Threshold Amount Research Articles

Small Volumes of Feed Can Trigger Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux in the Right Lateral Position in Infants

To investigate the threshold amount of constantly infused feed needed to trigger lower esophageal sphincter relaxation (TLESR) in the right lateral position (RLP) and left lateral position (LLP). Eight healthy infants (3 male; gestational age: 32.9 +/- 2.4 weeks; corrected age: 36.1 +/- 1.3 weeks) were studied using an esophageal impedance-manometry catheter incorporating an intragastric infusion port. After tube placement, infants were randomly positioned in RLP or LLP. They were then tube-fed their normal feed (62.5 [40 to 75] mL) at an infusion rate of 160 mL/h. Recordings were made during the feed and 15 minutes thereafter. The study was repeated with the infant in the opposite position. More TLESRs were triggered in the RLP compared with LLP (4.0 [3.0 to 6.0] vs 2.5 [1.0 to 3.0], P = .027). First TLESR occurred at a significantly lower infused volume in RLP compared with LLP (10.6 +/- 9.4 vs 21.0 +/- 4.9 mL, P = .006). The percentage of feed infused at time of first TLESR was significantly lower in RLP compared with LLP (17.6% +/- 15.5% vs 35.4% +/- 8.02%, P = .005). In the RLP, TLESRs and gastroesophageal reflux are triggered at volumes unlikely to induce gastric distension.

Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum)

The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment.

On nonlinearity of petroleum formation

A nonlocal dynamic model of petroleum formation is used to explore possible causes and consequences of the nonlinear behavior of large petroleum systems. As a result of this nonlinearity, migration and accumulation of oil starts only after hydrocarbons in a reservoir reach a threshold amount. Significant differences in the amount of in-place resources in macroscopically similar petroleum systems may be associated with minor random changes in initial conditions.

An alternative methodology for the prediction of adherence to anti HIV treatment

BackgroundSuccessful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS. Causes of treatment failure are either related to drug resistance and/or insufficient drug levels in the blood. Severe side effects, coupled with the intense nature of many regimens, can lead to treatment fatigue and consequently to periodic or permanent non-adherence. Although non-adherence is a recognised problem in HIV treatment, it is still poorly detected in both clinical practice and research and often based on unreliable information such as self-reports, or in a research setting, Medication Events Monitoring System caps or prescription refill rates. To meet the need for having objective information on adherence, we propose a method using viral load and HIV genome sequence data to identify non-adherence amongst patients.Presentation of the hypothesisWith non-adherence operationally defined as a sharp increase in viral load in the absence of mutation, it is hypothesised that periods of non-adherence can be identified retrospectively based on the observed relationship between changes in viral load and mutation.Testing the hypothesisSpikes in the viral load (VL) can be identified from time periods over which VL rises above the undetectable level to a point at which the VL decreases by a threshold amount. The presence of mutations can be established by comparing each sequence to a reference sequence and by comparing sequences in pairs taken sequentially in time, in order to identify changes within the sequences at or around 'treatment change events'. Observed spikes in VL measurements without mutation in the corresponding sequence data then serve as a proxy indicator of non-adherence.Implications of the hypothesisIt is envisaged that the validation of the hypothesised approach will serve as a first step on the road to clinical practice. The information inferred from clinical data on adherence would be a crucially important feature of treatment prediction tools provided for practitioners to aid daily practice. In addition, distinct characteristics of biological markers routinely used to assess the state of the disease may be identified in the adherent and non-adherent groups. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients.

Probabilistic design of a riverine early warning source water monitoring systemA paper submitted to the Journal of Environmental Engineering and Science.

Source water protection involves safeguarding water supplies from contamination and depletion. Despite best efforts, spills cannot always be prevented from entering a source water body. However, many spills can be prevented from entering a drinking water treatment plant if an early warning source water monitoring station is used. These stations provide downstream water utilities with advanced notification of spills so the utilities have time to implement their responses. This paper addresses the design of an early warning monitoring station for a riverine source of drinking water. Riverine water supplies face many threats related to accidental spills, which are inherently uncertain in nature. Therefore, designing a monitoring station for the detection of these events requires a probabilistic modelling approach. The design objectives include maximizing the probabilities of detection and of having a threshold amount of warning time. The methodology is applied to a water supply intake on the Grand River in southern Ontario.

Steps Per Day

In older adults, as in younger individuals, habitual moderate-intensity physical activity is associated with a reduced risk of various chronic health conditions, including certain types of cardiovascular and musculoskeletal disease and certain forms of cancer. However, the pattern of physical activity associated with such benefits remains unclear. One problem is that most investigators have examined patterns of physical activity using either subjective questionnaires or accelerometer or pedometer measurements limited to a single week, despite clear evidence of both the unreliability/invalidity of questionnaires and seasonal changes in activity patterns. Since 2000, we have thus conducted an interdisciplinary study examining the habitual physical activity and health of elderly people living in a medium-sized Japanese town (the Nakanojo Study). In about one-tenth of some 5000 available subjects aged > or =65 years, physical activity has already been assessed continuously for 24 h/day for >8 years using a specially adapted pedometer/accelerometer. This device has a storage capacity of 36 days and can distinguish >10 intensities of physical activity (expressed in metabolic equivalents [METs]). Data have to date been summarized as daily step counts and daily durations of activity of <3 and >3 METs, averaged over a 1-year period. This article provides a detailed overview of both factors influencing habitual physical activity and relationships between such activity and health in an elderly population. To date, analyses have been cross-sectional in type. Substantial associations have been noted between the overall health of participants and both the daily duration of effort undertaken at an intensity of >3 METs and the daily step count. In men, the extent of health is associated more closely with the daily duration of activity of >3 METs than with the daily step count, whereas in women, the association is closer for the step count than for the duration of activity >3 METs. In both sexes, the threshold amount of physical activity associated with better health is greater for physical than for mental benefits: >8000 versus >4000 steps/day and/or >20 versus >5 min/day at an intensity >3 METs, respectively. In other words, better physical health is seen in those spending at least 20 min/day in moderate walking (at a pace of around 1.4 m/s [5 km/h]) and a further >60 min of light activity per day. In contrast, better mental health is associated with much smaller amounts of deliberate physical activity. The daily step count and the daily durations of activity of <3 and >3 METs are all influenced by meteorological factors, particularly precipitation and mean ambient temperature. Activity decreases exponentially to about 4000 steps/day as precipitation increases. Excluding the influence of rainfall, the daily step count peaks at a mean outdoor temperature of around 17 degrees C; above and especially below such readings, physical activity decreases as a quadratic function of temperature. Seasonal changes in microclimate should thus be considered when designing interventions intended to increase the habitual physical activity of elderly people. The observed associations between physical activity and health outcomes point to a need for longitudinal analyses; these should examine potential causal interpretations of the current findings and elucidate possible additional mediating variables.

How Should Objectively Measured Physical Activity Data Be Used Analytically?

Dear Editor-in-Chief: Accelerometers now allow researchers to monitor the intensity and duration of exercise and nonexercise activities with considerable precision. However, there is a need for agreed procedures to summarize the resulting mass of data. Pate et al. (5) have suggested distinguishing sedentary (1.0-1.5 metabolic equivalents (METs)) and/or light activities (1.6-2.9 METs) as well as moderate (3.0-6.0 METs) and/or vigorous activities (≥6.1 METs). They presented 13 h of accelerometry data for two persons with similar total energy expenditures (26 vs 24 METs·h−1) but markedly different activity patterns (sedentary, 25% vs 70%; light, 75% vs 23%; moderate to vigorous, 0% vs 7%). Such classification becomes important when testing associations between activity patterns and health outcomes. A study of seniors from Nakanojo (1-4, 6-8) has, since 2000, used specially adapted pedometer/accelerometers (modified Kenz Lifecorders) to establish detailed physical activity patterns 24 h·d−1 over an entire year. Findings have been summarized as daily step counts and daily durations of sleeping and sedentary, light, moderate, and vigorous activities. Our observations (1) demonstrate close correlations between the daily step count (x) and the daily duration of moderate-to-vigorous activity (y) (y = [1.96 · 10−7] x2 + [1.16 · 10−3] x; r2 = 0.93). Those with a higher daily step count are also likely to engage in more moderately vigorous activity. It seems that the little activity sedentary older adults take is usually of light intensity, whereas active individuals engage in significant periods of what for this age group is moderate activity. In an average individual taking 7000 steps·d−1, a quarter of the total effort (15 min·d−1) is moderate to vigorous; this percentage is lower (<20%, <5 min·d−1) in those taking <4000 steps·d−1 and higher (>30%, >30 min·d−1) in those taking >10,000 steps·d−1. Pate et al. (5) have recommended exploiting accelerometry to examine associations between activity levels and health outcomes. However, substantial data of this type already exist. Our studies (1) indicate that measures of physical and psychosocial health as diverse as depression (8), a poor health-related quality of life (7), arteriosclerosis, osteoporosis (3), sarcopenia, a lower level of physical fitness (2), and metabolic syndrome (4) are all associated with both the intensity and the total volume of habitual physical activity undertaken. The threshold amount of physical activity associated with better health seems greater for physical than for mental benefits: >8000 versus >4000 steps·d−1 and/or >20 versus >5 min·d−1 at a moderate-to-vigorous intensity. Physical health is better in seniors spending at least 20 min·d−1 in brisk walking and a further >50 min·d−1 in light activity, whereas mental health is associated with much smaller amounts of deliberate physical activity. Moreover, and perhaps contrary to an emphasis on sedentariness, physical and psychosocial health seems greater in individuals who undertake a larger proportion of their daily activity at a moderate-to-vigorous intensity. Yukitoshi Aoyagi, Ph.D. Exercise Sciences Research Group, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, Japan Roy J. Shephard, M.D., Ph.D., LL.D., FACSM Faculty of Physical Education and Health, University of Toronto, Toronto, Ontario, Canada

Proton-pump inhibitor utilization associated with the change to nonpreferred formulary status for esomeprazole in the TRICARE formulary.

inhibitor (PPI) esomeprazole in the third copayment tier on the TRICARE formulary on July 17, 2005. The change to nonpreferred formulary status for esomeprazole included a $13 copayment increase (from $9.00 to $22.00) for either a 30-day supply purchased from a community pharmacy or a 90-day supply purchased from the mail-order pharmacy and a $0 copayment if obtained from a military pharmacy but with a prior authorization (PA) requirement. The change to nonpreferred formulary status was designed to encourage the use of PPIs other than esomeprazole and to increase the use of the mail-order pharmacy for esomeprazole purchases. To quantify changes in (a) the TRICARE beneficiary utilization of esomeprazole relative to other PPIs and (b) the pharmacy settings used for filling esomeprazole prescriptions following implementation of a copayment increase and nonpreferred formulary status for esomeprazole. A census of outpatient pharmacy fill records for prescription acid-reducing medications (PPIs, histamine-2 blockers, misoprostol, and sucralfate) obtained by beneficiaries aged 18 years or older from January 1, 2005, through December 31, 2006, was examined. Interrupted time series regression analyses without a control group were used to compare the utilization of esomeprazole relative to other PPIs, as well as the pharmacy setting used to obtain esomeprazole, in the months before and after the formulary change. The rates of continued esomeprazole use, switching to other prescription PPIs (lansoprazole, omeprazole, pantoprazole, and rabeprazole), switching to non-PPI prescription acid-reducing drugs, and discontinued prescription acid-reducing medication use among existing esomeprazole users (i.e., beneficiaries who obtained esomeprazole as the last PPI fill before the formulary change) were calculated overall and for each pharmacy setting used prior to the formulary change. Over the 24-month study period from January 1, 2005, through December 31, 2006, the total numbers of PPI fills and PPI users increased by 8.5% and 9.0%, respectively, and the number of esomeprazole users decreased by 4.6%. Of esomeprazole users, the percentages of individuals obtaining esomeprazole from military pharmacies and community pharmacies, respectively, decreased from 1.7% to 1.1% and from 89.7% to 81.7%, while the percentage of individuals obtaining esomeprazole from the mail-order pharmacy increased from 8.8% to 17.6%. Time series analysis yielded a positive, statistically significant growth in esomeprazole fills (beta1=0.114; P=0.012) during the 6-month pre-intervention period (January through June 2005) and a significant reduction in August 2005 (beta2=-5.0%; P<0.001), the month immediately following the formulary change. During the 17-month post-intervention period (August 2005 through December 2006), no statistically significant change in trend for esomeprazole fills (beta3=-0.0265; P=0.534) was observed, although a small increase in the raw number of esomeprazole fills was noted. Among the 117,801 existing esomeprazole users, 86,386 (73.3%) continued using esomeprazole, 17,676 (15.0%) switched to other prescription PPIs, 679 (0.6%) used only non- PPI prescription therapy, and 13,060 (11.1%) discontinued all prescription acid-reducing pharmacotherapy after the formulary change. Significantly higher PPI switching and acid-reducing therapy discontinuation rates were observed among men aged 18-44 years and in TRICARE enrollees relative to women, those over 45 years of age, and those who used other health insurance (P<0.001). Individuals who used military pharmacies, where a PA requirement was implemented, were more likely to change pharmacy settings to obtain esomeprazole (43.8%) than were users of community pharmacies (11.9%) or the mail-order pharmacy (22.8%). Mail-order pharmacy users were less likely to discontinue acid-reducing pharmacotherapy (4.9%) than were community (11.9%) or military (12.9%) pharmacy users (P<0.05). After adjustment for serial correlation, the formulary change was associated with a migration of approximately 5% of all PPI fills and 25% of esomeprazole fills to the preferred PPIs in the first post-intervention month. Over the 17-month post-intervention period, the trend toward increased esomeprazole use was slowed and use of the mail-order pharmacy for esomeprazole fills nearly doubled. Our observed PPI switch rate of 15.0% resembled the rate observed for another insured population that experienced a similar formulary restructuring, but was substantially lower than the rates reported for more sizeable formulary changes. Thus, the present study's copayment differentials for third-tier medications ($19 compared with tier 1 and $13 compared with tier 2 copayments) may be less than the threshold amount required to optimize switching to preferred PPIs.

Optically Transparent, Amphiphilic Networks Based on Blends of Perfluoropolyethers and Poly(ethylene glycol)

Amphiphilic networks of perfluoropolyethers (PFPE) and poly(ethylene glycol) (PEG) have been achieved to yield optically transparent, mechanically robust films over a wide range of compositions. Telechelic diols of these oligomers were transformed to a photocurable dimethacryloxy form (DMA) and free radically cured at various composition weight ratios to yield free-standing films. Clear and colorless amphiphilic networks could be achieved when low molar mass versions of both the PFPE-DMA (1 kg/mol) and the PEG-DMA (550 g/mol) were used. The bulk morphologies of the samples were extensively characterized by a variety of techniques including ultraviolet-visible spectroscopy, differential scanning calorimetry, dynamic mechanic thermal analysis, small-angle X-ray scattering, atomic force microscopy, X-ray photoelectron spectroscopy, and optical microscopy, which strongly suggest that nanoscopic to macroscopic phase-separated materials could be achieved. By incorporating a threshold amount of PFPEs into PEG-based hydrogel networks, water swelling could be significantly reduced, which may offer a new strategy for a number of medical device applications. Along these lines, strong inhibition of nonspecific protein adsorption could be achieved with these amphiphilic network materials compared with an oligo(ethylene glycol)-based self-assembled monolayer coated surface.

Systematic review: tolerable amount of gluten for people with coeliac disease

The threshold amount of gluten in 'gluten-free' products that can be tolerated by people with coeliac disease is unclear. To investigate the threshold amount of gluten and the threshold concentration of gluten in food products that can be tolerated by people with coeliac disease. Systematic review of studies published between 1966 and May 2007. The data sources used were MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and reference lists of retrieved articles. We included studies that evaluated the amount of dietary gluten or the concentrations of gluten in food products that can be tolerated by people with coeliac disease whatever their design, method or language of publication. Thirteen studies (three randomized controlled, one cohort, two crossover, and seven cross-sectional) met the inclusion criteria. The daily amount of tolerable gluten varied widely between studies. Whilst some patients tolerated an average of 34-36 mg of gluten per day, other patients who consumed about 10 mg of gluten per day developed mucosal abnormalities. The effect of the consumption of 'gluten-free' products with different degrees of gluten contamination was also inconsistent. The amount of tolerable gluten varies among people with coeliac disease. Although there is no evidence to suggest a single definitive threshold, a daily gluten intake of <10 mg is unlikely to cause significant histological abnormalities.

Self-Enforcing Stochastic Monitoring and the Separation of Debt and Equity Claims

We study the incentive issues associated with self-enforcing stochastic monitoring in a model of investment and production. The efficient contract features a debt-like payment with a threshold in terms of the reported output in which all of the reported output is taken up to the threshold if monitoring doesn’t occur and all of the output is taken if monitoring does occur. An output report above the threshold leads to zero probability of monitoring and just the threshold amount being paid out. The efficiency gap between the self-enforcing contract and the commitment constraint is minimized when the monitors holds no part of the residual claim on the firm, which we associate with equity. Misreporting by the manager is an important component of the efficient contract.

Estimation of Benchmark Dose as the Threshold Amount of Alcohol Consumption for Blood Pressure in Japanese Workers

In order to determine the threshold amount of alcohol consumption for blood pressure, we calculated the benchmark dose (BMD) of alcohol consumption and its 95% lower confidence interval (BMDL) in Japanese workers. The subjects consisted of 4,383 males and 387 females in a Japanese steel company. The target variables were systolic, diastolic, and mean arterial pressures. The effects of other potential covariates such as age and body mass index were adjusted by including these covariates in the multiple linear regression models. In male workers, BMD/BMDL for alcohol consumption (g/week) at which the probability of an adverse response was estimated to increase by 5% relative to no alcohol consumption, were 396/315 (systolic blood pressure), 321/265 (diastolic blood pressure), and 326/269 (mean arterial pressures). These values were based on significant regression coefficients of alcohol consumption. In female workers, BMD/BMDL for alcohol consumption based on insignificant regression coefficients were 693/134 (systolic blood pressure), 199/90 (diastolic blood pressure), and 267/77 (mean arterial pressure). Therefore, BMDs/BMDLs in males were more informative than those in females as there was no significant relationship between alcohol and blood pressure in females. The threshold amount of alcohol consumption determined in this study provides valuable information for preventing alcohol-induced hypertension.

Undamaged DNA Transmits and Enhances DNA Damage Checkpoint Signals in Early Embryos

In Xenopus laevis embryos, the midblastula transition (MBT) at the 12th cell division marks initiation of critical developmental events, including zygotic transcription and the abrupt inclusion of gap phases into the cell cycle. Interestingly, although an ionizing radiation-induced checkpoint response is absent in pre-MBT embryos, introduction of a threshold amount of undamaged plasmid or sperm DNA allows a DNA damage checkpoint response to be activated. We show here that undamaged threshold DNA directly participates in checkpoint signaling, as judged by several dynamic changes, including H2AX phosphorylation, ATM phosphorylation and loading onto chromatin, and Chk1/Chk2 phosphorylation and release from nuclear DNA. These responses on physically separate threshold DNA require gamma-H2AX and are triggered by an ATM-dependent soluble signal initiated by damaged DNA. The signal persists in egg extracts even after damaged DNA is removed from the system, indicating that the absence of damaged DNA is not sufficient to end the checkpoint response. The results identify a novel mechanism by which undamaged DNA enhances checkpoint signaling and provide an example of how the transition to cell cycle checkpoint activation during development is accomplished by maternally programmed increases in the DNA-to-cytoplasm ratio.

Channel width response to differential uplift

The role of channel width and slope adjustments to differential uplift in rivers within actively deforming terrains remains contentious. Here high‐resolution topographic surveying of formerly antecedent outwash channels demonstrates marked changes in channel width as a primary response to differential uplift. For five Late Quaternary alluvial paleochannels crossing small folds along the active Ostler fault zone of southern New Zealand, nearly continuous measurements of paleochannel width and concomitant incision reveal abrupt narrowing of widths toward minimum values at channel positions coincident with the initial uplift. When the magnitude of differential uplift is sufficiently small, narrowing alone permits these channels to remain antecedent. In the context of a unit stream power model for fluvial erosion, observed limits on the magnitude of channel narrowing suggest that above some threshold amount of differential uplift, continued incision requires concomitant changes in channel gradient. Thus when crossing small growing folds, alluvial rivers simply narrow their channels, whereas larger folds that demand greater incision prompt an initial narrowing followed by channel steepening.

613 応力の均一化を目標とした平面構造設計 : しきい値による形状への影響(GS-1 FEM解析法)

613 応力の均一化を目標とした平面構造設計 : しきい値による形状への影響(GS-1 FEM解析法)

Extravascular lung water following resuscitation of hemorrhagic shock in swine: comparison between Ringers' lactate and normal saline

Pulmonary edema is a common consequence of hemorrhagic shock resuscitation. The type and amount of fluid used in resuscitation may be important determinants of the amount of edema formed. Ringers' lactate (RL) and normal saline (NS) remain common resuscitative fluids. These experiments were designed to measure the extravascular lung water (EVLW) after resuscitation from hemorrhagic shock with RL vs NS, to determine whether the fluid type results in differences in the amount of EVLW, and to determine whether there exists a threshold amount of fluid that results in the development of edema.

Nanoionics phenomenon in proton-conducting oxide: Effect of dispersion of nanosize platinum particles on electrical conduction properties

High-temperature proton conductors are oxides in which low-valence cations are doped as electron acceptors; the incorporation of water molecules into the oxides results in the formation of protonic defects that act as charge carriers. Since the protons thus formed are in equilibrium with other electronic defects, electrons and holes, the oxides possibly have different proton-conduction properties at and near boundaries when they are in contact with another phase. In this paper, we present our recent experimental observation of a marked change in the electrical properties of a proton conductor upon the dispersal of fine platinum particles in the oxide. First, the material shows extremely low electrical conductivity in comparison with the original proton-conducting perovskite. Second, there was a threshold amount of platinum at which such a drop in conductivity occurred. A percolation model is employed to explain these experimental results; the fine platinum particles dispersed in the proton-conducting oxide wears highly resistive skin that is formed due to shifts in defect equilibriums, which prevents ionic/electronic conduction. The experiments suggest that the ion-conducting properties of oxides can be varied by introducing interfaces at a certain density; nanoionics is a key to yielding enhanced and/or controlled ionic conduction in solids.

Currency Competition: A Partial Vindication of Hayek

This paper establishes the existence of equilibria for environments in which outside money is issued competitively. Such equilibria are typically believed not to exist because of a classic overissue problem: if money is valued in equilibrium, an issuer produces money until its value is driven to zero. By backward induction, money cannot have value in the first place. However, for any given finite amount of money outstanding, a monetary economy typically has two equilibria. In one, money has value; in the other, money is not valued because no one expects it to be valued. This paper takes this latter equilibrium seriously and shows that trigger strategies eliminate the overissue problem if agents have beliefs of the following type: if an issuer produces money beyond some threshold amount, then the issuer's money has no value. This result is very general, applying to any monetary economy in which equilibria with and without valued money exist if the money supply is finite. The paper also compares the allocation achieved by a monopolist to that achieved with competitive issuance in both a search and an overlapping-generations environment. The results depend on the environment considered, but two general conclusions arise. First, it is ambiguous whether competitive issuers can achieve a more desirable allocation than a monopolist. Second, with competitive issuance, a licensing agency can always improve on pure laissez-faire and achieve the efficient allocation in the long run.

Modulation of the Viral ATPase Activity by the Portal Protein Correlates with DNA Packaging Efficiency

DNA packaging in tailed bacteriophages and herpesviruses requires assembly of a complex molecular machine at a specific vertex of a preformed procapsid. As in all these viruses, the DNA translocation motor of bacteriophage SPP1 is composed of the portal protein (gp6) that provides a tunnel for DNA entry into the procapsid and of the viral ATPase (gp1-gp2 complex) that fuels DNA translocation. Here we studied the cross-talk between the components of the motor to control its ATP consumption and DNA encapsidation. We showed that gp6 embedded in the procapsid structure stimulated more than 10-fold the gp2 ATPase activity. This stimulation, which was significantly higher than the one conferred by isolated gp6, depended on the presence of gp1. Mutations in different regions of gp6 abolished or decreased the gp6-induced stimulation of the ATPase. This effect on gp2 activity was observed both in the presence and in the absence of DNA and showed a strict correlation with the efficiency of DNA packaging into procapsids containing the mutant portals. Our results demonstrated that the portal protein has an active control over the viral ATPase activity that correlates with the performance of the DNA packaging motor.

CMS Describes New System For Paying Psychiatric Facilities

Back to table of contents Previous article Next article Professional NewsFull AccessCMS Describes New System For Paying Psychiatric FacilitiesMark MoranMark MoranSearch for more papers by this authorPublished Online:7 Apr 2006https://doi.org/10.1176/pn.41.7.0016Inpatient psychiatric facilities would receive an average 3.2 percent increase in their Medicare payment rates for discharges occurring on or after July 1, 2006, under a proposed rule issued by the Centers for Medicare and Medicaid Services (CMS).The payment increase would affect approximately 1,800 inpatient psychiatric facilities, including freestanding psychiatric hospitals, certified psychiatric units in general acute care hospitals, and critical access hospitals that are paid under the inpatient psychiatric facility Prospective Payment System (PPS).The PPS for inpatient psychiatric hospitals was mandated by the Medicare, Medicaid, and SCHIP Balanced Budget Refinement Act (BBRA) of 1999 and made effective January 1, 2005, ending a 20-year exemption from prospective payment (Psychiatric News, December 3, 2004).Payments for inpatient psychiatric facilities under the PPS are based on a single federal per diem rate that includes both inpatient operating and capital-related costs. The proposed per diem rate for Rate Year (RY) 2007 is $594.66, up from $575.95 in RY 2006, according to the CMS.This base rate is adjusted for four patient characteristics: age, diagnosis-related group (DRG) assignment, the presence of certain other diseases or conditions (comorbidities), and the patient's length of stay. The base rate is also adjusted to reflect the following facility characteristics: the presence or lack of a qualifying emergency department, teaching status, rural location, and each facility's wage index.In this first update to the system, CMS is proposing a number of refinements to the payment policies affecting inpatient psychiatric facilities. Among the most critical is a proposed redefinition of labor markets.Irvin (Sam) Muszynski, J.D., director of APA's Office of Healthcare Systems and Financing, explained that one effect of this is that many rural hospitals would be reclassified into urban areas and thereby lose their favorable 17 percent facility adjustment established to support the financial stability of rural facilities.“We think this is a problem and will recommend that it be fixed so these hospitals will not be negatively affected,” Muszynski said.A second feature is a proposal to make uniform the time requirements for certification and recertification of patients. Under the CMS proposal, certification would be required for all hospitals and units at the time of admission—or as soon thereafter as is reasonable—and the first recertification would be required as of the 12th day.“We are opposing this and will recommend that recertification be at the 18th day, as currently required,” Muszynski said.Other issues addressed in the proposed payment update include the following:A proposal to adopt a new method of determining inflation in the costs of goods and services provided in inpatient psychiatric facilities reflecting inflation in three types of hospitals that are currently excluded from the inpatient PPS for acute care hospitals: inpatient rehabilitation facilities, inpatient psychiatric facilities, and long-term-care hospitals.A proposal to increase the fixed dollar-loss threshold amount for outlier payments from $5,700 to $6,200 to keep overall outlier payments at 2 percent of total payments as per diem rates increase. This threshold is the amount by which the hospital's costs for treating a case must exceed the Medicare payment amount for that case before Medicare will make an additional payment to the facility.A proposal to increase payment for electroconvulsive therapy (ECT) based on the latest hospital median cost data for ECT.The proposed rule was released January 13 and published in the January 23 Federal Register.At press time, APA's Department of Government Relations was preparing comments about the proposed rule that will address, among other issues, the following: interrupted stays, ICD-9-CM coding issues, physician recertification, and same-day transfers (when a patient is admitted to an inpatient psychiatric facility and is later transferred to another type of facility on the same day). ▪ ISSUES NewArchived