Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA.

BACKGROUND: Vitiligo, an autoimmune disorder characterised by skin depigmentation, is associated with reduced quality of life (QoL). Vitiligo may be under-reported, in part because of misconceptions that it is a cosmetic disease. OBJECTIVES: This survey sought to characterise vitiligo prevalence and explore the relationship between sociodemographic and clinical characteristics with QoL in a population-based, multinational study. METHODS: Participants aged ≥18 years were recruited via an online panel in Europe, Japan and the USA to answer questions regarding skin disorders they may have experienced. Those reporting vitiligo (diagnosed or undiagnosed) or vitiligo signs (experiencing loss of skin colour but unaware of vitiligo and not diagnosed) were included in the analyses of vitiligo prevalence. Participants who self-reported physician-diagnosed vitiligo were given a broader survey to characterise disease progression, management and QoL (as measured with the Vitiligo-specific QoL [VitiQoL] instrument). RESULTS: The total estimated vitiligo prevalence among 35 694 survey participants (Europe, n = 18 785; USA, n = 8517; Japan, n = 8392) was 1.3% (diagnosed, 0.6%; undiagnosed, 0.4%; vitiligo signs, 0.3%). Among 219 patients formally diagnosed with vitiligo (Europe, n = 150; USA, n = 48; Japan, n = 21), total VitiQoL scores were associated with age (P = 0.00017), disease extent (P < 0.0001), disease progression (P < 0.0001), disease management (P < 0.0001) and time since diagnosis (P = 0.0015). Behaviour scores varied based on skin phototype (P = 0.024) and ethnicity (P = 0.048). Higher total VitiQoL scores were reported in patients with head lesions (P = 0.027) and those with head and hand and/or wrist lesions (P = 0.018). Substantial high concern (rated 8-10 on an 11-point Likert scale) for lesions was found across all body areas and varied with geographical region. CONCLUSIONS: The vitiligo prevalence rate may be higher than previously reported, with a substantial proportion attributed to people who have not received a formal diagnosis. Among formally diagnosed patients with vitiligo, QoL was most severely impacted by more progressive and higher extent of disease.

Modifiable factors related to life-space mobility in community-dwelling older adults: results from the Canadian Longitudinal Study on Aging.

BACKGROUND: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed. RESULTS: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed. CONCLUSION: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

International Initiative for Outcomes (INFO) for vitiligo: workshops with patients with vitiligo on repigmentation.

BACKGROUND: There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo. OBJECTIVES: To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo. METHODS: We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. RESULTS: Seventy-three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80-100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. CONCLUSIONS: This was the largest patients' outcomes workshop. We followed the guidance from the CSG-COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0-25%, 26-50%, 51-79%, 80-100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre-existing organisational support and the availability of funding.

Utilization of motor imagery in upper limb rehabilitation: a systematic scoping review.

OBJECTIVE: To determine how motor imagery is being delivered in upper limb rehabilitation to guide practice and research. DATA SOURCE: MEDLINE, PubMed, CINAHL, EMBASE, PsychINFO databases were searched from 1987 to November 2014 STUDY SELECTION: English, adults, any clinical population or diagnosis, intervention for upper limb with an outcome measure used. All types of studies were included. Two authors independently selected studies for review using consensus. DATA EXTRACTION: Seven motor imagery elements were extracted using a model implemented in sport research: PETTLEP model (Physical, Environment, Task, Timing, Learning, Emotion, and Perspective). RESULTS: The search yielded 1107 articles with 1059 excluded leaving 48 articles for full review. A total of 38 articles involved individuals with stroke, five articles involved individuals with complex regional pain syndrome, and five articles for other conditions. Motor imagery elements most commonly described were physical, environment, task, and perspective. Elements less commonly described were timing, learning, and emotional aspects. There were significant differences between study populations (e.g. stroke and complex regional pain syndrome) and within populations on how motor imagery was delivered. CONCLUSION: Many of the imagery elements reviewed are not being considered or reported on in the selected studies. How motor imagery is being delivered within and between populations is inconsistent, which may lead to difficulties in determining key elements of effectiveness.

Level of agreement of occupational titles between persons with traumatic brain injury and their informants.

BACKGROUND: Returning to work is one of the most important goals cited by individuals with traumatic brain injury (TBI). However, they may have difficulty evoking past work history. The ability to recall work history is integral to the rehabilitation process of return to work. OBJECTIVE: The aim of this study was to determine 1) the level of agreement on the reporting of occupations and 2) if agreement is affected when specific occupational details are required in recall between adults with traumatic brain injury and their informants. METHODS: This is a retrospective cohort study of 259 individuals, with moderate to severe traumatic brain injury, and their selected informants (e.g. spouse, parent). Interviews were conducted separately for the individual and respective informant to gather information on type of occupation at time of injury and at time of interview. Reported occupations were coded using a standard classification system. Level of agreement was analyzed by interclass correlation coefficients and percent agreement, and the significance of bias was calculated. RESULTS: Participants were a mean age of 44.5 at time of study with 40% employed compared to 77% at time of injury. Agreement between participants and their informants for occupational title was high for both time periods though more so at the time of injury compared to current status. Level of agreement for specificity was moderate to high however, decreased as need for specificity of detail increased. CONCLUSION: While participant-informant responses appear to be reliable for occupational classification, when detailed information is required corroborating information is likely needed.

COL1A1 C-propeptide cleavage site mutation causes high bone mass, bone fragility and jaw lesions: a new cause of gnathodiaphyseal dysplasia?

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant condition characterized by bone fragility, irregular bone mineral density (BMD) and fibro-osseous lesions in the skull and jaw. Mutations in Anoctamin-5 (ANO5) have been identified in some cases. We aimed to identify the causative mutation in a family with features of GDD but no mutation in ANO5, using whole exome capture and massive parallel sequencing (WES). WES of two affected individuals (a mother and son) and the mother's unaffected parents identified a mutation in the C-propeptide cleavage site of COL1A1. Similar mutations have been reported in individuals with osteogenesis imperfecta (OI) and paradoxically increased BMD. C-propeptide cleavage site mutations in COL1A1 may not only cause 'high bone mass OI', but also the clinical features of GDD, specifically irregular sclerotic BMD and fibro-osseous lesions in the skull and jaw. GDD patients negative for ANO5 mutations should be assessed for mutations in type I collagen C-propeptide cleavage sites.

Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency <0.005) compound heterozygous variants of unknown significance in SRTD genes (specificity >99%). Costs for consumables, laboratory processing and bioinformatic analysis were

Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis.

Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

Ranking Spain's medical schools by their performance in the national residency examination.

BACKGROUND: Medical school graduates in Spain must take a uniform national exam (called "examen MIR") in order to enter postgraduate training in a specialty. Its results offer a unique opportunity to rank medical schools according to this exam. OBJECTIVES: We measured differences in the MIR exam results among Spanish medical schools and assessed the stability of the MIR-based rankings for the period 2003-2011. RESULTS: In the year 2011 a total of 6873 residency positions nationwide were offered by the Spanish Ministry of Health, Social Services and Equality. These positions covered 47 specialties distributed over 231 training centers. A total of 11,550 medical graduates (including 1997 foreign graduates) took the MIR examination. Marked differences among medical schools were evident. The median graduate from medical school #1 and #29 occupied the positions 1477 and 5383, respectively. These figures correspond to a standardized ranking of 21 out of 100 for medical school #1 (that is, 1477/6873; half of medical school #1 obtained better [below position 21%] and half worse [over position 21%] results) and a standardized ranking of 70 out of 100 for medical school #29. While 81% of the medical school #1 graduates were amongst the best 3000 MIR exams and only 5% above the 5000 position the corresponding figures for medical school #29 graduates were 21% and 44%, respectively. The ranking position of the 29 medical schools was very stable between the years 2003 and 2011. CONCLUSION: There are marked differences in medical schools in Spain and these differences are very consistent over the years 2003-2011.

Review of enteric outbreaks in prisons: effective infection control interventions.

OBJECTIVES: To identify documented outbreaks, worldwide, of enteric illness in correctional facilities over the last 10 years to understand the epidemiology of the outbreaks and explicitly identify effective infection control measures. STUDY DESIGN: Review of literature and outbreak investigation reports. METHODS: Computer-aided searches of literature databases and systematic searches of government websites were completed to identify relevant outbreak reports. Reference lists were hand-searched to validate the electronic search methodology. Reports identified through personal communications with public health officials were also included. RESULTS: Of the 72 outbreaks meeting the inclusion criteria, 76% and 21% were associated with bacterial agents and viral agents, respectively. The majority of outbreaks were associated with Salmonella (n=20), Clostridium perfringens (n=14), norovirus (n=14), pathogenic Escherichia coli (n=10) and Campylobacter spp. (n=5). Transmission was primarily foodborne (67%). During an outbreak, the most common control measures included limiting movements of ill inmates and staff, and their exclusion from kitchen duty. The most common retrospectively reported preventative recommendations included monitoring food temperatures and effective infection control procedures. CONCLUSIONS: It is essential to monitor food temperatures to prevent enteric outbreaks in prisons. Training in safe food handling should be offered to inmates who work in the kitchen. Enteric outbreaks are best controlled by effective infection control practices, while active surveillance and early diagnosis may prevent further spread of illness.

Treatment of degloving injuries with autogenous full thickness mesh scrotal free grafts.

In this report, we evaluated the effectiveness of scrotal tissue as an autogenous free skin graft to treat cutaneous degloving injuries of the distal limb in dogs. Surgery was performed on two male intact dogs with distal extremity degloving wounds. Dog #1 had a tarsal degloving wound with exposure of the distal tibial and tarsal bones. Dog #2 had a degloving injury over the metacarpals. Wounds were treated with daily wet-to-dry bandages in order to develop a healthy bed of granulation tissue at the graft recipient site. Scrotal ablation castration was performed once the recipient site had been prepared. Subcutaneous and adipose tissue were excised from the scrotal graft and mesh slits were created. The graft was applied to the recipient site with monofilament absorbable simple interrupted sutures. Bandaging was performed postoperatively, and bandage changes occurred four, seven, nine and 11 days postoperatively. Follow-up was performed at 30 days. In dog #1, the tarsal degloving injury graft had first intention healing with 100% graft take on day 11. In dog #2, the metacarpal degloving injury graft had 90% graft take on day nine, with second intention healing adjacent to the fifth digit pad. The scrotum is often discarded at the time of scrotal ablation castration. Distal extremity wounds can be successfully treated with free skin grafts. In male dogs, the scrotum is a viable option as a full thickness mesh free graft for distal extremity reconstructive surgery.

Reactive oxygen species and redox-induced programmed cell death due to MK 886: cells ("soil") "trump" agent ("seed").

Micromolar concentrations of the five-lipoxygenase inhibitor, MK 886 induce a "type 1" (apoptotic, extrinsic, death domain, receptor-dependent, caspase-positive) form of programmed cell death in Bcl-2-positive U937 human monoblastoid and HL-60 myeloid leukemia cells. A "type 2" (intrinsic, mitochondria-dependent, autophagic, in some examples caspase-negative (Panc-1)) form is induced in Panc-1 pancreatic and PC3 prostate cell lines. The latter two lines from epithelial-derived solid human cancers are Bcl-2-negative. Micromolar MK 886 induces an acute rise in Ca2+ in washed, Ca2+-poor U937 and HL60 cells in Ca2+ and Mg2+-free Hank's buffer. In U937 cells, much of the increase, or more properly redistribution, is nuclear in location (HL-60 not tested). No MK-886-induced acute Ca2+ increase developed in Panc-1 or PC3 cells. Bcl-2-positive HeLa cervical cancer cells exhibited an acute MK 886-induced increase in Ca2+. In the U937, PC3 and Panc-1 cells examined, MK-886 rapidly increased oxidative stress and decreased mitochondrial membrane potential, indicating that neither event is directly determinative for the altered distribution of Ca2+ or the form of PCD observed. Inhibition of increased U937 Ca2+ by the anti-oxidant, N-acetyl-L-cysteine, the effects of inhibitors of mitochondrial function including antimycin A, atractyloside, cyclosporin A, the L/N channel blocker loperamide, the intracellular chelator BAPTA and 2 agents, HA-14 and 3-methyl-antimycin A3 that impair Bcl-2 function further define these events. These differences in the Ca2+ response and possibly also the form of PCD that results may depend upon the presence of Bcl-2 or a related protein participating in a juxta-nuclear / nuclear Ca2+ ion channel. The role of mitochondria, the mechanism by which increased oxidative stress initiates the rapid release of Ca2+ from intracellular, possibly juxta-nuclear / nuclear sites or its redistribution to U937 Ca2+ nuclei, and whether this "signal" or possibly even ROS themselves mandate the type of PCD observed, presumably by differential modulation of transcription, remain to be determined. Lastly, these results demonstrate that, as might be expected, "soil" (cell type) trumps "seed" (inciting agent)".

Disparate forms of MK 886-induced programmed death in BCL-2 (+) blood and BCL-2 (-) solid cancer cells and a putative "nuclear" Ca2+ channel: "soil" trumps "seed"?

UNLABELLED: The five-lipoxygenase inhibitor, MK 886, in micromolar concentration induces a "type 1" form of programmed cell death in U937 human monoblastoid cells and a "type 2" form in Panc-1 pancreatic and PC3 prostate cell lines. The latter two lines originate from epithelial-derived solid human cancers. An acute rise in Ca(2+) occurs in U937 and HL 60 myeloid cells, in U937 cells located in their nuclei (HL 60 not tested), both of which are Bcl-2 positive. The two solid cancer cell lines express neither of these features. Solid tumor-derived Bcl-2-positive HeLa cervical cancer cells exhibit an acute increase in Ca(2+) after challenge with MK 886. In U937, PC3 and Panc-1 cells tested, the agent acutely increases oxidative stress and decreases mitochondrial membrane potential, indicating that neither event is directly determinative for the form of PCD. The role of mitochondria and the mechanism by which increased oxidative stress initiates the acute rise in U937 "nuclear" Ca(2+), the contribution, if any, of Bcl-2 in initiating the Ca(2+) signal and the latter in mandating the type of PCD, presumably through differential modulation of transcription, remain to be determined. Lastly, these results demonstrate that "soil" trumps "seed". HYPOTHESIS: Despite similarities in response, including those of the mitochondria to micromolar concentrations of MK 886, hematopoietic and epithelial-derived non-hematopoietic solid cancer cell lines exhibit dissimilar forms of programmed cell death. These differences may depend upon the presence of Bcl-2 or a related protein participating in a juxta-nuclear/nuclear Ca(2+) ion-channel. Evidence for this supposition is discussed.

Acute changes in U937 nuclear Ca2+ preceding type 1 "apoptotic" programmed cell death due to MK 886.

BACKGROUND: MK 886, a 5-lipoxygenase inhibitor, induces a type 1 "apoptotic" form of programmed cell death in Bcl-2-positive U937 monoblastoid cells. In Ca2+-depleted, nonpermeabilized U937 cells studied with MK 886 in a Ca2+-free medium, an acute increase in Ca2+ occured within 10 to 20 seconds, detected with fura-2 measured with a spectrofluorimeter. METHODS AND RESULTS: The increased fluorescence was nuclear in location, as judged by confocal microscopy. The antioxidant, N-acetyl-L-cysteine, three agents that inhibit mitochondrialfunction at identified sites, antimycin A, atractyloside and cyclosporin A, the L/N-channel inhibitor, loperamide and BAPTA, an intracellular Ca+ chelator preloaded into cells each reduced the extent or prevented the acute MK 886-induced rise in Ca2+, as determined by radiometric detection. Rhodamine-2, a more selective mitochondrial Ca2+ probe, provided no evidence for nuclear Ca2+ originating from that extra-nuclear site or from the endoplasmic reticulum. With 2', 7'-dichloro-dihydrofluorescein-labelled cells to detect reactive oxygen species, MK 886 increased the initial fluorescent signal from a number of intracellular, largely extra-nuclear sites, including mitochondria. Two chemicals that inhibit the function of Bcl-2, HA14-1 and 2-methyl-antimycin A3, reduced the Ca2+ response to MK 886, if pre-incubated with the Bcl-2-positive U937 cells at 37 degrees C for several hours. MK 886 was previously shown to induce reactive oxygen species and a fall in mitochondrial membrane potential in both Bcl-2-positive U937 and in Bcl-2-negative PC-3 prostate and panc-1 pancreatic cancer cells. The latter solid tumor cells undergo an atypical "type 2" PCD without an acute rise in nuclear Ca2+. CONCLUSION: These results are consistent with an MK 886-induced increase of reactive oxygen species from intra-cellular sites including mitochondria which release Ca2+ located primarily at or near nuclei. These events may involve Bcl-2 participating in some form of Ca2+ channel and nuclear Ca2+ binding proteins undergoing conformational changes due to reactive oxygen species. Reasons for the different PCD responses in Bcl-2 positive lympho-hematopoietic compared to Bcl-2-negative solid cancer cell lines, respectively with and without the induced nuclear Ca2+ signal, remain to be defined.

An interaction between type 1 and type 2 programmed cell death and clonogenic survival.

UNLABELLED: We suggest two additional reasons why current, non-surgical therapies for most solid, epithelial-derived cancers can lack effectiveness. Studies with panc-1 human pancreatic cancer cells cultured with actinomycin D and/or MK 886 indicate firstly, that type 2 (intrinsic, autophagic, mitochondrial-dependent, MK 886-induced) programmed cell death is less effective than the type 1 (apoptotic, extrinsic, ligand-dependent, actinomycin D-induced) form in reducing the number of residual clonogenic cells, and secondly, that activation of cellular suicide during their combined culture results in a greater number of residual clonogenic cells compared with either agent alone. HYPOTHESIS: Based on results from the culture of panc-1 cells with MK 886 and/or actinomycin D, we suggest that in this system, and possibly in others: (a) type 2 programmed cell death is a less effective inhibitor of residual cells with clonogenic potential, and (b) activation together of both forms of PCD increases the number of residual clonogenic cells.

Fenceline contact of beef calves with their dams at weaning reduces the negative effects of separation on behavior and growth rate.

The purpose of this study was to examine the hypothesis that fenceline contact between beef calves and cows at weaning reduces indices of behavioral distress and associated temporary reductions in weight gain. One hundred Angus/Hereford-cross calves were randomly assigned to five treatments for 7 d in each of 3 yr to determine the effect of different weaning techniques on their behavior and subsequent growth. Treatments were 1) fenceline separation from dams on pasture (F-P), 2) total separation from dams on pasture (S-P), 3) total separation from dams in a drylot (corral) preconditioned to hay (S-D-P), 4) total separation from dams in a drylot not preconditioned to hay (S-D-NP), and 5) nonweaned controls on pasture (C-P). At the end of the 7-d postweaning period, all calves were placed on pasture in large groups. Calves were weighed weekly for 10 wk. In the days following weaning, F-P and C-P calves spent more time eating (grazing or eating hay) than S-P and S-D-NP calves (P < 0.05). The S-P calves spent more time walking (pacing) than calves in the other four treatments (P < 0.05), which did not differ. The S-P calves also spent less time lying down than C-P, F-P, and S-D-P calves (P < 0.05); S-P and S-D-NP calves did not differ in lying time. The F-P calves vocalized less than S-P and S-D-NP calves (P < 0.05). In general, treatment differences were greatest during the first 3 d following weaning with d 2 (20 to 30 h after weaning) showing the greatest disparity. The F-P calves spent approximately 60% of their time within 3 m of the fence separating them from their dams during the first 2 d following weaning, whereas F-P cows spent about 40% of their time within 3 m of the fence during this period. Postweaning cumulative body weight gains of the F-P calves were greater than the gains recorded for the calves in the three totally separated treatments (which did not differ). The F-P calves gained 95% more weight than the average calf in the three totally separated treatments in the first 2 wk and were still heavier at 10 wk (21.4 vs 11.0 kg, respectively, at 2 wk and 50.0 vs 38.2 kg, respectively, at 10 wk; P < 0.05). It was concluded that providing fenceline contact between beef calves and cows for 7 d following weaning reduces behavioral indices of distress seen in the totally separated calves. In addition, fenceline contact with dams at weaning minimizes losses in weight gain in the days following separation. Totally separated calves did not compensate for these early losses in weight gain even after 10 wk.

Addendum to a note regarding the success of biological and medical science.

Much like mathematics, the biological and medical sciences seem unreasonably successful, considering many potential obstacles to this outcome. A recent suggestion that data should be viewed as 'quantized', that each 'elementary system' contains a single 'bit' of information (A. Zeilinger, A foundational principle for quantum mechanics, Foundations of Physics 29 (1999) 631), would seem ultimately to underlie the coherent relationships between the perceived physical universe and mental constructs within and among mathematics, logic, the 'hard' sciences and those 'softer' sciences directly based on biochemical and physiologic mechanisms (A. Zeilinger, A foundational principle for quantum mechanics, Foundations of Physics 29 (1999) 631; H. C. Von Baeyer, In the beginning was the bit, New Scientist, 17 (2000) 26-30).