Early Time Period Research Articles

Screening for a new primary cancer in patients with existing metastatic cancer: a retrospective cohort study.

Cancer screening aims to detect malignant disease early in its natural history when interventions might improve patient outcomes. Such benefits are unclear when screening occurs for patients with an existing high risk of death. Our aim was to study the extent of routine cancer screening for a new primary cancer in patients with existing metastatic cancer. We used administrative databases from Ontario to identify a retrospective cohort of adults of eligible screening age (≥ 50 yr) who had a diagnosis of stage IV (metastatic) colorectal, lung, breast or prostate cancer between 2007 and 2012. We calculated the cumulative incidence of cancer screening over time for colorectal and breast cancer. Among the 20 992 patients with metastatic lung, breast or prostate cancer, 2.9%, 6.3% and 13.3% of patients, respectively, underwent testing for colorectal cancer within 1 year of cancer diagnosis. Within 3 years of diagnosis, rates reached 4.1%, 12.3% and 27.5%, respectively (8.5% of all patients). Incidence of colorectal cancer testing was higher among patients who received their diagnoses more recently compared with patients with diagnoses from earlier time periods (p = 0.0143). Among the 10 034 women with metastatic lung or colorectal cancer, 8.7% and 8.0% of patients, respectively, underwent breast cancer screening within 1 year of cancer diagnosis. Within 3 years of diagnosis, screening rates reached 10.2% and 13.1%, respectively. Our findings indicate excessive rates of cancer screening among patients with metastatic cancer who are unlikely to benefit. Further studies are warranted to identify predictors for screening, resource implications, potential and real harms borne by patients, and the impact of a recent Choosing Wisely statement recommending against the practice.

Vaccines in pediatric transplant recipients—Past, present, and future

Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.

Lunati and the island of towers: Obsidian in Nuragic Sardinia

This paper discusses Bronze Age Nuragic obsidian exploitation by combining raw material sourcing with techno-typological analysis of a total of 363 obsidian artifacts from two sites in west-central Sardinia. The results are then combined with previously published data to make broader interpretations about obsidian reduction strategies and island-wide exchange networks, making it one of the largest compilations of data on Nuragic obsidian procurement, production, and consumption to date.These new data add nuance to prior generalizations of Nuragic obsidian consumption as an expedient flake-based technology centered on the exploitation of one primary outcrop of obsidian, in turn highlighting the presence of bladelet production as well as regional differences in source exploitation that are distinct from earlier time periods. Despite such diversity, lunates of SC obsidian are ubiquitous and may have circulated as finished products. In this context, the exchange of obsidian likely acted as a means of regulating social relations across space, in turn structuring the flow of goods, information, and ideas that were key to the creation and maintenances of Nuragic identity.

Changes in practice patterns in male infertility cases in the United States: the trend toward subspecialization

To assess changes in the practice patterns of urologists performing male infertility procedures (vasal reconstruction, sperm retrieval, varicocelectomy) from 2004 to 2015 in the United States. Examination of self-reported procedural volumes from urologists undergoing certification and recertification using case log data provided by the American Board of Urology. The study period was stratified into early (2004-2007) and recent (2012-2015) time periods. Not applicable. None. None. Temporal variations in male infertility practice patterns among different urologic subspecialties between the early and recent time periods. The overall proportion of total male infertility procedures performed by andrologists significantly increased between the early and recent groups (23% to 26%). This growth was driven by a significant increase in the proportion of varicocele repairs being performed by andrologists between the early and recent periods (19% to 25%). Most notably, an assessment of total number of male infertility procedures performed by newly certifying urologists showed that there was a significant increase in the overall proportion of all male infertility procedures being performed by recently trained andrologists (24% to 35%). This significant increase was seen individually among all three types of male infertility procedures. With the increased trend in urologists obtaining fellowship training, male infertility surgical volume is beginning to shift from general urologists to subspecialized andrologists.

Stepfamily Structure and Transfers between Generations in U.S. Families

Unstable couple relationships and high rates of re-partnering have increased the share of U.S. families with stepkin. Yet data on stepfamily structure are from earlier time periods, include only coresident stepkin, or cover only older adults. This paper uses new data on family structure and transfers in the Panel Study of Income Dynamics (PSID) to describe the prevalence and numbers of stepparents and stepchildren for adults of all ages and to characterize the relationship between having stepkin and transfers of time and money between generations, regardless of whether the kin live together. We find that having stepparents and stepchildren is very common among U.S. households, especially younger households. Furthermore, stepkin substantially increase the typical household’s family size; stepparents and stepchildren increase a household’s number of parents and adult children by nearly 40% for married/cohabiting couples with living parents and children. However, having stepkin is associated with fewer transfers, particularly fewer time transfers between married women and their stepparents and stepchildren. The increase in the number of family members due to stepkin is insufficient to compensate for the lower likelihood of transfers in stepfamilies. Our findings suggest that recent cohorts with more stepkin may give less time assistance to adult children and receive less time assistance from children in old age than prior generations.

The Brain/MINDS project aimed at establishing the marmoset as a model organism for neurobiology and establishing the genetic and biochemical elements of their neural development

The brain is the most sophisticated and intricate organ in the body. Billions of neurons interconnect and form distinct regions which process different neural activities. The development of the brain during pregnancy and early post-natal life is extremely sensitive, complex and crucial to proper function over the life of a person. This is the most plastic time of the brain. It is changing constantly and reacting to the different stimuli encountered by the individual. The lack of a particular stimulus can have a profound effect on the later structure and function of the brain. For example, if a newborn mouse has an eye covered so it receives no light, visual cortex, where normally processes binocular visual stimuli, develops to process visual stimuli only from the open eye. This cannot be altered later on even when both eyes are opened; the mouse remains weak in one eye despite there being nothing wrong with the eye itself. Studying this early time period of brain development presents many problems. Investigation is hampered by the difficulty in accessing and manipulating the brain as well as the huge variety of factors that contribute to brain development. Currently, most work is conducted in rodents, primarily because there are a large range of genetic tools available. This is useful to an extent and has demonstrated key findings that appear to be relevant to most mammalian species. However, the human brain is quite different to the mouse brain. It has adapted to very different tasks required of mice compared to humans and therefore there is a knowledge gap to bridge in this area. In addition to this, examination of global gene expression in the brain has only truly become viable in the last 10 years. The same can also be said of the ability to analyse the development process at a biochemical level. Dr Tomomi Shimogori of the RIKEN Center for Brain Science, Japan, has been tackling these difficulties through her work on the molecular mechanisms of brain development. She has worked on rodents, but is now developing a model in the common marmoset based around the creation of a gene atlas. Working on the primate should help fill in the gap between rodent and human. Shimogori explains why the marmoset was chosen: 'One of the biggest advantages of using marmosets as a model animal is that many of its behaviours share similarities with human behaviours, and thus has potential for use in understanding the underlying mechanisms of human brain function and mental disease

Analytical model for heat transfer between vertical fractures in fractured geothermal reservoirs during water injection

Abstract In recent years, the demand for energy has vastly increased due to rapid commercialization. This increasing requirement has put a further strain on the conventional power generation units. In this paper, the problem of water injection into a fractured geothermal reservoir in Cartesian coordinate is considered and an exact analytical solution has been presented to describe the transient temperature distribution and advancement of the thermal front generate due to transient temperature of heat depleted water in a coupled fracture–matrix system at the scale of a single fracture. This solution is able to explain the following phenomena: convection transport in fractures, conduction heat transfers in matrix block and heat flux transfer between rock matrix and fracture. Also, the heat transfer shape factor can be defined by employing the convection-conduction equation in matrix and fracture. The derived analytical solution was used for investigating early and late time periods of heat transfer phenomenon in naturally fractured reservoirs. In addition, a conceptual definition for thermal recovery efficiency has been offered as the rest of included materials. In order to validate the predicted temperature by analytical model in fractured geothermal reservoirs, the presented analytical model is compared with numerical and pervious analytical model.

Chemoradiotherapy versus chemotherapy alone for unresected intrahepatic cholangiocarcinoma: practice patterns and outcomes from the national cancer data base.

Current guidelines recommend chemotherapy (CT) with or without radiotherapy (RT) for unresected intrahepatic cholangiocarcinoma (IC). Although there is currently lack of consensus, previous smaller studies have illustrated the efficacy of local therapy for this population. This investigation evaluated outcomes of chemoradiotherapy (CRT) versus CT alone in unresected IC using a large, contemporary national database. The National Cancer Data Base (NCDB) was queried for primary IC cases (2004-2013) receiving CT alone or CRT. Patients undergoing resection or not receiving CT were excluded, as were those with M1 disease or unknown M classification. Logistic regression analysis ascertained factors associated with CRT administration. Kaplan-Meier analysis evaluated overall survival (OS) between both groups. Cox proportional hazards modeling assessed variables associated with OS. In total, 2,842 patients were analyzed [n=666 (23%) CRT, n=2,176 (77%) CT]. CRT was less likely delivered at community centers, in more recent time periods (2009-2013), to older patients, and in certain geographic locations. Median OS in the CRT and CT groups were 13.6 vs. 10.5 months, respectively (P<0.001). On multivariate analysis, poorer OS was associated with age, male gender, increased comorbidities, treatment at a community center, and treatment at earlier time periods (2004-2008) (P<0.05 for all). Notably, receipt of CRT independently predicted for improved OS (P<0.001). As compared to CT alone, CRT was independently associated with improved survival in unresected IC. These findings support a randomized trial evaluating this question that is currently accruing.

Microbiota and Type 2 immune responses.

The trillions of microbes that colonize mucosal surfaces are critical for educating the immune system and microbial-derived signals continually shape and set the tone of immune responses. Although Type 2 immune responses are important for mediating protection from helminth infection they also underlie atopy and allergy. Microbes modulate Type 2 immune responses through effects on Type 2 cytokines, dendritic cells and regulatory T cells. Microbial colonization in the gut, the lung and the skin during an early and critical time period in immune development appears to be of particular importance for tolerance induction and regulation of aberrant Type 2 immune responses. This is illustrated by studies showing microbial alterations in early life that are associated with allergies later in life.

Outcomes over Time in Patients with Hostile Neck Anatomy Undergoing Endovascular Repair of Abdominal Aortic Aneurysm

PurposeTo assess differences in outcome in an early and later time period in patients with hostile neck anatomy who underwent endovascular aneurysm repair (EVAR). Materials and MethodsThis single-center, institutional review board-approved retrospective study assessed patients who underwent EVAR between 2004 and 2013, divided into 2 time periods: 2004–2008 and 2009–2013. One hundred twenty-five patients had at least 1 hostile neck parameter that met inclusion criteria: 61 of 216 (28%) patients in the early period and 64 of 144 (44%) patients in the late period. Patients in the late group were younger compared to patients in the early group (late group, 74.5 ± 8.8 years vs early group, 77.5 ± 7.5 years; P = .046). No significant differences were observed in hostile neck anatomic factors between the early and late periods. ResultsNo statistical difference was observed in periprocedural factors or outcome measures, except for abdominal aortic aneurysm (AAA) sac regression in the late period compared to the early period (late period, 73.5% vs early period, 55.7%; P = .038). A statistically significant increase was observed in type 1a endoleaks in patients in the late group with suprarenal fixation compared to patients with infrarenal fixation (suprarenal, 27.0% vs infrarenal, 7.9%; P = .025) and in the overall time studied (suprarenal, 20.3% vs infrarenal, 7.6%; P = .045). ConclusionsExcept for AAA sac regression, no changes were observed in periprocedural factors and outcome measures over time in patients with hostile neck who underwent EVAR.

Reassessment of Resuspension Factor Following Radionuclide Dispersal: Toward a General-purpose Rate Constant.

A recent analysis of historical radionuclide resuspension datasets confirmed the general applicability of the Anspaugh and modified Anspaugh models of resuspension factors following both controlled and disastrous releases. While observations appear to have larger variance earlier in time, previous studies equally weighted the data for statistical fit calculations; this could induce a positive skewing of resuspension coefficients in the early time-period. A refitting is performed using a relative instrumental weighting of the observations. Measurements within a 3-d window are grouped into singular sample sets to construct standard deviations. The resulting best-fit equations produce tamer exponentials, which give decreased integrated resuspension factor values relative to those reported by Anspaugh. As expected, the fits attenuate greater error among the data at earlier time. The reevaluation provides a sharper contrast between the empirical models and reaffirms their deficiencies in the short-lived timeframe wherein the dynamics of particulate dispersion dominate the resuspension process.

A generalized Characteristic-Based Split projection method for Navier-Stokes with real fluids

A new computational approach for the general numerical simulation of fluid flows is presented and demonstrated for compressible natural convection flows with real fluid properties. The Characteristic-Based Split finite element method is generalized, and abbreviated as GCBS, in the present work to introduce both pressure-expansion effects in addition to thermal-expansion effects on density within the projection step, in contrast to recent works that preserve only one of those two expansion effects. Moreover, we keep the fluid in thermodynamic equilibrium to support a real equation of state and fluid model. The method retains the full Navier-Stokes equations, transitioning smoothly between compressible and incompressible flows, without special artificial-compressibility methods, special low-Mach-number methods, or other modeling treatments. Neither isothermal or isobaric assumptions are made. The non-linear solution obtained is validated by the linearized solution during the early time period of the simulation. Natural convection in a cavity is explored for its convenience in testing across known benchmark flow regimes, from classical Boussinesq flow to the full Navier-Stokes equations with real fluid models. Results for natural convection in a cavity across Rayleigh numbers, non-dimensional adiabatic temperature gradients, and temperature differences, are obtained across flow regimes with the GCBS method. Classical Boussinesq, Thermodynamic Boussinesq, low-Mach number, and real-gas flows are presented, demonstrating the generalization of the method across flow regimes. Thus, our contribution is to generalize the Characteristic-Based Split method to capture the full Navier-Stokes equations while demonstrating the capability with compressible natural convection.

The Effects of Zoning Regulations along Fault Zone Areas on Land Development and Property Values after the 921 Chi-Chi Earthquake in Taiwan

Earthquakes are widely recognized as unpredictable and infrequent disasters that result in serious impacts on human settlements. Land use planning is one non-structural measure used to eliminate disaster risk by steering future development away from the existing built environment and enforcing particular structural engineering measures according to the disaster risk. However, arguments have arisen about applying land use planning to earthquake risk areas, as this serves as a type of disaster risk information disclosure that might impact the willingness to develop land or property value. Therefore, this study uses the spatial autocorrelation coefficient to examine the impact of land use planning on both land use and property transactions in the Chelungpu fault zone area (15 m from each side of the fault line) in Taiwan. The overall impacts with and without zoning regulation in the fault zone area are explored. The results demonstrate that parcels that changed to building use in the earlier time period (1995–2008) are located distant from those maintaining the same building use, whereas, later, building use (2008–2014) is located on or nearby the fault zone area. In addition, the most recently constructed buildings are located in or close to the fault zone area and have a relatively higher property price. The legal zoning regulation along the fault zone for building use requires lower height and less intensive building, which might help mitigate the potential impact of future earthquakes.

Clusters of Suicidal Events Among Young People: Do Clusters from One Time Period Predict Later Clusters?

We sought to compare clusters of suicidal events between two different time periods and examine the extent to which earlier clusters predict later clusters. We included data on suicides and suicide attempts from New South Wales between July 2001 and June 2012 and Western Australia between January 2000 and December 2011. Suicide attempts included admissions to hospital for deliberate self-harm and suicides were deaths due to deliberate self-harm. We combined data on suicides and suicide attempts and grouped them into two equal time periods. We detected clusters in each period using Poisson discrete scan statistics adjusted for socio-economic status. We estimated the predictive values of earlier clusters on later clusters. The results showed that clusters from earlier time period had a moderate power (36%) in predicting later clusters. During the later time period, some additional cluster areas (14%) were found and some earlier cluster areas subsided (64%). Historical clusters predict 36% of the subsequent clusters, which is probably not sufficient for targeting interventions. Our study highlights the need for other strategies to detect emerging clusters, for example, up-to-date data.

Shifts in Forest Structure in Northwest Montana from 1972 to 2015 Using the Landsat Archive from Multispectral Scanner to Operational Land Imager

There is a pressing need to map changes in forest structure from the earliest time period possible given forest management policies and accelerated disturbances from climate change. The availability of Landsat data from over four decades helps researchers study an ecologically meaningful length of time. Forest structure is most often mapped utilizing lidar data, however these data are prohibitively expensive and cover a narrow temporal window relative to the Landsat archive. Here we describe a technique to use the entire length of the Landsat archive from Multispectral Scanner to Operational Land Imager (M2O) to produce three novel outcomes: (1) we used the M2O dataset and standard change vector analysis methods to classify annual forest structure in northwestern Montana from 1972 to 2015, (2) we improved the accuracy of each yearly forest structure classification by applying temporal continuity rules to the whole time series, with final accuracies ranging from 97% to 68% respectively for two and six-category classifications, and (3) we demonstrated the importance of pre-1984 Landsat data for long-term change studies. As the Landsat program continues to acquire Earth imagery into the foreseeable future, time series analyses that aid in classifying forest structure accurately will be key to the success of any land management changes in the future.

Stem Cell Transplantation for Light Chain Amyloidosis: Decreased Early Mortality Over Time.

Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.

Longitudinal study of the association between thrombocytopenia and retinopathy of prematurity

An association between thrombocytopenia and retinopathy of prematurity (ROP) has been suggested but not been studied longitudinally. We sought to identify the time period in postnatal development during which thrombocytopenia and the subsequent development of severe ROP are associated. This was a retrospective case-control study of 100 subjects who received laser photocoagulation for type 1 ROP between 2005 and 2009 and 100 controls with no ROP or only stage 1 ROP. The proportions of infants with thrombocytopenia, defined as a serum platelet level of <150,000/μL, among cases versus controls were compared on a weekly basis from birth through the time of laser during early (postmenstrual age [PMA] weeks 24-28), middle (PMA weeks 29-34), and late (PMA weeks 35-38) time periods. Main outcome measures were odds ratios for the association between thrombocytopenia and type 1 ROP from multivariate logistic regression models adjusted for gestational age, birth weight, culture-proven sepsis, and necrotizing enterocolitis. Thrombocytopenia was significantly associated with severe ROP during PMA weeks 24-28 (adjusted OR, 4.7; 95% CI, 2.0-1.1; P=0.001) and 29-34 (adjusted OR, 2.8; 95% CI, 1.4-5.6; P=0.006), but not during weeks 35-38 (adjusted OR, 2.0; 95% CI, 0.9-4.3; P=0.10). Thrombocytopenia from birth through 34weeks' PMA was associated with subsequent severe ROP. This time period corresponds to a period of poor retinal vascular growth, suggesting a possible proangiogenic effect of platelets in normal retinal vascular development in infants at risk for ROP.

Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute Lymphoblastic Leukemia Patients in Maintenance Therapy.

Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has become a significant long-term concern. Excessive weight gain often occurs during treatment, particularly during induction and the first 6 months of maintenance therapy, and it may be potentially modifiable. This retrospective study aimed to evaluate the impact of an early, 3-visit nutrition intervention on weight gain during maintenance therapy in ALL patients. Medical records of the intervention group were compared with historical controls who were treated on the same ALL treatment protocols during an earlier time period. Anthropometrics were collected throughout intensive therapy and at every monthly visit during the first 12 months of maintenance therapy. In total, 67 patients were evaluated (33 in the intervention group and 34 in the control group). After controlling for significant predictors of body mass index (BMI) z-scores in maintenance therapy-including higher BMI at diagnosis and weight gain throughout intensive therapy-the intervention group demonstrated more controlled weight gain during maintenance therapy (P<0.0001). A 3-visit nutrition intervention was effective in attenuating weight gain trends during ALL maintenance therapy.

Permit banking in emission trading: Competition, arbitrage and linkage

Several existing or proposed climate policies have considered bankable permits in a cap-and-trade (C&T) program that covers beyond a single sector, e.g., electric power, or allows the program to link to external C&T programs in other regions. This paper develops a model of permit banking under imperfect competition and imperfect inter-temporal arbitrage, in which the firms in one dominant sector can exert market power in both product and permit markets, while those in other sectors or linked programs are perfectly competitive. A simple analytical model is developed to generate contestable hypothesis. We further extend the model to account for the physical power system, institutional rules and market conditions, and then apply it to the Pennsylvania-Jersey-Maryland (PJM) market. We show that if the dominant firm has market power, then the permit price rises at a higher rate than the discount rate, contrary to perfectly competitive permit market, where the permit price rises at the discount rate following the classic Hotelling's rule. Furthermore, under a declining emissions cap system with the permits front-loaded in early time periods, the dominant firm has an incentive to suppress the permit prices (monopsony) when buying the permits in early periods, and then inflate the permit prices (monopoly) when selling them in later periods. Numerical results of the PJM case are consistent with the analytical conclusion.

Hospital Readmission Rates Following AMI: Potential Interventions to Improve Efficiency.

Quality of care utilization measures for patients admitted to the hospital with an acute myocardial infarction (AMI) include length of stay (LOS) and 30-day readmission rates. Our aim was to test whether efforts resulting in reduced LOS in patients diagnosed as having AMI would result in a higher risk of readmission within 30 days of hospital discharge and whether specific interventions could be targeted to reduce readmissions. Using data supplied by the Veterans Affairs Inpatient Evaluation Center, we analyzed both the readmissions within 30 days of an AMI and LOS and determined the timing of readmissions and associated diagnoses. During 2013-2015, 35 (13.3%) of 263 patients with AMI were readmitted within 30 days of discharge compared with 19 (13.4%) of 142 patients during 2016 (not significant). During the same time, LOS was <3 days in most patients. From 2013 to 2015, the initial hospital time was 6 ± 6 days, whereas time out of the hospital before readmission was 11 ± 8 days; these times did not differ from 2016. Initial therapeutic decisions were based on coronary anatomy in >90% of patients with a decision to proceed with revascularization in most patients. Diagnoses during readmission to the hospital were also similar during early and later time periods and most frequently were a result of either coronary artery bypass grafting-related complications from the initial hospitalization or elective coronary artery bypass grafting. Acute coronary syndrome-related diagnoses and recurrent noncardiac causes of chest pain also were common diagnoses during both time periods and did not involve extensive workup during the readmission. Readmissions for patients with AMI were stable during a 4-year period, at a time that efforts to reduce LOS were emphasized. Because a significant proportion of readmissions involved noncardiac sources of chest pain, improved communication between the emergency department and in-patient cardiology services at the time of triage may be a feasible way to improve efficiency of utilization.