of amplitude modulated noise were obtained for nine modulation frequencies between 10 and 320 Hz. The chinchillas needed a larger rate change for detection than most humans but the relative difference was less than that found for frequency modulation detection.

The rate of QT adaptation to abrupt changes in pacing rate was studied in seven patients with newly diagnosed complete heart block with a ventricular escape rate of less than 40 beats.min-1. Their median age was 70 (range 36-84) years, and none was taking any cardioactive medication known to affect the QT interval. From a baseline pacing rate of 50 or 110 beats.min-1 the ventricular rate was increased or decreased to a new level. The time taken for the ventricular paced QT interval to complete 90% of the change secondary to the change in rate was found to be 136(16) s (mean(SEM] when the rate was increasing and 189(25) s when the rate was decreasing (p less than 0.01). This time interval was independent of the magnitude of the rate change and the baseline heart rate from which the change occurred. Furthermore, the time course of QT adaptation was found to be exponential and was characterised by a time constant of 49.1(2.2) s when the rate was increasing and 60.4(2.0) s when the rate was decreasing (p less than 0.01). It is concluded that QT measurements in response to a change in pacing rate should take into account the time dependent nature of QT changes.

The present investigation examined the relationship between affect and pulse rate (PR) change for individuals with different sensation-seeking preferences. Based on their scores on the Sensation-Seeking Scale (Zuckerman, Kolin, Price, & Zoob, 1964), high (HSS) and low (LSS) sensation-seekers were assigned randomly to either 40 minutes of feedback or nofeedback in PR. Subjects were instructed either to decrease or to increase PR. Measures of affect were administered after the 40-minute period. The results indicated that while feedback caused subjects to change PR in either direction, HSS subjects were more successful at increasing, while LSS subjects were more successful at decreasing. Moreover, negative affect resulted only when HSS subjects decreased and LSS subjects increased PR. The results are discussed in terms of the importance of considering individual differences in preference for activation in order to clarify the relationship between physiological and affective responses.

In a companion article [L. I. Hellstrom, J. Acoust. Soc. Am. 85, 230-242 (1989)], it was shown that psychophysical pulsation threshold masking patterns (PTPs) for high-pass noise maskers are not a simple transformation of the profile of activity evoked in the auditory nerve by the masker. In this article, PTPs are compared with neural representations in which interactions of masker and probe are considered. It is hypothesized that, at pulsation threshold, some criterion value of rate change occurs when the stimulus switches from masker to probe. The iso-rate probe level, defined for single auditory-nerve fibers, is the probe level at which this rate change is zero. Iso-rate probe levels are lowest when probe frequency equals best frequency (BF) of the fiber. Profiles of iso-rate probe level versus BF (equal to probe frequency) are qualitatively similar to PTPs but differ quantitatively, e.g., in the rate of growth of probe level with masker level (1.2 dB/dB for PTPs, 0.54 dB/dB for iso-rate profiles). Quantitative differences can be further reduced by requiring a positive rate criterion. These results suggest that PTPs are not solely a reflection of the internal representation of the masker, but reflect responses to the probe tone as well.

A new rating instrument, the Glasgow Assessment Schedule (GAS), is described for the evaluation of head injury outcome. The instrument, which has been used in samples of head-injured men, provides for a comprehensive assessment, and can distinguish mildly and severely injured patients and rate change over time. Inter-rater reliability and concurrent validity with a global rating scale has been found to be satisfactory. It is expected that the GAS will mainly be of use in clinical and research settings in which longer-term management is envisaged.

Skeletal myopotentials may inhibit the output of unipolar demand ventricular pacemakers, resulting in protracted episodes of asystole in susceptible patients. The new DDD-mode pacemakers have, in addition to a unipolar ventricular lead, a unipolar atrial lead to enable atrioventricular sequential or atrial synchronous function. During clinical investigation of a new dual-unipolar cardiac pacing system programmed to operate in the DDD mode (Pace-setter AFP models 281 and 283), 6 patients were noted (5 men and 1 woman, aged 22 to 68 years) who manifested paroxysmal acceleration of ventricular pacing rate approaching the maximal tracking rate. Two patients also had abrupt slowing or cessation of ventricular output. With the use of atrial electrographic recordings (obtained with telemetry), the following mechanisms of rate change were found: myopotential tracking, myopotential inhibition, interference-mode asynchronous operation, sudden increases in sinus rate, and pacemaker-mediated reentrant tachycardia. In all patients, reprogramming of the implanted devices, based on telemetered atrial electrography, resulted in disappearance of the arrhythmias and loss of symptoms while maintaining the DDD pacing mode. Thus, several mechanisms of rhythm disturbances are peculiar to dual-chamber cardiac pacing systems that use unipolar electrodes. Endocardial telemetry combined with extensive programming capability offers the best opportunity for proper diagnosis and management of these problems.

We asked the question, if the amount of nutrients given parenterally is progressively increased, does the rate of whole body protein synthesis rate increase correspondingly and how does the protein breakdown rate change? Eight malnourished patients requiring total parenteral nutrition (TPN) were studied. We measured their whole body protein synthesis and breakdown rate four times at intervals of 3 days using 15N glycine as the tracer. The first study was done pre-TPN. The 2nd, 3rd, and 4th studies were done at increasing TPN rates. The rates were TPN 1, 1440 kcal/day and 7.9 g/N/day; TPN 2, 2160 kcal/day and 11.9 g/N/day; TPN 3, 2880 kcal/day and 15.8 g/N/day. The protein synthesis rate initially increased as the amount of TPN was increased, but increasing the rate from TPN-2 to TPN-3 did not result in further increase. Increasing the rate of TPN above a certain level does not lead to a concomitant increase in the protein synthesis rate.

A simple, but relatively accurate, method of interpreting spectrophotometer analyses of liquor amnii using rate of change of optical density with respect to wavelength is described. The method gives a quantitative result that reduces interpretative bias and can be used with either automatic or manual spectrophotometers. It also indicates that, in addition to either optical density (or percent transmittances) as a function of wavelength being provided by automatic spectrophotometers, the rate change of either of these quantities with respect to wavelength could assist spectrophotometric analysis generally.

Microelectrophysiologic studies of canine and human ventricular myocardium demonstrate characteristic changes in the configuration of the transmembrane action potential upon abrupt rate change. Additional studies have shown also that these action potential changes, involving cellular repolarization (phase 2 and phase 3), correlate closely with the magnitude of the concurrent postextrasystolic contractile changes. Further experiments in normal anesthetized dogs demonstrate that the postextrasystolic T wave change relates significantly to the magnitude of the postextrasystolic contractile potentiation. In addition, depression of the contractile state by pentobarbital enhanced the relative magnitude of postextrasystolic contractile change, whereas enhancement of the contractile state by acetylstrophanthidin yielded a lessening of the relative magnitude of postextrasystolic contractile potentiation. However, the associated T wave relation persists, as a result of which the postextrasystolic T wave change is more prominent in the presence of myocardial depression of contractility. It has therefore been suggested that the postextrasystolic T wave change is basically a normal phenomenon correlating with the magnitude of postextrasystolic contractile change. The observed association of the postextrasystolic T wave change with myocardial disease may reflect the relatively greater postextrasystolic contractile change associated with depression of the contractile state. A review of clinical electrocardiograms appears to corroborate this contention, demonstrating that when other variables are excluded exhibition of the postextrasystolic T wave change relates significantly to the closeness of the coupling of the premature complex and the magnitude of the base line T wave.

Because the response and time scales used in plotting cumulative response curves are often poorly selected, ineffective displays often result. The visual cue of a response rate change is the difference, [Formula: see text] between the angles, theta(1) and theta(2), representing the two rates, R(1) and R(2). These variables are related by: [Formula: see text] For a given rate change, the value of theta(1), namely, (M)theta(1), that yields the maximum value of [Formula: see text] namely, [Formula: see text] is given by (M)theta(1)=arc sin [Formula: see text] Ideally, the initial response rate should be represented by the (M)theta(1) appropriate for a given rate change. Because of practical considerations, however, some compromises with the ideal are allowable. Included in the discussion are (a) steps required to select appropriate response and time scales, with examples, and (b) guideposts for evaluating rate changes by means of angular changes.

An experimental study designed to determine the effects of non-contingent and contingent reinforcement of eye contact on the behavior of a 41/2-year-old autistic boy is presented after a brief critical review of pertinent literature. Rate changes in 20 types of behavior comprising a variety of simple responses, contacts, vocalizations, verbalizations or movements under the two reinforcement conditions and during baseline, were recorded and compared. Significant changes were found in the frequency of vocalization, eye contact, and when the child placed his hands over ears. It is suggested that when many types of behavior are examined simultaneously there are some which show as marked a change during non-contingent as during contingent reinforcement. Reinforcement could be a setting stimulus changing the child's expectations and prompting many changes in behavior that might be thought to result from the reinforcement procedure.

Thermal irradiation was applied to selected skin areas to determine whether particular areas demonstrate a greater thermal sensitivity than others in determination of a physiological thermoregulatory response. Modifications in thigh sweating rate were related to the change in temperature of the irradiated skin and the area of skin irradiated by computing a sensitivity coefficient for each skin area. Thermal sensitivity of the face, as measured by its effect on sweating rate change from the thigh, was found to be approximately three times that of the chest, abdomen men and thigh. Lower legs were found to have about one-half the thermal sensitivity of the thigh. A table of weighting factors for calculation of physiological mean skin temperature, based upon thermal sensitivity and area, is presented.

SUMMARY The cardiac output fall and the rate changes observed with halothane-oxygen anaesthesia represent a homeostatic adjustment to greater oxygen extraction per unit volume of blood, secondary to 98 per cent oxygen breathing and to a decreased oxygen demand of the anaesthetized patient. The ability of the heart to restore the pumping function toward control levels by rate change alone strongly challenges the concept that clinical concentrations of halothane expose the myocardium to undue degrees of direct depression. The favourable clinical impressions of clinicians can be reconciled with the findings of the investigators.

SYNOPSIS Auditory brainstem evoked potentials (ABEP's) using the routine 10 per second click rate, and also a 55 persecond stimulus rate, were studied in 17 migraine patients between and during attacks, and in 20 normal subjects.Only in the "migraine during attack" group did the increased stimulus rate change the ABEP's. Similar changeswith increased stimulus rates may be seen in situations of ischemic synaptic dysfunction. Thus, our data supporta vascular pathogenesis of migraine.

Double firing of a motor unit correlates with a transient decrease in its firing rate. The effect cannot be due to collision of the orthodromically conducted first action potential and the apparently distally induced and antidromically conducted second action potential: The interval increment of the motor unit is on an average 40 to 50% and not twofold. Differences between single cells in the degree of inhibition after double discharge could be verified. Some latent effect of inhibition seems to remain after the first discharge following a double discharge. The probable cause of firing rate change after double discharge is either a mixed effect of the antidromic conducting action potential on the motoneuron or a pure Renshaw inhibition.

The Loo-Riegelman method was applied to serum amikacin level data after intravenous and intramuscular administration. Intramuscular amikacin absorption can be described by first-order kinetics, but the absorption rate constant decreased from 1.95 hr-1 at a 125-mg dose to 1.00 hr-1 at a 750-mg dose. This rate change apparently is a physical phenomenon due to differing dosing volumes at different doses and attendant changes in the surface area to volume ratio at the injection site. Amikacin absorption rates on intramuscular injection can be maximized by giving several smaller injections rather than a single larger injection. This phenomenon should be generally observed with aminoglycoside antibiotics and could be partly responsible for reported variations in the absorption rate and the poor predictability of serum concentrations.

We have recently described the electrophysiological basis of a new algorithm for the QT (TX) sensing rate responsive pacemaker. By using the new software program running on the standard programmer it has been possible to simulate the new algorithm in ten patients with complete heart block (seven patients had implanted TX units and three were paced with an external TX pacemaker) during routine exercise testing. In this way a single-blind, intra-patient comparison of the pattern of pacing rate change using both the existing and new algorithms was possible. In nine out of the ten cases the time taken to increase the pacing rate from 70 to 80 bpm was reduced significantly when the new algorithm was used (P = 0.037). Additionally, the correlation between the atrial and ventricular rates in those patients with normal sinus node function (seven patients) was determined. In all cases we have observed a significantly improved correlation between the atrial and ventricular paced rates during exercise with the new algorithm (P less than 0.001).

A case of alternation of T wave with reversal of polarity, independent of any changes of the QRS but apparently greatly influenced by abrupt cycle length change, is presented. Evidence suggests that this phenomenon is indicative of severe myocardial disturbance.