Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases.

BACKGROUND: An accurate, sensitive, but brief quality-of-life outcomes measure is needed for studies of dermatologic care. OBJECTIVE: To construct a single-page version of Skindex (a dermatologic quality-of-life instrument) that would have two new features compared with the current 29-item version: (1) fewer items to which a majority of patients choose the same response, and (2) measurement of bother rather than frequency of patient experiences. METHODS: Random samples of patients waiting for dermatology appointments in clinics of Veterans Affairs hospitals and in private dermatology practices completed questionnaires; 692 patients responded to the parent instrument and 541 additional patients responded to the brief version. Reproducibility, internal consistency reliability, validity, and responsiveness of the brief version of Skindex were determined. RESULTS: For 16 items of the current 29-item version (55%), more than 50% of patients responded "Never." After an explicit process of item analysis and elimination, a single-page 16-item version was composed that asks patients about bother from their experiences; responses are reported as three scales, Symptoms, Emotions, and Functioning. For 6 items of the 16-item version (38%), more than 50% of patients responded "Never." Scale scores were reproducible after 72 hours (r = 0.88-0.90) and were internally reliable (Cronbach's alpha = 0.86-0.93). The instrument demonstrated both content and construct validity: Most patients' responses to an open-ended question about their skin disease was addressed by the items; patients with inflammatory dermatoses had higher scores than those with isolated lesions; and in an exploratory principal axes factor analysis with an oblique rotation, 74% of the common variance was explained by three factors that correlated with the a priori scales. Mean scale scores stayed the same or changed in the expected direction in patients who reported that their skin was the same or had improved. CONCLUSION: This brief single-page version of Skindex accurately and sensitively measures how much patients are bothered by their skin conditions.

When doctors marry doctors: a survey exploring the professional and family lives of young physicians.

BACKGROUND: Soon, half of all physicians may be married to other physicians (that is, in dual-doctor families). Little is known about how marriage to another physician affects physicians themselves. OBJECTIVE: To learn how physicians in dual-doctor families differ from other physicians in their professional and family lives and in their perceptions of career and family. DESIGN: Cross-sectional survey. SETTING: Two medical schools in Ohio. PARTICIPANTS: A random sample of physicians from the classes of 1980 to 1990. MEASUREMENTS: Responses to a questionnaire on hours worked, income, number of children, child-rearing arrangements, and perceptions about work and family. RESULTS: Of 2000 eligible physicians, 1208 responded (752 men and 456 women). Twenty-two percent of male physicians and 44% of female physicians were married to physicians (P < 0.001). Men and women in dual-doctor families differed (P < 0.001) from other married physicians in key aspects of their professional and family lives: They earned less money, less often felt that their career took precedence over their spouse's career, and more often played a major role in child-rearing. These differences were greater for female physicians than for male physicians. Men and women in dual-doctor families were similar to other physicians in the frequency with which they achieved career goals and goals for their children and with which they felt conflict between professional and family roles. Marriage to another physician had distinct benefits (P < 0.001) for both men and women, including more frequent enjoyment from shared work interests and higher family incomes. CONCLUSIONS: Men and women in dual-doctor families differed from other physicians in many aspects of their professional and family lives, but they achieved their career and family goals as frequently. These differences reflect personal choices that will increasingly affect the profession as more physicians marry physicians.

Reports by patients and dermatologists of skin cancer preventive services provided in dermatology offices.

OBJECTIVE: To learn how often patients receive skin cancer preventive services in dermatologists' offices. DESIGN: Survey of dermatology patients and dermatologists. SETTING: Dermatology practices of full-and part-time faculty at a midwestern medical school. PARTICIPANTS: Patients were randomly selected from clinical sessions of 11 dermatologists. Of 200 patients enrolled, 162 (81%) responded to the survey. Ten (91%) of the dermatologists responded, and 4 additional dermatologists from the faculty were also surveyed. MAIN OUTCOME MEASURES: Patients' and dermatologists' reports of the provision of skin cancer prevention counseling and screening for skin cancer. RESULTS: Most patients (93%) had been informed about the risks of sun exposure, but for only 27% was a dermatologist the main source of information. Although 76% of patients had seen a dermatologist at least twice in the last 5 years, only 34% reported that they had ever received a total-body screening examination for skin cancer. Most patients (55%) would like to learn more about skin cancer prevention, and responded that they would learn best from a brochure (43%) or from a dermatologist (42%). All dermatologists believed that some skin cancer preventive services should be provided to each patient, but they varied widely in the proportion of their white adult patients to whom they provided such services. For example, with respect to counseling about sunscreens, the same number of dermatologists (4 [29%]) responded that they counsel 25% or less of their patients, and more than 75% of their patients. CONCLUSION: There is wide variation in how often skin cancer preventive services are provided in dermatologists' offices.

Acne vulgaris and the quality of life of adult dermatology patients.

OBJECTIVE: To determine the effects of acne vulgaris on the quality of life of adult dermatology patients. DESIGN: Cross-sectional and longitudinal questionnaire study. PATIENTS: Sixty patients with acne vulgaris attending appointments with their dermatologists. MAIN OUTCOME MEASURES: Findings using Skindex, a validated 29-item instrument to measure the effects of skin disease on patients' quality of life. Results are reported as 3 scale scores (functioning, emotions, and symptoms) and a composite score (average scale score). In addition, dermatologists rated the clinical severity of patients' skin disease, and patients responded to a global question about how they are bothered by acne. Higher Skindex scores indicate greater effects on quality of life. RESULTS: Patients with acne experienced functioning and emotional effects from their skin disease comparable with those of patients with psoriasis, but experienced fewer symptoms (for patients with acne and psoriasis, respectively, Skindex functioning scores of 14.9 and 22.8 [P=.08]; emotion scores, 39.2 and 38.9 [P=.95]; and symptoms scores, 29.5 and 42.1 [P<.05]). Skindex scores were higher in older patients than in younger patients, and patients aged 40 years or older were less likely to report improvement in their acne after 3 months (43% vs 85%; P<.05). Among patients reporting no improvement in their acne, older patients reported greater effects of their acne on their quality of life. Furthermore, in multivariate analyses, older adults reported more effects of acne on their quality of life than younger adults, even after controlling for sex and acne severity as judged by the dermatologist. CONCLUSIONS: Acne vulgaris significantly affects patients' quality of life. Regardless of the severity of acne, older adults were more affected by their acne.

What patients should ask of consumers' guides to health care quality.

Consumers' guides that profile the quality of care of individual health care providers may be influential in shaping health care markets. We propose four simple questions that can be used to evaluate such guides: (a) Does the guide measure distinct and important domains of health care quality? (b) Are the individual measures of quality described simply and precisely? (c) Do the measures take into account relevant differences between patients? (d) Are the ratings of quality presented fairly? Using these four questions, we examine the validity of one prominent guide that annually identifies America's best hospitals and present a set of recommendations for the design of future guides. Although the evaluation of health care quality is undoubtedly complex, the four questions that we pose provide a basis for developing a more rational approach to informing the public about health care quality.

Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases.

OBJECTIVE: To improve Skindex, a dermatologic quality-of-life instrument. DESIGN: Cross-sectional and longitudinal questionnaire study. SETTING: Dermatology clinic of a Veterans Affairs hospital and private dermatology practices. PATIENTS: Patients waiting for dermatology appointments; 201 patients responded to the original version of Skindex and 692 additional patients to the revised version. MAIN OUTCOME MEASURES: Reproducibility, internal consistency reliability, and validity of the revised version of Skindex. The revised version was compared with the original in 3 ways: the amount of time patients need to complete it; discriminative capability, determined as the number of items to which patients chose the same response; and evaluative capability, determined as the number of scales that were responsive to patients' reports of clinical change. RESULTS: With the revised 29-item version of Skindex, scale scores were reproducible after 72 hours (r = 0.88-0.92) and were internally reliable (Cronbach alpha = 0.87-0.96). The instrument demonstrated both construct and content validity; patients with psoriasis and eczema responded with higher scores than those with isolated lesions; in an exploratory principal axes factor analysis with an oblique rotation, 97% of the common variance was explained by 3 factors that correlated with the a priori scales; and most patients' responses to an open-ended question about their skin disease were addressed by items in the instrument. The average time to complete the revised instrument was 5 minutes (compared with 15 minutes for the original version). For only 3 items (10%) did 70% or more of patients choose the same response (vs 17 [28%] of items in the original version). All scales changed significantly in the expected direction in patients who reported that their skin had changed after 3 months (vs only 3 of 8 scales originally). CONCLUSION: The 29-item version of Skindex remains reliable and valid, but has decreased respondent burden and improved discriminative and evaluative capability.

Convergent and discriminant validity of a generic and a disease-specific instrument to measure quality of life in patients with skin disease.

Skindex is a quality-of-life instrument for skin diseases. To determine its convergent validity and its advantage relative to a generic measure, we compared responses of 132 dermatology patients to Skindex and the Medical Outcomes Study 36-item Short-Form Survey (SF-36). We hypothesized that (i) correlations between similar scales would be strong but not redundant (r = 0.5-0.6), and (ii) Skindex scores would correlate more highly with responses about skin disease-related aspects of health, and SF-36 scores would correlate more highly with responses concerning general health. As measured by the SF-36, patients reported general health status similar to the normal population, and SF-36 scores did not correlate with dermatologists' judgments about the severity of skin disease. Correlations between the same scales of the two instruments were as hypothesized (range of r, 0.44-0.56), and patients with low, medium, or high responses to Skindex differed similarly in SF-36 scores. On the other hand, some patients who reported on the SF-36 that they were free of physical symptoms (37% of patients) or social effects (54%) on Skindex, reported such effects from their skin disease. Also, responses about skin-related health aspects correlated more highly with Skindex than SF-36 (for skin condition, mean r = 0.42 vs 0.28; for disfigurement, 0.38 vs 0.24). Conversely, responses concerning general health correlated more highly with SF-36 than Skindex (for self-reported health status, mean r = 0.28 vs 0.16; for co-morbidity, 0.48 vs 0.37). This study further supports the validity of Skindex and also suggests that both generic and disease-specific health status measures can contribute to the assessment of patients with skin diseases.

Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness.

To measure the effects of skin disease on patients' quality of life, we developed a 61-item self-administered survey instrument called Skindex. Skindex has eight scales, each of which addresses a construct, or an abstract component, in a comprehensive conceptual framework: cognitive effects, social effects, depression, fear, embarrassment, anger, physical discomfort, and physical limitations. Item responses are standardized from 0 (no effect) to 100 (maximal effect); a scale score is the average of responses to items addressing a construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD) ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was assessed in two ways: (i) in a comparison of patients with inflammatory dermatoses and patients with isolated lesions, patients with inflammatory dermatoses had higher scale scores, and (ii) in an exploratory factor analysis, 78% of the common variance was explained by seven factors that correlated with the scale scores of Skindex. Most of the a priori scale scores changed in the expected direction in patients who reported that their skin conditions had improved or worsened after 6 mo. Finally, physicians' judgments of disease severity did not consistently correlate with Skindex scores. These preliminary data suggest that Skindex reliably and responsively measures the effects of skin disease on patients' quality of life and may supplement clinical judgments of disease severity.

The annual guide to "America's best hospitals". Evidence of influence among health care leaders.

To determine health care leaders' opinions about a prominent guide to hospital quality, we surveyed 82 chief executive officers (CEOs) and 80 chiefs of staff of hospitals listed in the 1994 edition of the guide and 50 directors of employer based coalitions. Most of the CEOs (87%) and chiefs of staff (86%) said the guide was used in advertising. More than three quarters of the CEOs, chiefs of staff, and coalition directors who were familiar with the guide thought it was accurate, and most indicated that key constituencies (e.g., physicians, corporate managers) were aware of the guide. Our results demonstrate the likely influence of one prominent guide to health care quality and highlight the need for formal independent assessment of such guides.

Polylysine cross-links axoplasmic neurofilaments into tight bundles.

We have used axoplasm from the squid giant axon to investigate the effects of anionic and cationic polypeptides on the mobility and organization of axonal neurofilaments (NFs). Intact cylinders of axoplasm were extruded from squid giant axons into an excess volume of artificial axoplasm solution. In a previous study on the mobility of NFs in extruded axoplasm, we showed that these polymers disperse freely and diffusively into the surrounding solution, thereby expanding the axoplasmic cross-sectional area [Brown and Lasek, 1993: Cell Motil. Cytoskeleton 26:313-324]. In the present study, we found that 83nm-long ("long-chain") polylysine, a synthetic multivalent cationic protein, inhibited the radial expansion of isolated axoplasm and condensed the axoplasm, thereby reducing the cross-sectional area. Equivalent concentrations of a 7nm-long ("short-chain") polylysine did not inhibit the expansion of axoplasm by long-chain polylysine was dependent on the polylysine concentration; condensation of axoplasm was observed at concentrations of 0.01 mg/ml (0.27 microM) or greater. Electron microscopy of the condensed axoplasm showed that the NFs were aligned side-by-side and in parallel in closely-packed bundles. Equivalent concentrations of 91 nm-long ("long-chain") polyglutamate, a synthetic multivalent anionic protein, partially inhibited the expansion of axoplasm but did not cause the NFs to bundle and did not cause the axoplasm to condense. These studies indicate that cationic proteins bind tightly to the highly charged anionic surfaces of NFs and can link them together into compact bundles in a charge-dependent and length-dependent manner. The tightly packed organization of these cross-linked NFs differs from the normal loose organization of NFs in healthy axons. However, tightly bundled NFs are sometimes found in certain neuropathologies, such as giant axonal neuropathy.

The maximum rate of neurofilament transport in axons: a view of molecular transport mechanisms continuously engaged.

Neurofilaments (NFs) were radiolabeled in the optic systems of mice. The leading edge of the radiolabeled NF waveform was distinguished near the injection site (the eye) both by liquid scintillation spectroscopy and visually from fluorographs. The fastest NFs were found to be translocated at rates of between 72 and 144 mm/day. It appears that the continuous (maximal) operation of the slow axonal transport machinery can move polymers intra-axonally at rates one hundred times greater than those previously reported.

Neurofilaments assume a less random architecture at nodes and in other regions of axonal compression.

Neurofilament distributions were mathematically characterized in four chicken somatic motor axons at each of four histologically distinct regions: compact myelinated regions, compact myelinated regions associated with Schwann cell nuclei, Schmidt-Lanterman clefts, and nodes of Ranvier. Compact myelinated regions had the largest cross-sectional areas, the lowest neurofilament densities, and the most random neurofilament organizations--nodes of Ranvier had the smallest cross-sectional areas, the highest neurofilament densities, and the most ordered architectures. In these myelinated axons, the closest natural neurofilament spacing was 25 nm. Mathematical analyses of serial sections suggested that neurofilament interactions are sufficiently weak and transient to permit a full range of variation from random to ordered cytoskeletal architectures as the neurofilaments move longitudinally through the few micron span of the paranodal-nodal region of a single axon.

Neurofilaments move apart freely when released from the circumferential constraint of the axonal plasma membrane.

Squid giant axons were used to obtain axonal cytoskeletons that had been separated from the confines of their plasma membranes. To remove the plasma membrane, axoplasm was extruded from the giant axon directly into an artificial axoplasm solution (AAS). This procedure produces a smooth axoplasmic cylinder in which neurofilaments (NFs) are the most prevalent cytological elements. The NFs scatter light strongly and thus dark-field light microscopy can be used to quantify the volume occupied by these polymers. Measurements of the widths of the dark-field images of the axoplasmic cylinders showed that the cross-sectional area of the NF population increased by 60-110% (n = 8) between 1-100 min after plasma membrane removal, and then continued to increase more slowly for many hours. After 1,000 min, the cross-sectional area was 75-160% (n = 8) larger than at 1 min. These light microscopic measurements of axoplasm suggest that the NF population disperses to occupy a continuously increasing volume after removal of the plasma membrane and immersion in AAS. This inference was confirmed by quantitative ultrastructural studies of NFs in axoplasmic cross-sections, which demonstrated that the spacing between the NFs increased between 1-1,000 min after plasma membrane removal. Comparison of the NF density distribution after 1,000 min with a theoretical distribution calculated using the Poisson theorem indicated that the NFs dispersed randomly. These studies on NFs in isolated axoplasm suggest that ordinary thermal forces of Brownian motion are sufficient to move axonal NFs apart independently and thereby to disperse them. We propose that, in the intact axon, the dispersive movements of the NFs spread the NF cytoskeleton radially and expansively to fill out the cylindrical space contained by the axonal plasma membrane and its surrounding connective tissue elements.

Slow axonal transport mechanisms move neurofilaments relentlessly in mouse optic axons.

Pulse-labeling studies of slow axonal transport in many kinds of axons (spinal motor, sensory ganglion, oculomotor, hypoglossal, and olfactory) have led to the inference that axonal transport mechanisms move neurofilaments (NFs) unidirectionally as a single continuous kinetic population with a diversity of individual transport rates. One study in mouse optic axons (Nixon, R. A., and K. B. Logvinenko. 1986. J. Cell Biol. 102:647-659) has given rise to the different suggestion that a significant and distinct population of NFs may be entirely stationary within axons. In mouse optic axons, there are relatively few NFs and the NF proteins are more lightly labeled than other slowly transported slow component b (SCb) proteins (which, however, move faster than the NFs); thus, in mouse optic axons, the radiolabel of some of these faster-moving SCb proteins may confuse NF protein analyses that use one dimensional (1-D) SDS-PAGE, which separates proteins by size only. To test this possibility, we used a 2-mm "window" (at 3-5 mm from the posterior of the eye) to compare NF kinetics obtained by 1-D SDS-PAGE and by the higher resolution two-dimensional (2-D) isoelectric focusing/SDS-PAGE, which separates proteins both by their net charge and by their size. We found that 1-D SDS-PAGE is insufficient for definitive NF kinetics in the mouse optic system. By contrast, 2-D SDS-PAGE provides essentially pure NF kinetics, and these indicate that in the NF-poor mouse optic axons, most NFs advance as they do in other, NF-rich axons. In mice, greater than 97% of the radiolabeled NFs were distributed in a unimodal wave that moved at a continuum of rates, between 3.0 and 0.3 mm/d, and less than 0.1% of the NF population traveled at the very slowest rates of less than 0.005 mm/d. These results are inconsistent with the proposal (Nixon and Logvinenko, 1986) that 32% of the transported NFs remain within optic axons in an entirely stationary state. As has been found in other axons, the axonal transport system of mouse optic axons moves NFs and other cytoskeletal elements relentlessly from the cell body to the axon tip.

Microtubules have special physical associations with smooth endoplasmic reticula and mitochondria in axons.

Ultrastructural morphometry was used to document the non-random spatial distributions of organelles within the compact myelinated region of avian oculomotor axons. These regions contain large numbers of loosely packed neurofilaments (NFs) (241/microns 2) and only a relatively small number of microtubules (MTs) (4/microns 2), mitochondria (0.6/microns 2), and smooth endoplasmic reticulum (SER) (1.6/microns 2). Random co-occurrences between the relatively sparsely distributed MTs, mitochondria, and SER are probably infrequent in these axons. The actual co-occurrences of MTs, mitochondria, and SER with MTs were counted and compared to the co-occurrences expected in a random Poisson distribution. At long distances (200 nm), the co-occurrences were random. At shorter distances (40 nm and less), MTs were still randomly associated with other MTs. However, at these shorter distances, the spatial associations of mitochondria with MTs and of SER with MTs were not random; such preferential stable associations may be produced by specific MT associated cross-bridging proteins. In axons, MTs tend to be clustered together, giving the appearance of MT bundles. We propose that the MT-MT bundling is an indirect result of MT concentration along the continuous intra-axonal SER network, to which the MTs are apparently tied directly by dynamic molecular cross-bridges.

Internal axonal cytoarchitecture is shaped locally by external compressive forces.

The cross-sectional architecture of the axon and the area of its surrounding Schwann cell were quantified at selected histological regions along the length of avian myelinated axons. The number of neurofilaments (NFs), the density of NFs, axoplasmic area, and Schwann cell cross-sectional area were measured. These parameters were examined at Schmidt-Lanterman (S-L) clefts, at paranodal-nodal regions, and at regions of compact myelin Schwann cell nuclei. The results were then compared with the same parameters in adjacent compact myelinated regions of the same axons. At S-L clefts, paranodal-nodal regions, and Schwann cell nuclei, the axonal areas were smaller and the NF densities were higher than at compact myelinated regions. From other studies, it has been suggested that NF organization is responsive to local compressive forces--NF packing density tends to increase with increasing compression of the axon. We found that the NF packing densities were relatively small and the axon diameters were relatively large in the compact myelinated regions; this result suggests that in these axonal regions external constraints on axonal architecture are minimal. The higher NF packing densities and smaller axon diameters in the other histological regions suggest that external compressive effects on the axon increase in the following order: simple compact myelin less than Schwann cell nucleus less than S-L cleft less than paranodal-nodal region. Ultrastructural comparisons of these 4 histological regions show that the Schwann cell cross-sectional areas differ reproducibly, and this is consistent with the idea that variations in the organization of extra-axonal elements that envelop the axon produce different amounts of physical constraint on the axon and that this can affect the amount of external pressure on the internal architecture of the axon.

Cytomatrix protein residence times differ significantly between the tract and the terminal segments of optic axons.

The window method of radiolabeled protein analysis was used to study the transport kinetics of axonally transported cytomatrix proteins as they move through segments of mouse optic axons. Three slow component b (SCb) proteins--actin, a 30 kDa protein, and clathrin--were radiolabeled in the eye and were followed for up to 119 days by quantitative one-dimensional gel electrophoresis. These proteins appeared first in the optic nerve, next in the tract, and last in the superior colliculus. All of the radiolabeled proteins had passed through the optic axons and had been effectively removed from the terminals by 119 days. Two different axonal segments ('windows') were examined in detail: a segment of the axon shaft region in the optic tract, and a segment of axon terminal region in the midbrain superior colliculus. The median transit times of the 3 proteins were 53-100% longer in the colliculus than in the tract, and the pulse transients (the total area under the transport curve in each window) were 180-350% larger in the colliculus than in the tract. These results indicate that at least certain cytomatrix and cytoskeletal proteins have longer residence times in the terminal regions than in the axon proper.

Slow component B protein kinetics in optic nerve and tract windows.

The transport kinetics of 3 radiolabeled slow component b (SCb) proteins (a 30 kDa protein, clathrin, and actin) were examined in the axons of mouse retinal ganglion cells. To view the transit of these proteins through the entire optic pathway between the eye and the target cells, we used two different windows: (1) a 2 mm segment from the optic nerve located 3-5 mm from the eye, and (2) a 2 mm segment from the optic tract located past the chiasm 6-8 mm from the eye. The radiolabeled proteins from these windows were separated by 1- and 2-dimensional SDS-PAGE, and the individual radiolabeled bands were quantified. Radiolabeled proteins entered and cleared the optic axons between 1 and 119 days post-labeling. All these proteins had broader transport waves in the more distal optic tract window than in the more proximal optic nerve window. The spreading of transport waves as they advance along the axon appears to be produced by a playing out of the natural heterogeneity of axonal transport rates within each population of labeled proteins. Our results confirm the proposals that clathrin and the 30 kDa protein are transported principally with SCb and that actin is transported both with SCb and with SCa. Although these proteins can be generally classified with SCb, their detailed kinetics differed (for example, their median transit times differed) and, in summary, their characteristic rates of movement can be ordered as: clathrin greater than 30 kDa protein greater than actin.(ABSTRACT TRUNCATED AT 250 WORDS)

Retardation in the slow axonal transport of cytoskeletal elements during maturation and aging.

Using the pulse-labeling method, the rate of the slow component (SC) of axonal transport was analyzed during maturation and aging. Ventral motor neurons and retinal ganglion cells of 3-, 6-, and 24-month-old Fischer 344 rats were radiolabeled with 35S-methionine. To measure the rates of SCa and SCb subcomponents, distributions of the total radiolabeled proteins and certain cytoskeletal proteins (actin, clathrin, tubulin, and the neurofilament proteins) were analyzed in the ventral root-sciatic nerve and optic nerve. Our results show that the rate of transport for both SCa and SCb proteins decreases with age in ventral motor axons and optic axons. For example, in ventral motor axons the rates of both SCa and SCb decreased 40% between 6 and 24 months. These results, with those of others, show that the rate of slow transport gradually decreases in the neurons of adult rats (7,11) The factors that may contribute to the slowing are discussed.