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Biomedical subjects

Michael J Solomon

Publications and source records attributed to Michael J Solomon.

At least 19 recordsLinked to original sources

Universal scaling for polymer chain scission in turbulence.

We report that previous polymer chain scission experiments in strong flows, long analyzed according to accepted laminar flow scission theories, were in fact affected by turbulence. We reconcile existing anomalies between theory and experiment with the hypothesis that the local stress at the Kolmogorov scale generates the molecular tension leading to polymer covalent bond breakage. The hypothesis yields a universal scaling for polymer scission in turbulent flows. This surprising reassessment of over 40 years of experimental data simplifies the theoretical picture of polymer dynamics leading to scission and allows control of scission in commercial polymers and genomic DNA.

Biophysical Phenomena↗

Structure and dynamics of colloidal depletion gels: coincidence of transitions and heterogeneity.

Transitions in structural heterogeneity of colloidal depletion gels formed through short-range attractive interactions are correlated with their dynamical arrest. The system is a density and refractive index matched suspension of 0.20 volume fraction poly(methyl methacyrlate) colloids with the nonadsorbing depletant polystyrene added at a size ratio of depletant to colloid of 0.043. As the strength of the short-range attractive interaction is increased, clusters become increasingly structurally heterogeneous, as characterized by number-density fluctuations, and dynamically immobilized, as characterized by the single-particle mean-squared displacement. The number of free colloids in the suspension also progressively declines. As an immobile cluster to gel transition is traversed, structural heterogeneity abruptly decreases. Simultaneously, the mean single-particle dynamics saturates at a localization length on the order of the short-range attractive potential range. Both immobile cluster and gel regimes show dynamical heterogeneity. Non-Gaussian distributions of single particle displacements reveal enhanced populations of dynamical trajectories localized on two different length scales. Similar dependencies of number density fluctuations, free particle number, and dynamical length scales on the order of the range of short-range attraction suggests a collective structural origin of dynamic heterogeneity in colloidal gels.

Journal Article↗

Stacking fault structure in shear-induced colloidal crystallization.

We report measurements of the spatial distribution of stacking faults in colloidal crystals formed by means of an oscillatory shear field at a particle volume fraction of 52% in a system where the pair potential interactions are mildly repulsive. Stacking faults are directly visualized via confocal laser scanning microscopy. Consistent with previous scattering studies, shear orders the initially amorphous colloids into close-packed planes parallel to the shearing surface. Upon increasing the strain amplitude, the close-packed direction of the (111) crystal plane shifts from an orientation parallel to the vorticity direction to parallel the flow direction. The quality of the layer ordering, as characterized by the mean stacking parameter, decreases with strain amplitude. In addition, we directly observe the three-dimensional structure of stacking faults in sheared crystals. We observe and quantify spatial heterogeneity in the stacking fault arrangement in both the flow-vorticity plane and the gradient direction, particularly at high strain amplitudes (gamma> or =3). At these conditions, layer ordering persists in the flow-vorticity plane only over scales of approximately 5-10 particle diameters. This heterogeneity is one component of the random layer ordering deduced from previous scattering studies. In addition, in the gradient direction, the stacking registry shows that crystals with intermediate global mean stacking probability are comprised of short sequences of face-centered cubic and hexagonal close-packed layers with a stacking that includes a component that is nonrandom and alternating in character.

Journal Article↗

Gelation and internal dynamics of colloidal rod aggregates.

The internal dynamics of fractal cluster gels of colloidal boehmite rods with aspect ratios r = 3.9, 8.6, and 30.1, and colloidal polystyrene spheres (r = 1) are reported. Increasing r decreases the minimum colloid volume fraction for gelation. The behavior of the dynamic structure factor of rod gels is consistent with the internal dynamics of a constrained Brownian fractal object. Colloidal boehmite gels display an abrupt transition from floppy to brittle dynamics at phi approximately 10(-4). Moreover, the fractal cluster size of rod gels is not the determinant of the relaxation time of density fluctuations as it is in spherical particle gels. Instead, the relative behavior of the magnitude and time scale of the constrained fluctuations suggests that the fractal rod network is viscously coupled only on local, rather than cluster, scales. We hypothesize that noncentral forces between the anisometric particles are responsible for this anomalous behavior.

Journal Article↗

Clinical trials in head and neck oncology: an evaluation of clinicians' willingness to participate.

BACKGROUND: This study investigated the individual and collective ("community") equipoise of surgeons and oncologists and their willingness to take part in each of six hypothetical randomized controlled trials in head and neck oncology. METHODS: A survey was mailed to Australasian head and neck specialists. RESULTS: Among 109 respondents (74% response), the scenario with the highest level of individual equipoise pertained to the use of adjuvant interferon for patients with high-risk malignant melanoma, with 45% indicating complete uncertainty between treatment approaches. Significant differences in levels of community equipoise were demonstrated between surgeons and oncologists for three of the scenarios. Willingness to participate in randomized controlled trials ranged from 39% to 72%. Increasing strength of treatment preference was associated with unwillingness to participate in randomized controlled trials for two of six scenarios. CONCLUSION: High levels of equipoise and willingness to participate in clinical research augur well for future randomized controlled trials in head and neck oncology.

Adult↗

Multiplex detection of surface molecules on colorectal cancers.

A technique of fluorescence multiplexing is described for analysis of the plasma membrane proteome of colorectal cancer cells from surgically resected specimens, enabling detection and immunophenotyping when the cancer cells are in the minority. A single-cell suspension was prepared from a colorectal tumour, and the mixed population of cells was captured on a CD antibody microarray. The cancer cells were detected using a fluorescently tagged antibody for carcinoembryonic antigen (CEA-Alexa647) or epithelial cell adhesion marker (EpCAM-Alexa488). Using this multiplexing procedure, dot patterns from colorectal cancers were distinct from those of adjacent normal tissue. Subtraction of the expression levels for each antigen from normal tissue from those for the cancer shows differential expression in the cancer of CD66c, CD15s, CD55, CD45, CD71, CD45RO, CD11b and CEA, in descending order. Cells captured on the same microarray were also labelled with fluorescent CD3-phycoerythrin antibody revealing the presence of tumour-infiltrating lymphocytes. The immunophenotypes of T lymphocytes from the tumour samples showed differential expression of HLA-DR, TCR alpha/beta, CD49d, CD52, CD49e, CD5, CD95, CD28, CD38 and CD71, in descending order. Fluorescence multiplexing of mixed cell populations captured on a single antibody microarray enables expression profiling of multiple sub-populations of cells within a tumour sample.

CD4 Antigens↗

Laparoscopic management of rectal endometriosis.

PURPOSE: Surgical treatment of females with rectal endometriosis is challenging. The aim of this study was to review the results of laparoscopic intervention in the management of females with this complex disorder. METHOD: All cases of complex tertiary referral pelvic endometriosis requiring laparoscopic surgical intervention of the rectum were identified and reviewed from a prospective database. RESULTS: Between April 1996 and August 2004, 95 patients with pelvic endometriosis involving the rectum had laparoscopic surgical procedures performed by one gynecologist and one colorectal surgeon. Eighty percent of rectal procedures were completed laparoscopically. Forty-three (45 percent) were treated with diathermy excision, 18 (19 percent) had shave partial-thickness disc excision, 20 (21 percent) had full-thickness disc excision (including 14 endoanally using a circular stapler), while 14 (15 percent) were managed with laparoscopic-assisted segmental low anterior resection. A history of rectal pain during defecation present only during menstruation (adjusted odds ratio=8.6, 95 percent confidence interval (CI)=1.8-41.2) and previous laparoscopy (adjusted odds ratio=3.2, 95 percent CI=1.2-8.3) independently predicted a need for more extensive surgery than diathermy excision. There were no rectal anastomotic leaks, with 8 percent overall morbidity. The only significant predictor of ongoing postoperative symptoms was a history of dyspareunia (P=0.03). CONCLUSIONS: Patients with complex endometriosis of the rectum can be safely managed laparoscopically using a multidisciplinary approach. This case series suggests that a history of rectal pain during defecation that occurs only during menstruation is predictive of females with more extensive rectal disease.

Adult↗

How does an historic control study of a surgical procedure compare with the "gold standard"?

PURPOSE: It has been suggested that nonrandomized studies of interventions can neither discriminate between the effect of an intervention and that of bias nor accurately estimate the magnitude of measured effects. This study was designed to compare the results of an historic control study of a surgical procedure with those of a subsequent randomized control trial conducted under similar circumstances. METHODS: The results of an historic control study and a randomized, controlled trial of the safety and efficacy of laparoscopic rectopexy for rectal prolapse that were conducted 17 months apart by the same group of surgeons at the same institution were compared in terms of direction and magnitude of measured effects. RESULTS: The historic control study was reliable in determining the direction of measured effects in six of six (100 percent) outcomes common between the two studies, and there was agreement on the statistical significance (or lack of it) in five (83 percent); however, the magnitude of measured effects for all but one outcome assessed was 33 to 107 percent larger than in the randomized, controlled trial. There was no agreement in the medical literature on the effect of the historic control design on the direction and magnitude of measured effects. CONCLUSIONS: The results of a surgical historic control trial compared favorably with those of a randomized, controlled trial conducted under similar circumstances in determining the direction of measured effects but tended to yield larger estimates of effect magnitudes. The medical literature is divided on the effect of the historic control study design on study outcomes and more research is required to further define its role in evidence-based surgery.

Colorectal Surgery↗

A systematic review of reasons for nonentry of eligible patients into surgical randomized controlled trials.

BACKGROUND: The low recruitment rates into surgical randomized controlled trials (RCTs) threaten the validity of their findings. We reviewed the reasons for nonentry of eligible patients into surgical RCTs that would form the basis for future prospective research. METHODS: A systematic review of the English language literature for studies reporting reasons for nonentry of eligible patients into surgical RCTs and of recommendations made to improve the low recruitment rates. RESULTS: We reviewed 401 articles, including 94 articles presenting the results of 62 studies: 23 reports of recruitment into real surgical RCTs, 11 surveys of patients regarding hypothetical surgical RCTs, 10 surveys of clinicians and 18 literature reviews. The most frequently reported patient-related reasons for nonentry into surgical RCTs were preference for one form of treatment, dislike of the idea of randomization, and the potential for increased demands. Distrust of clinicians caused by a struggle to understand, explicit refusal of a no-treatment (placebo) arm, and the mere inability to make a decision were frequently reported in studies of real RCTs and patient surveys, but were not emphasized in surveys of clinicians and review articles. Difficulties with informed consent, the complexity of study protocols, and the clinicians' loss of motivation attributable to lack of recognition were the most commonly reported clinician-related reasons. CONCLUSIONS: There seems to be a discrepancy between real reasons for nonentry of eligible patients into surgical RCTS and those perceived by the clinicians, which require further prospective research. A summary and discussion of main recommendations sighted in the literature is presented.

Health Status↗

The role of telomeres and telomerase in the pathology of human cancer and aging.

Cellular senescence, the state of permanent growth arrest, is the inevitable fate of replicating normal somatic cells. Postulated to underlie this finite replicative span is the physiology of telomeres, which constitute the ends of chromosomes. The repetitive sequences of these DNA-protein complexes progressively shorten with each mitosis. When the critical length is bridged, telomeres trigger DNA repair and cell cycle checkpoint mechanisms that result in chromosomal fusions, cell cycle arrest, senescence and/or apoptosis. Should senescence be bypassed at such time, continued cell divisions in the face of dysfunctional telomeres and activated DNA repair machinery can result in the genomic instability favourable for oncogenesis. The longevity and malignant progression of the thus transformed cell requires coincident telomerase expression or other means to negate the constitutional telomeric loss. Practically then, telomeres and telomerase may represent plausible prognostic and screening cancer markers. Furthermore, if the argument is extended, with assumptions that telomeric attrition is indeed the basis of cellular senescence and that accumulation of the latter equates to aging at the organismal level, then telomeres may well explain the increased incidence of cancer with human aging.

Aging↗

Publication bias in papers presented to the Australian Orthopaedic Association Annual Scientific Meeting.

BACKGROUND: The selective publication of articles based on factors, such as positive outcome, statistical significance and study size is known as publication bias. If publication bias is present, any clinical decision based on a review of the published work will also be biased. Publication bias has been shown in various specialties, based on review of publication rates for abstracts presented at major scientific meetings. This study was conducted to investigate publication bias in orthopaedics. METHODS: Abstracts presented at the 1998 Australian Orthopaedic Association Annual Scientific Meeting were reviewed independently by two reviewers. Details of sample size, study setting, country of origin, outcome and study type were recorded for each abstract. Publication within 5 years was ascertained by electronic searching of Medline and Embase databases and direct author contact. Logistic regression analysis was used to identify predictors of publication. RESULTS: The overall publication rate was 31%. Publication was more likely if the study was a laboratory study, rather than a clinical study (odds ratio (OR), 3.45; 95% confidence interval (CI) 1.69-7.01, P < 0.001). Sample size, country of origin, study type, statistical significance and positive outcome were not significantly associated with publication. CONCLUSION: According to this study, laboratory studies were significantly more likely to be published than clinical studies. In contrast to previous studies, publication bias due to the selective publication of papers with a positive outcome or those reporting statistical significance was not found.

Abstracting and Indexing↗

Non-entry of eligible patients into the Australasian Laparoscopic Colon Cancer Study.

BACKGROUND: There is currently a need to assess the reasons for non-entry of eligible patients into surgical randomized controlled trials to determine measures to improve the low recruitment rates in such trials. METHODS: Reasons for non-entry of all eligible patients not recruited into the Australasian Laparoscopic Colon Cancer Study were prospectively recorded using a survey completed by the participating surgeons for a period of 6 months. RESULTS: In the 6-month period of the study, 51 (45%) out of 113 eligible patients examined by the 18 actively participating surgeons were recruited into the trial. Eighty-nine reasons were recorded for the non-entry of the 62 eligible patients. The most commonly recorded reason was preference for one form of surgery (42%) or the surgeon (31%) by the patient (45 patients (73%) in total). This was followed by lack of time (10 patients (16%)), hospital accreditation (7 patients (11%)) or staffing/equipment (6 patients (10%)). Concern about the doctor-patient relationship or causing the patient anxiety was recorded for three (5%) and two (3%) patients, respectively. Recruitment was positively associated with the availability of a data manager (chi2 = 19.91; P < 0.001, odds ratio (95% confidence interval) = 9.50 (3.53-25.53)) and negatively associated with an increased caseload (more than five eligible patients seen by the surgeon in the study period) (continuity adjusted chi2 = 16.052; P < 0.001, odds ratio (95% confidence interval) = 0.11(0.04-0.30)). CONCLUSION: Having a preference for one form of surgery by the patient or the surgeon was the most common reason for non-entry of eligible patients in the Australasian Laparoscopic Colon Cancer Study. Concern about the doctor-patient relationship played a minimal role in determining the outcome of recruitment. Patient and surgeon preferences, caseload and the distribution of supportive staff such as data managers according to patient population density should be considered in the planning of future trials.

Aged↗

Direct visualization of colloidal rod assembly by confocal microscopy.

The development of model materials and image processing methods to directly visualize and quantify colloidal rod assembly by means of confocal laser scanning microscopy (CLSM) is reported. Monodisperse fluorescent colloidal rods are prepared by the uniaxial extensional deformation of sterically stabilized microspheres at elevated temperatures. The particles are stably dispersed in refractive index matching mixed organic solvents for CLSM. An image processing algorithm is developed to detect rod backbones and extract particle centroids and orientation angles from the CLSM image volumes. By means of these methods we quantify the distribution of rod orientation angles in self-assembled structures of rods formed by sedimentation. We find the observations to be consistent with aspect-ratio-dependent jamming and orientational order/disorder transition in the rod sediments.

Journal Article↗

Long-term indwelling seton for complex anal fistulas in Crohn's disease.

PURPOSE: This study was designed to review the results of long-term indwelling seton or depezzar catheter in the management of perianal Crohn's disease. METHODS: A retrospective case review from data extracted from a prospective endorectal ultrasound database was performed. All patients underwent an intraoperative endorectal ultrasound to identify the extent of the fistulas and to assess anal wall thickness. Fistulas were classified by Parks' criteria. All patients then underwent insertion of a seton or depezzar catheter under ultrasound guidance. All patients were followed clinically and with endorectal ultrasound by the senior author. Outcome measures included symptom control, number of procedures required, fecal continence, and reduction in anal wall thickness. RESULTS: Twenty-eight patients with 43 complex perianal Crohn's fistulas were identified. Median follow-up was 13 (range, 2-81) months. Twenty-one percent of patients developed recurrent or new perianal symptoms while the seton was in situ. Eleven percent of patients required further surgical intervention. The median anal wall thickness at the time of diagnosis was 18.5 mm reducing to a median of 14 mm after seton insertion and symptom control (P < 0.02). No patient reported a deterioration in fecal continence after seton insertion. In multivariate analysis, patient age (P < 0.005), reduction in anal wall thickness after seton insertion (P < 0.04), and length of follow-up (P < 0.03) were significant predictors of long-term symptom control. CONCLUSIONS: Long-term indwelling seton is an effective management modality for complex perianal Crohn's fistulas, which does not negatively impact fecal continence. Clinical symptoms and course are associated with anal wall thickness as measured by endorectal ultrasound.

Adolescent↗

Telephone vs. face-to-face biofeedback for fecal incontinence: comparison of two techniques in 239 patients.

PURPOSE: Biofeedback is an effective treatment for patients with fecal incontinence, yet little is known about how it works or the minimum regime necessary to provide clinical benefit. This study compares the effectiveness of a novel protocol of telephone-assisted biofeedback treatment for patients living in rural and remote areas with the standard face-to-face protocol for patients with fecal incontinence. METHODS: A new treatment program comprising an initial face-to-face assessment and treatment with transanal manometry and ultrasound biofeedback, followed by three treatments conducted via telephone and a final face-to-face assessment, was developed. Standard treatment involved five face-to-face treatment sessions with manometry and ultrasound. Patients from rural areas were offered the telephone-assisted treatment protocol. Data gathered prospectively included incontinence scores, a quality of life index, anal manometry, and external sphincter isometric and isotonic fatigue times. RESULTS: A total of 239 consecutive patients treated between July 2001 and July 2004 were enrolled. There were no significant differences in demographic details, past history, or pretreatment measures of the two groups. Forty-six of 55 patients (84 percent) treated with the telephone protocol and 129 of 184 (70 percent) treated by the standard technique completed treatment. There were substantial, significant improvements after treatment, including 54 percent mean improvement in patient's own rating of their incontinence in both groups; a mean decrease of 3.1 and 3.2 on the St. Mark's incontinence score (from 7.9 to 4.7 and 7.4 to 4.2 of 13) and relative improvements of 128 and 130 percent in the quality of life index (from 0.29 to 0.65 and 0.3 to 0.69 of 1) for the telephone-assisted and standard groups respectively. Importantly, there were no significant differences between the telephone-assisted or standard groups in any outcome. Of patients who completed treatment, 78 percent were better or much better. CONCLUSIONS: A less intensive regime of biofeedback seems to be equally effective as the standard intensive protocol. This finding adds weight to the evolving concept that the physical aspects of biofeedback treatment, such as manometry or ultrasound, may not be necessary in the treatment of most patients with fecal incontinence. This needs to be further tested in a randomized, controlled trial.

Adult↗

Is it worth the risk? A systematic review of instruments that measure risk propensity for use in the health setting.

In this era of shared doctor-patient decision-making, eliciting and incorporating patients' treatment choices is essential to ensure all patients receive the treatment that is right for them. Clinicians and researchers should fully understand the many factors that influence and guide patients in their preferences for treatment. One of these influences is an individual's general risk propensity or willingness to take risks, yet there is little in the literature about methods for measuring risk propensity. A systematic review was undertaken to identify instruments that measure risk propensity and to appraise their validity and relevance for a clinical setting. Of 3546 articles, 139 were potentially relevant. From these, 14 instruments were identified. Eight measured risk propensity, whereas six measured personality traits associated with risk propensity. Most instruments demonstrated good internal reliability but their appropriateness for patients, particularly older adults, remains unclear. While no instrument was specific to or tested in a clinical setting, instruments that directly measured risk propensity were considered to be the most useful for clinical populations. The further adaptation and validation of these instruments among older adults are important avenues for future research.

Choice Behavior↗