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PubMed2004

HIV-positive youth's perspectives on the Internet and e-health.

BACKGROUND: Globally, half of all new HIV infections occur among young people. Despite this incidence, there is a profound lack of resources for HIV-positive youth. OBJECTIVE: To investigate Internet access, use and acceptability as means for health promotion and health service delivery among HIV-positive youth. METHODS: A community-based participatory approach was used to conduct a mixed methods research study. Thirty-five qualitative in-depth semi-structured interviews were conducted with youth (ages 12-24) living with HIV in Ontario. Also, brief structured demographic surveys were administered at the time of the interview. A stakeholder group of youth living with HIV, professionals and researchers collaboratively analyzed the data for emerging themes. RESULTS: Five main themes were identified with respect to the youth's use of and interest in the Internet as a health promotion strategy. These include: (1) high rates of Internet use and access; (2) issues around public and private terminals; (3) their use of the Internet primarily for communication and entertainment; (4) the rarity of health information seeking behavior in this group; and (5) wanting "one-stop shopping" from an e-health site. HIV-positive youth were enthusiastic about the possibility of content that was developed specifically to target them and their needs. Also, they were keen about the possibilities for increased social support that youth-specific online chat rooms and message boards might provide. CONCLUSION: Given high rates of use, access and interest, the Internet provides an important way to reach young people living with HIV using health services and health promotion programs. The onus is on e-Health developers to understand the particular needs of HIV-positive youth and create relevant content.

Adolescent↗
PubMed1987

Fast kinetic method for methemoglobin developed and adapted for quantification of hemoglobin in whole blood.

We studied the kinetics of the reaction of cyanide with methemoglobin (mHb), used the information to develop a fast kinetic method for quantifying methemoglobin, then used that method to quantify hemoglobin (Hb) in whole blood based on the reaction with ferricyanide to produce mHb. Reaction conditions for mHb and cyanide are adjusted to give pseudo-first-order behavior with an apparent rate constant that increases linearly with cyanide concentration, decreases linearly with pH, and follows an Arrhenius-type relationship with temperature. Absorbance change, computed from kinetic data with a curve-fitting method, varies linearly with mHb concentration. Although the reactions are monitored most reliably with stopped-flow mixing, cyanide concentration was used to decrease reaction velocities to be compatible with centrifugal mixing. Kinetic results (y) for Hb in blood by both mixing methods correlate well with equilibrium results (x): y = 1.000x + 0.02 mmol/L, Syx = 0.06 mmol/L with stopped-flow mixing; y = 1.03x + 0.12 mmol/L, Syx = 0.07 mmol/L with centrifugal mixing; r = 0.96 and n = 21 in each case.

Ferricyanides↗
PubMed1998

Discrepancy between tau immunoreactivity and argyrophilia by the Bodian method in neocortical neurons of corticobasal degeneration.

To clarify different features of cytoskeletal pathology in neocortical neurons between corticobasal degeneration (CBD) and Alzheimer's disease (AD), the relationship between neurofibrillary tangles (NFTs), which are defined as a fibrillary structure stained by the Bodian method, and tau-immunopositive neurons in layers II-III of the premotor cortex was assessed by sequential staining for tau immunohistochemistry followed by the Bodian method on the same section. In AD brains, tau-like immunoreactivity in neurons was uniformly colocalized with Bodian-positive NFTs. In CBD brains, however, tau-immunopositive neurons could be classified into three different types: (1) those not stained at all by the Bodian method (diffuse cytoplasmic type), which represented the majority of these immunopositive neurons, (2) some partly stained by the Bodian method (mixed type), and (3) a few for which argyrophilia demonstrated by the Bodian method was completely colocalized with immunoreactivity (NFT type). This discrepancy between tau-like immunoreactivity and Bodian method is characteristic of CBD and suggests that the tau molecule is less liable to form argyrophilic fibrils in neocortical neurons of CBD.

Aged↗
PubMed2003

Mixing of acrylic bone cement: effect of oxygen on setting properties.

The present study investigates the effect of different mixing methods on the setting properties of bone cement. It was found that vacuum mixing decreased the setting time of the bone cement by nearly 2 min (10%), compared to mixing in air. Two additional experiments, in which the bone cement powders were purged with argon or oxygen, and mixed with the methyl methacrylate monomer, revealed that oxygen concentrations in the bone cement had a great effect on the setting time. The setting time increases significantly as the oxygen concentration increases, which suggests that the decrease in the setting time by vacuum mixing may be attributed to the lower oxygen levels present in the mixer. No significant effect was observed on dough time or maximum exothermic temperature by varying oxygen concentrations in the bone cement mixer.

Cementation↗
PubMedDate not supplied

Culture, black men, and prostate cancer: what is reality?

BACKGROUND: The worldwide incidence of prostate cancer is higher among American black men than any other male group. In the United States, lack of participation in screening for prostate cancer by black men is influenced by several cultural factors, including knowledge, health beliefs, barriers, and relationships with primary healthcare providers. METHODS: We used the qualitative and paralleling descriptive quantitative findings of a mixed-method longitudinal study exploring prostate cancer screening behaviors among 277 black men. RESULTS: Five themes were identified as critical elements affecting men's screening for prostate cancer: lack of knowledge, communication, social support, quality of care, and sexuality. These themes were associated with a sense of disconnectedness by black men from the healthcare system and contributed to nonparticipation in prostate cancer early detection activities. CONCLUSIONS: Lack of discussion about the decision to screen for prostate cancer and general lack of culturally appropriate communication with healthcare providers has engendered distrust, created fear, fostered disconnect, and increased the likelihood of nonparticipation in prostate cancer screening among black men.

Adult↗
PubMed2003

Influence of metallic chlorides on the formation of PCDD/Fs during low-temperature oxidation of carbon.

Experimental study was conducted to clarify the formation behavior of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) from carbonaceous materials through a de novo synthesis route. Samples were prepared by changing mixing method and composite state of metallic chloride in graphite powder in order to simulate the texture of "unburned carbonaceous particles", i.e., soot, formed in thermal processes. Reagents of KCl, CaCl2. 2H2O, FeCl3 x 6H2O, and CuCl2 x 2H2O were used as chlorine sources and were added to graphite powder with different methods. The composite state of metallic chloride was varied by preliminary treatments: hand-mixing, mixed-grinding using a high-intensity ball mill, and preheating at different temperatures between 500 and 1100 degrees C. In the de novo experiment, reaction temperature and oxygen concentration of flowed gas were set at 300 degrees C and 2.5 mol %, respectively. During the experiment, formation rates of CO and CO2 and the formed amounts of organic chlorine and PCDD/Fs were measured. The results show a reasonable relation between the amount of formed organic chlorine and oxidation rate of carbon, and the order of the activity of metallic chlorines was obtained as KCl < CaCl2 < FeCl3 << CuCl2. Furthermore, it was found that the effect of the composite state of metallic chloride on the formation of PCDD/Fs significantly depends on the kind of metal. The results will give useful information to examine the formation mechanism of PCDD/Fs from unburned carbon particles in thermal processes.

Benzofurans↗
PubMed2001

Triangulation using a meta-matrix.

BACKGROUND AND SIGNIFICANCE: Quantitative and qualitative data analysis are often undertaken as separate enterprises, as they emerge from differing philosophies of science and methodologies for data collection, management and analysis. Quantitative data analysis is sometimes seen in philosophic and methodologic conflict with a naturalistic, human science perspective of science. Researchers interested in data from both realms often rely on triangulation procedures, in which each is considered from its representative lens. Results are then projected out into a common area where data are melded and discussed. The purpose of this paper is to introduce the meta-matrix as a tool for triangulation in nursing research and to demonstrate its usefulness in an exemplar case. DESIGN/METHODS: The exploratory nature of a recent study led to the decision to manage triangulation using an emerging methodology, thereby allowing consideration of all data simultaneously through the use of a meta-matrix. Discussion of the meta-matrix as a method is presented. FINDINGS: Use of the meta-matrix facilitated data analysis and allowed pattern recognition across data sets. Discovery of several unexpected relationships deepened understanding of the results and assisted in identifying questions for further research. CONCLUSIONS/IMPLICATIONS: The meta-matrix method provides a useful alternative approach for secondary-level data analysis in mixed-methods research.

Data Interpretation, Statistical↗
PubMed2004

Developing lecturer practitioner roles using action research.

BACKGROUND: Lecturer Practitioner roles are well established in the United Kingdom. The national literature demonstrates that these staff are valuable to National Health Service trusts and universities however, their roles are busy and demanding, with conflicting expectations from the two employers. In addition, their role in addressing the theory-practice gap - a major reason for their establishment - is at best unclear. Although a number of qualitative studies have explored the topic, there have been no systematic attempts to develop the role or to quantify the effects on postholders. AIM: This paper reports a study that aimed to develop aspects of Lecturer Practitioners' work roles, examine the effects of this on individuals at one English university, and to quantify Lecturer Practitioners' occupational stress and burnout. METHODS: A flexible, 'spiral' action research framework and 'collaborative group approach' were used, with mixed methods of data collection. Data were collected through focus groups, meetings and participant feedback, and participants' reflective diaries. A questionnaire using previously validated psychological attitude rating scales was also used to measure occupational stress and burnout, the extent to which the project influenced these, and the influence of Lecturer Practitioners' experience and qualifications. Six null hypotheses were constructed to measure these ideas. Findings from qualitative and quantitative perspectives were triangulated to give depth to the analysis. FINDINGS: Five themes emerged from the focus groups: personal motivation, workload pressures, role clarity, preparation and support, and gains from the role. Specific policies and documentation were developed as a result of this initial project planning work. The findings from the questionnaire indicated that Lecturer Practitioners were no more stressed or burnt out than comparable workers. Synthesis of findings indicated, broadly speaking, that these LPs were 'thriving rather than just surviving'. CONCLUSION: Action research was an effective methodology for uncovering new knowledge, and bringing about organizational change in this project.

Burnout, Professional↗
PubMed1996

[Diabetes mellitus is currently one of the most frequent causes or associated causes of uremia. Data from the Piedmont registry of dialysis and transplantation (update, December 1993)].

A regular dialytic treatment of diabetic patients is until accepted from about twenty years in many areas. Aim of this work was a retrospective analysis of main clinical and survival data of diabetic patients (diabetic nephropathy or diabetes as comorbidous factor = 659 cases) admitted for dialysis in Piedmont (Northern Italy Region about 4,400,000 inhabitants) in the period 1981-1993 (functional recovery and follow-up < 1 month excluded). A progressive increment in incidence of diabetic patients was seen mostly in the aged. At 12/31/1993, 263 of 2404 patients admitted for dialysis were diabetics (10.9%); the majority of them was treated in Hospital Centers with bicarbonate haemodialysis (54.4%), while a small group was treated with CAPD (12.9%). During the years ¿80 was seen a progressive leaving of CAPD as first choice method in this population and in the last period the orienteering is the utilization of mixed methods (diffusive-convective as first choice). As regards the survival are not prominent significant differences between this cohort and the cohort affected by vasculopathy as comorbidous factor (86.2 and 54.2% in diabetics vs 78.6 and 55.2% in patients affected by vasculopathy at 1 and 3 years--p = 0.3481; patients aged 45-64 years). In conclusion the cohort of diabetic patients represent a good marker of the clinical problems of the elder population with high clinic risk, in progressive increasing in our Region.

Adult↗
PubMed2004

Lactobacillus GG effect in increasing IFN-gamma production in infants with cow's milk allergy.

BACKGROUND: Probiotic bacteria are potentially beneficial to maturation of the infant's immune system. OBJECTIVE: To examine the role of probiotic bacteria in treatment of cow's milk allergy (CMA) and IgE-associated dermatitis, we investigated the immunologic effects of Lactobacillus rhamnosus GG (LGG) and a mixture of 4 bacterial species (MIX). METHODS: In a randomized, double-blind study design, concomitantly with elimination diet and skin treatment, LGG, MIX, or placebo was given for 4 weeks to infants with suspected CMA. After anti-CD3 (OKT3) and anti-CD28 stimulation of PBMCs, IFN-gamma, IL-4, IL-5, and IL-12 levels were measured in culture supernatants by ELISA. Intracellular IFN-gamma, IL-4, and IL-5 production on CD4 lymphocytes was analyzed with fluorescence-activated cell sorting. RESULTS: Secretion of IFN-gamma by PBMCs before the treatment was significantly lower in infants with CMA (P=.016) and in infants with IgE-associated CMA (P=.003) than in non-CMA infants. Among the infants who received LGG, the level of secreted IFN-gamma increased in those with CMA (P=.006) and in those with IgE-associated dermatitis (P=.017) when compared with the placebo group. Secretion of IL-4 increased significantly in infants with CMA in the MIX (P=.034) but not in the LGG group. CONCLUSION: Deficiency in IFN-gamma response appears to be related to CMA. LGG raises IFN-gamma production of PBMC in infants with CMA and in infants with IgE-associated dermatitis and may thus provide beneficial TH1 immunomodulatory signals. MIX, although containing LGG, appears to modulate the immune responses differently.

Cytokines↗
PubMed2001

Scale, Efficiency and Organization in Norwegian Psychiatric Outpatient Clinics for Children.

BACKGROUND: It is generally believed that 5 percent of the population under 18 years is in need of specialist psychiatric care. In 1998, however, services were delivered to only 2.1 percent of the Norwegian population. Access to services can be improved by increasing capacity, but also by increasing the utilization of existing capacity. Changing financial incentives has so far not been considered. Based on a relatively low number of registered consultations per therapist (1.1 per therapist day) the ministry has stipulated that productivity should increase by as much as 50 percent. AIMS OF THE STUDY: Measuring productivity in psychiatric care is difficult, but we believe that studies of productivity should be an important input in policy making. The aim of this paper is to provide such an analysis of the productive efficiency of psychiatric outpatient clinics for children and youths, and in particular to focus on three issues: (i) is an increase in productivity of 50 percent a realistic goal, (ii) are there economies of scale in the sector, and (iii) to what extent can differences in productivity be explained by differences in staff-mix and patient-mix? METHODS: We utilize an approach termed Data Envelopment Analysis (DEA) to estimate a best-practice production frontier. The potential for efficiency improvement is measured as the difference between actual and best-practice performance, while allowing for trade-offs between different staff groups and different mixes of service production. The DEA method gives estimates of efficiency and productivity for each clinic without the need for prices, and thus avoids the pitfalls of partial productivity ratios. The Kolmogorov-Smirnov statistic is used to compare efficiency distributions, providing tests of variable specification and scale properties. RESULTS: Based on 135 observations for the years 1997 to 1999, the tests lead to a model with two inputs, two outputs and variable returns to scale. The outputs are number of hours spent on direct and indirect interventions, while neither the number of interventions nor the number of patients was found to be significant. The inputs are the number of university-educated staff and other staff, but disaggregation of the latter group was not significant. The average of estimated clinic efficiencies is 71%. The mean productivity is 64%, but many large clinics have considerably lower performance due mainly to scale inefficiency. DISCUSSION: There seems to be considerable room for improved performance in these clinics. It is interesting that the potential is not that far from the officially stipulated goal of 50% increased productivity. Staff composition does matter for clinic performance, but the different groups do not have significantly different marginal productivities, indicating a lack of ability to utilize specialized skills. It should be noted that these results to some extent depend on the assumptions that medical practice is efficient, and that the available data accurately captures the activities of the clinics. IMPLICATIONS FOR FURTHER RESEARCH AND HEALTH POLICY: More appropriate outcome measures, e.g. global assessment of functioning scores (GAF), will soon be available and will improve the policy value of this type of analysis, as will a more refined data set with information about the number of personnel in training positions. The analyses in this paper indicate that a lack of consensus on the issues of who should be treated, how they should be treated and by whom results in large variations in productive efficiency. These issues are being debated in Norway, and it should be interesting to see whether this in itself leads to higher efficiency or whether a change in the incentive structure will be needed.

Journal Article↗
PubMed2003

A universal method for determining intensive care unit bed requirements.

OBJECTIVE: Most methods used to estimate ICU bed needs rely either on simple formulas that do not consider the actual needs of the population or on simulations that are too specific to be applicable to all hospitals. We sought to develop a universally applicable nonparametric method. DESIGN AND SETTING: For each day, the number of immediate patient transfers to other ICUs because of a full unit and the number of patients treated in the ICU were collected. The number of beds needed was selected according to the minimization of both the mean and the variance of three parameters (accessibility, safety, and efficiency). This method was applied to the ICU of a general hospital. Robustness of the model was assessed using outliers. MAIN RESULTS: During the 5-month study period, 215 ICU stays were collected. The method selected a ten-bed model whereas length-of-stay ratio and case-mix methods selected a twelve- and height-bed models respectively. An unusual increase in admission requests had no consequence on the bed number selected, indicating that the method was robust. None of the parameters were dependent on specific ICU characteristics, establishing that this method is applicable to any type of hospital ward. CONCLUSION: Our model is reliable for determining the number of beds needed in any type of ICU and can be used by all ICU managers. The software is available.

Beds↗
PubMed1968

Time dependence of activation of muscle AMP-aminohydrolase by substrate and potassium ion.

The kinetics of AMP-aminohydrolase, which under steady state conditions shows a typical sigmoid dependence of initial velocities versus substrate concentration, have been examined by rapid mixing methods. Using this technique it was observed that when substrate or substrate plus activator (K(+)) were mixed with enzyme, the rate of appearance of product markedly increased during the first few tenths of a second. The time course of this change in rate was taken to reflect the progress of activation by substrate or by K(+). On the other hand, addition of activator to enzyme prior to mixing with substrate gave process curves for the formation of product consistent with normal Michaelis-Menten behaviour.Under the conditions where the reaction was examined, the enzyme at time zero had less than 10% of the activity of the fully active enzyme. The time course for activation with K(+) followed a first order process with a rate constant of 10.6 sec(-1) at 20 degrees C. A simple mechanism consistent with the data and capable of explaining the sigmoid dependence of initial velocities versus substrate concentrations observed in steady state kinetics was proposed.

Journal Article↗
PubMed2006

A systematic review of faculty development initiatives designed to improve teaching effectiveness in medical education: BEME Guide No. 8.

BACKGROUND: Preparing healthcare professionals for teaching is regarded as essential to enhancing teaching effectiveness. Although many reports describe various faculty development interventions, there is a paucity of research demonstrating their effectiveness. OBJECTIVE: To synthesize the existing evidence that addresses the question: "What are the effects of faculty development interventions on the knowledge, attitudes and skills of teachers in medical education, and on the institutions in which they work?" METHODS: The search, covering the period 1980-2002, included three databases (Medline, ERIC and EMBASE) and used the keywords: staff development; in-service training; medical faculty; faculty training/development; continuing medical education. Manual searches were also conducted. Articles with a focus on faculty development to improve teaching effectiveness, targeting basic and clinical scientists, were reviewed. All study designs that included outcome data beyond participant satisfaction were accepted. From an initial 2777 abstracts, 53 papers met the review criteria. Data were extracted by six coders, using the standardized BEME coding sheet, adapted for our use. Two reviewers coded each study and coding differences were resolved through discussion. Data were synthesized using Kirkpatrick's four levels of educational outcomes. Findings were grouped by type of intervention and described according to levels of outcome. In addition, 8 high-quality studies were analysed in a 'focused picture'. RESULTS: The majority of the interventions targeted practicing clinicians. All of the reports focused on teaching improvement and the interventions included workshops, seminar series, short courses, longitudinal programs and 'other interventions'. The study designs included 6 randomized controlled trials and 47 quasi-experimental studies, of which 31 used a pre-test-post-test design. KEY POINTS: Despite methodological limitations, the faculty development literature tends to support the following outcomes: Overall satisfaction with faculty development programs was high. Participants consistently found programs acceptable, useful and relevant to their objectives. Participants reported positive changes in attitudes toward faculty development and teaching. Participants reported increased knowledge of educational principles and gains in teaching skills. Where formal tests of knowledge were used, significant gains were shown. Changes in teaching behavior were consistently reported by participants and were also detected by students. Changes in organizational practice and student learning were not frequently investigated. However, reported changes included greater educational involvement and establishment of collegiate networks. Key features of effective faculty development contributing to effectiveness included the use of experiential learning, provision of feedback, effective peer and colleague relationships, well-designed interventions following principles of teaching and learning, and the use of a diversity of educational methods within single interventions. Methodological issues: More rigorous designs and a greater use of qualitative and mixed methods are needed to capture the complexity of the interventions. Newer methods of performance-based assessment, utilizing diverse data sources, should be explored, and reliable and valid outcome measures should be developed. The maintenance of change over time should also be considered, as should process-oriented studies comparing different faculty development strategies. CONCLUSIONS: Faculty development activities appear highly valued by participants, who also report changes in learning and behavior. Notwithstanding the methodological limitations in the literature, certain program characteristics appear to be consistently associated with effectiveness. Further research to explore these associations and document outcomes, at the individual and organizational level, is required.

Cooperative Behavior↗
PubMed2003

Apoptosis, proliferation, and hormone receptors in endometrial carcinoma: results depending on methods of analysis.

Apoptosis and proliferation were studied in 29 endometrial adenocarcinomas of the endometrioid type and characterized by the immunohisto-chemical pattern of estrogen receptor (ER) alpha and progesterone receptor (PR) expression. Intratumoral heterogeneous distribution of both ER and PR as well as of the proliferation marker Ki-67 was studied and quantified. Both density and heterogeneity of the two steroid receptors and Ki-67 varied, depending on the histological malignancy grade (grades 1-3, or G1-3); interestingly, however, the apoptotic index (Ai) was in the same range for all grades. Receptor staining was evaluated by three different methods: i) counting the percentage of stained cells (staining index), according to stereological principles; ii) the mixed method, a combination of the staining index results and ranking staining intensity; and iii) a superficial and rapid visual scoring. The three methods gave equal results. Apoptotic cells and bodies were generally scattered in the endometrial carcinoma but more frequently observed adjacent to necrotic foci. Bcl-2, known as anti-apoptotic factor, showed no correlation to apoptotic index, Ki-67 expression, ER, or PR. Overexpression of p53 was seen in two tumors of grade 3. In a detailed study of intra-tumoral microfoci performed on consecutively taken tissue sections, a higher staining index of both ER and PR was found in the areas of maximal proliferation compared with the areas of minimal proliferation in tumors of grades 1-2, but not in G3 tumors. Other covariations were also found when non-specified areas were studied. The Ki-67 index was both higher and more heterogeneous in G2-3 tumors than in G1 tumors. Our results indicate that there is an increasing discrepancy between cell death and cell proliferation with progressing tumor grade, which may contribute to the differences in tumor aggressivity.

Apoptosis↗
PubMed1992

Fluctuation in mixed venous oxygen saturation in critically ill medical patients: a pilot study.

OBJECTIVE: To determine fluctuation in mixed venous oxygen saturation in critically ill medical patients during a period of rest. DESIGN: Nonexperimental, descriptive. SETTING: The medical and coronary intensive care units in a large county hospital in south-central Texas. PATIENTS: Twenty critically ill patients, aged 19 to 85, who had placement of a pulmonary artery catheter capable of continuous monitoring of mixed venous oxygen saturation. The majority had a diagnosis of respiratory failure and required mechanical ventilation. METHODS: Mixed venous oxygen saturation was recorded each minute for a 2-hour period in either early morning or late afternoon hours. Minute-by-minute values obtained during a 30-minute period of rest were used to determine fluctuation. The lowest and highest mixed venous oxygen saturation values during the period were used to calculate percent changes from average values (fluctuation). RESULTS: The range of fluctuation was +/- 6% of the average mixed venous oxygen saturation value for 80% of the sample. Four patients had a greater range of fluctuation: however, their actual mixed venous oxygen saturation values were within a clinically acceptable range. No significant differences in percentage of low or high fluctuation were noted for the following variables: time of day, medication administration, oxygen delivery, oxygen consumption and average mixed venous oxygen saturation. The percentage of low fluctuation was significantly lower for four patients who were not mechanically ventilated. CONCLUSIONS: Knowledge of normal fluctuation enables the care giver to evaluate changes in mixed venous oxygen saturation in response to activities and/or treatments. Additional study of fluctuation in homogenous groups of critically ill patients is warranted.

Adult↗
PubMed1998

Evidence for barrier-limited protein folding kinetics on the microsecond time scale.

Although important structural events in protein folding are known to occur on the submillisecond time scale, the limited time resolution of conventional kinetic methods has precluded direct observation of the initial collapse of the polypeptide chain. A continuous-flow capillary mixing method recently developed by us made it possible to account for the entire fluorescence change associated with refolding of cytochrome c from approximately 5-10(-5)-10(2) s, including the previously unresolved quenching of Trp 59 fluorescence (burst phase) indicative of the formation of compact states. The kinetics of folding exhibits a major exponential process with a time constant of approximately 50 micros, independent of initial conditions and heme ligation state, indicating that a common free energy barrier is encountered during the initial collapse of the polypeptide chain. The resulting loosely packed intermediate accumulates prior to the rate-limiting formation of specific tertiary interactions, confirming previous indications that folding involves at least two distinct stages.

Animals↗