Venture Capital in US Medicine: A Briefing for Radiologists.

In recent years, there has a been a rapid and significant drop in the number of private practices in US radiology. Many factors have driven this change. One of the most important has been the corporatization of practices. In many cases, this involves third-party financing, one type of which is venture capital. This article will provide an introduction to the venture capital investment model for medical professionals.

Mass spectrometric-based assessment of the serum kappa to lambda immunoglobulin light chain ratio (κ:λ) in dogs with immunoglobulin secretory diseases.

The ratio of κ light chains to λ light chains (κ:λ) in serum is used as a biomarker of immunoglobulin secreting neoplasia in humans but has not been evaluated in dogs. A mass-spectrometry based method for determining the canine serum κ:λ was developed and used to evaluate samples from control dogs, dogs with an infectious aetiology, dogs with secretory plasma cell tumours (sPCT) and dogs with non-secretory B cell neoplasia. A human-targeted immunoturbidometric κ:λ assay and immunofixation using antisera targeting human κ light chain or λ light chain was also performed on all samples. Using whole serum samples, the MS-based κ:λ method identified 5 sPCT as κ-predominant (mean κ:λ = 3.307) and 5 sPCT as λ-predominant (mean κ:λ = 0.023) and documented differences between these groups and all other groups (p < 0.05 for all). The infectious aetiology group had a lower mean κ:λ ratio (mean κ:λ = 0.069) than control samples (mean κ:λ = 0.103, p = 0.035). Similar results were obtained when samples were enriched for proteins between 10 and 50 kDa using size exclusion chromatography, except for the statistical difference between the control and infectious aetiology group. All λ-predominant cases had only anti-human λ light chain labelling by immunofixation. Three κ-predominant cases had only anti-human κ-light chain labelling and the remaining two cases did not label with either antisera by immunofixation. The immunoturbidometric method had high analytical CV% (λ light chain CV = 13%, κ light chain CV = 50%), was unable to measure light chains in 20.5% of samples and did not distinguish groups. The data suggests that the human-targeted immunoturbidometric method would not be diagnostically useful and that the MS-derived serum κ:λ may be a useful biomarker of canine immunoglobulin secretory neoplasia which may have the ability to distinguish neoplasia from infectious causes of immunoglobulin secretion.

A retrospective study to assess resource utilization and costs in patients with post-stroke spasticity in the United Kingdom.

OBJECTIVE: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. METHODS: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. RESULTS: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. CONCLUSION: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Do female Nicrophorus vespilloides reduce direct costs by choosing males that mate less frequently?

Sexual conflict occurs when selection to maximize fitness in one sex does so at the expense of the other sex. In the burying beetle Nicrophorus vespilloides, repeated mating provides assurance of paternity at a direct cost to female reproductive productivity. To reduce this cost, females could choose males with low repeated mating rates or smaller, servile males. We tested this by offering females a dichotomous choice between males from lines selected for high or low mating rate. Each female was then allocated her preferred or non-preferred male to breed. Females showed no preference for males based on whether they came from lines selected for high or low mating rates. Pairs containing males from high mating rate lines copulated more often than those with low line males but there was a negative relationship between female size and number of times she mated with a non-preferred male. When females bred with their preferred male the number of offspring reared increased with female size but there was no such increase when breeding with non-preferred males. Females thus benefited from being choosy, but this was not directly attributable to avoidance of costly male repeated mating.

Clinical diagnosis of symptomatic midfoot osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

OBJECTIVE: To derive a multivariable diagnostic model for symptomatic midfoot osteoarthritis (OA). METHODS: Information on potential risk factors and clinical manifestations of symptomatic midfoot OA was collected using a health survey and standardised clinical examination of a population-based sample of 274 adults aged ≥50 years with midfoot pain. Following univariable analysis, random intercept multi-level logistic regression modelling that accounted for clustered data was used to identify the presence of midfoot OA independently scored on plain radiographs (dorso-plantar and lateral views), and defined as a score of ≥2 for osteophytes or joint space narrowing in at least one of four joints (first and second cuneometatarsal, navicular-first cuneiform and talonavicular joints). Model performance was summarised using the calibration slope and area under the curve (AUC). Internal validation and sensitivity analyses explored model over-fitting and certain assumptions. RESULTS: Compared to persons with midfoot pain only, symptomatic midfoot OA was associated with measures of static foot posture and range-of-motion at subtalar and ankle joints. Arch Index was the only retained clinical variable in a model containing age, gender and body mass index. The final model was poorly calibrated (calibration slope, 0.64, 95% CI: 0.39, 0.89) and discrimination was fair-to-poor (AUC, 0.64, 95% CI: 0.58, 0.70). Final model sensitivity and specificity were 29.9% (95% CI: 22.7, 38.0) and 87.5% (95% CI: 82.9, 91.3), respectively. Bootstrapping revealed the model to be over-optimistic and performance was not improved using continuous predictors. CONCLUSIONS: Brief clinical assessments provided only marginal information for identifying the presence of radiographic midfoot OA among community-dwelling persons with midfoot pain.

Evaluation of an HIV prevention intervention designed for African American Women: results from the SISTA Community-Based Organization Behavioral Outcomes Project.

One of the Centers for Disease Control and Prevention's strategies for addressing racial disparities within the HIV epidemic is to support the implementation of HIV prevention behavioral interventions designed for African Americans. One such intervention is Sisters Informing Sisters about Topics on AIDS (SISTA), a culturally relevant and gender-specific, five-session, group-level, HIV prevention intervention designed for African American women. In 2008, the Centers for Disease Control and Prevention funded five community-based organizations to conduct outcome monitoring of SISTA to assess the outcomes associated with implementation in the field. Using a 90-day recall, demographic and sexual risk data were collected from participants at baseline and at 90 and 180 days post-intervention. Findings reveal that women participating in SISTA (n = 432) demonstrated a significant reduction in sexual risk between baseline and both follow-up time points for each of the six outcomes being measured (e.g., any unprotected sex, all protected sex).

Iatrogenic nerve injury in a national no-fault compensation scheme: an observational cohort study.

BACKGROUND: Iatrogenic nerve injury causes distress and disability, and often leads to litigation. The scale and profile of these injuries has only be estimated from published case reports/series and analyses of medicolegal claims. AIM: To determine the current spectrum of iatrogenic nerve injury in New Zealand by analysing treatment injury claims accepted by a national no-fault compensation scheme. METHODS: The Accident Compensation Corporation (ACC) provides national no-fault personal accident insurance cover, which extends to patients who have sustained a treatment injury from a registered healthcare professional. Nerve injury claims identified from 5227 treatment injury claims accepted by the ACC in 2009 were analysed. RESULTS: From 327 claims, 292 (89.3%) documenting 313 iatrogenic nerve injuries contained sufficient information for analysis. Of these, 211 (67.4%) occurred in 11 surgical specialties, particularly orthopaedics and general surgery; the remainder involved phlebotomy services, anaesthesia and various medical specialties. The commonest causes of injury were malpositioning (n = 40), venepuncture (n = 26), intravenous cannulation (n = 21) and hip arthroplasty (n = 21). Most commonly injured were the median nerve and nerve roots (n = 32 each), brachial plexus (n = 26), and the ulnar nerve (n = 25). At least 34 (11.6%) patients were referred for surgical management of their nerve injury. CONCLUSIONS: Iatrogenic nerve injuries are not rare and occur in almost all branches of medicine, with malpositioning under general anaesthesia and venepuncture as leading causes. Some of these injuries are probably unavoidable, but greater awareness of which nerves are at risk and in what context should facilitate the development and/or wider implementation of preventive strategies.

A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans.

Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD). To validate the method, we compared in vivo contractile properties of the quadriceps muscle with the fiber-type composition and oxidative enzyme capacity. We used a Magstim Rapid(2) magnetic nerve stimulator with the coil wrapped around the quadriceps. Stimuli were given at 30 Hz, a duty cycle of 0.4 (2 s on, 3 s off), and for 50 trains. Force generation and the surface electromyogram were measured throughout. Quadriceps twitch force, elicited by supramaximal magnetic stimulation of the femoral nerve, was measured before and after the protocol. Quadriceps muscle biopsies were analyzed for oxidative (citrate synthase, CS) and glycolytic (phosphofructokinase, PFK) enzyme activity and myosin heavy chain isoform protein expression. The time for force to fall to 70% of baseline (T(70)) was shorter in the COPD group than the control group: 55.6 +/- 26.0 vs. 121 +/- 38.7 s (P = 0.0014). Considering patients and controls together, positive correlations were observed between T(70) and the proportion of type I fibers (r = 0.68, P = 0.004) and CS-to-PFK ratio (CS/PFK) (r = 0.67, P = 0.005). We conclude that quadriceps endurance assessed using rMS is feasible in clinical studies.

Assessment of tube current modulation in pelvic CT.

An anatomically shaped polymethylmethacrylate (PMMA) phantom was used to assess the effect of the Siemens CARE Dose mA modulation system on pelvic CT scans. The effect of the system on absorbed dose to air, image percentage noise and the signal to noise ratio of clinically relevant details was assessed. The signal to noise ratio was calculated using Polytetrafluoroethylene (PTFE) and distilled water inserts; PTFE was used to represent bony structure and distilled water was used to represent soft tissue abscess. Pelvis protocols identified from local hospitals and the UK CT Dose Survey (2002), were assessed and compared with those provided by Siemens Medical (UK). These protocols were tested on a Siemens Sensation 4 CT scanner, both with and without CARE Dose. Results were obtained which showed that dose savings were possible with no significant increase in image noise. Dose reductions were 8% in the lateral positions in the phantom and 42% in the centre, top and bottom. The calculated "CTDIvol" was 32% lower with CARE Dose than without CARE Dose. This is slightly greater than the 25% change in the effective mAs values that was found. This implies that the reduction in the effective mAs values is a reasonable predictor of the total reduction in absorbed dose to air, whilst slightly underestimating the actual change. The results also showed a non-significant trend towards decreased signal to noise ratios for clinically relevant CT numbers when CARE Dose was activated. This suggests that tube current modulation may detrimentally affect signal detection due to changes in image noise.

Egg size-number trade-off and a decline in oviposition site choice quality: female Pararge aegeria butterflies pay a cost of having males present at oviposition.

Once mated, the optimal strategy for females of the monandrous butterfly, Pararge aegeria, is to avoid male contact and devote as much time as possible to ovipositing, as there is little advantage for females to engage in multiple matings. In other butterfly species the presence of males during egg laying has been shown to affect aspects of oviposition behavior and it has been suggested that repeated interference from males has the potential to reduce reproductive output. The aim of this study was to assess the effects of male presence during oviposition on reproductive output and behavior of a population of P. aegeria obtained from Madeira Island, Portugal, and maintained in the laboratory. Two experiments were performed where females were housed individually in small cages. Experiment 1 examined how social factors influenced the egg laying behavior of females. To do this the presence or absence of males was manipulated and egg size and number was measured over the first 14 days of oviposition. It was observed that when males were present during oviposition females made a trade-off between egg size and number. Experiment 2 examined how social factors affected oviposition site choice. Again, male presence/absence was manipulated, but in this experiment where the female laid her egg in relation to host quality was scored, and the size of the egg laid was measured. In the absence of males females selectively positioned their larger eggs on good quality host plants. However, selective oviposition was no longer observed when females were in the presence of males. We suggest that P. aegeria females from the Madeira Island population are adapted for a flexible oviposition strategy, governed by external cues, allowing a trade-off between egg size and number when the time available for egg laying is limiting.

Blue cone monochromatism: a phenotype and genotype assessment with evidence of progressive loss of cone function in older individuals.

AIM: To perform a detailed clinical and psychophysical assessment of the members of three British families affected with blue cone monochromatism (BCM), and to determine the molecular basis of disease in these families. METHODS: Affected and unaffected members of three families with BCM were examined clinically and underwent electrophysiological and detailed psychophysical testing. Blood samples were taken for DNA extraction. The strategy for molecular analysis was to amplify the coding regions of the long wavelength-sensitive (L) and middle wavelength-sensitive (M) cone opsin genes and the upstream locus control region by polymerase chain reaction, and to examine these fragments for mutations by direct sequencing. RESULTS: We have confirmed the reported finding of protan-like D-15 arrangements of patients with BCM. In addition, we have demonstrated that the Mollon-Reffin (MR) Minimal test is a useful colour-discrimination test to aid in the diagnosis of BCM. Affected males were shown to fail the protan and deutan axes, but retained good discrimination on the tritan axis of the MR test, a compelling evidence for residual colour vision in BCM. This residual tritan discrimination was also readily detected with HRR plates. In two families, psychophysical testing demonstrated evidence for progression of disease. In two pedigrees, BCM could be linked to unequal crossovers within the opsin gene array that resulted in a single 5'-L/M-3' hybrid gene, with an inactivating Cys203Arg mutation. The causative mutations were not identified in the third family. CONCLUSIONS: The MR test is a useful method of detecting BCM across a wide range of age groups; residual tritan colour discrimination is clearly demonstrated and allows BCM to be distinguished from rod monochromatism. BCM is usually classified as a stationary cone dysfunction syndrome; however, two of our families show evidence of progression. This is the first report of progression associated with a genotype consisting of a single 5'-L/M-3' hybrid gene carrying an inactivating mutation. We have confirmed that the Cys203Arg inactivating mutation is a common sequence change in blue cone monochromats.

A comparison of three modelling approaches for quantitative risk assessment using the case study of Salmonella spp. in poultry meat.

A comprehensive review of both the scientific literature and industry practices was undertaken to identify and quantify all sources of contamination throughout the entire poultry meat production chain by Salmonella spp. This information was used to develop a quantitative risk assessment (QRA) model for Salmonella in the production chain from the breeder farm to the chilled carcass. This was subsequently used as the basis on which to compare the merits of three approaches to QRA modelling in such systems. The original model used a Bayesian Network (BN). The second method was a Markov chain Monte Carlo (MCMC) approach, a numerical Bayesian technique which retained a similar network structure but allowed further development, such as the separation of variability and uncertainty. The third method was a more detailed simulation model. The BN responds immediately to changes, such as entering evidence, because it does not use simulation and can propagate information from any point in the network to all others by Bayesian inference. However, it requires all the variables to be discrete, which introduces errors if continuous variables have to be discretized. These errors can accumulate. The MCMC approach does not require discrete variables while retaining some of the properties of the BN model, such as the ability to draw inferences from evidence. Finally, the simulation offers greater flexibility, such as consideration of the individual carcass, but may be more complex to implement as a result and sacrifices the ability to propagate evidence.

Meeting the needs of patients with COPD: patients' preference for the Diskus inhaler compared with the Handihaler.

This study assessed preference and ease of use of the Diskus and the Handihaler in symptomatic chronic obstructive pulmonary disease (COPD) patients. No patient had used either device before. Patients were given a questionnaire to assess the inhalers and to rank the most important feature of an inhaler. Patients in Germany (n = 125) and The Netherlands (n = 131) with a mean age of 60 participated. Fifty-eight percent of German patients and 69% of Dutch patients had no problems using the Diskus compared to only 11 and 32%, respectively, using the Handihaler (p < 0.001). Overall, 79% of patients would be happy to use the Diskus and 46% the Handihaler if their physician suggested it. However, 35% of Dutch patients and 72% of German patients stated they would not be happy to use the Handihaler. The Diskus was rated higher than the Handihaler for the top three features of an ideal inhaler. Overall the Diskus inhaler was preferred by 67% of patients.

An assessment of the microbiological risks involved with egg washing under commercial conditions.

The potential benefits of washing eggs is offset by a historical perception in the European Union that wetted eggs are prone to spoilage and water loss. This study describes the effects of spray jet washing under various processing conditions to shell surface counts of Salmonella and the presence of bacteria in egg contents. Experiments used eggs that were contaminated with Salmonella Enteritidis PT4 or Salmonella Typhimurium DT104 before cuticle hardening. Washing of contaminated eggs under optimum conditions resulted in a more than 5-log reduction of Salmonella counts from the shell surface. Salmonella was not isolated from the yolk or albumen of any egg washed by the optimal protocol, suggesting that when properly controlled, egg washing did not cause Salmonella to enter the contents. However, contamination did arise if strict control was not maintained over the wash and rinse water temperatures. Both Salmonella Enteritidis and Salmonella Typhimurium were shown to enter the egg contents when water temperatures were lowered, indicating that strict temperature control must be maintained in order to prevent the ingress of Salmonella into egg contents. Other washing machine parameters that were investigated did not significantly affect Salmonella entry into the egg contents but influenced shell surface kill levels to varying degrees.

Problems with HIV/AIDS prevention, care and treatment in Togo, West Africa: professional caregivers' perspectives.

This paper used accounts of professional caregivers to HIV/AIDS patients in Lomé, Togo, West Africa to explore the impacts of cultural, institutional and socio-economic factors in the fight against HIV/AIDS. Thirteen health professionals and 17 non-health professionals who work with people living with HIV/AIDS were interviewed in June and July 2002 in Lomé, Togo. The study found that, in Togo there are some cultural, socio-economic and institutional practices that put Togolese at risk of contracting HIV and complicate the care of those who become infected. People with HIV/AIDS face socio-economic, emotional and psychological battles as they attempt to deal with their physical health and the social reactions to such a stigmatizing disease. Thus, in order to contain the spread of HIV/AIDS, people living with HIV/AIDS, family caregivers, traditional healers as well as the public must be educated about the importance of preventing the disease and how each group can help achieve success in its control. Interventions in prevention and care should be designed with an awareness of these structural factors that contribute to the spread of AIDS and compromise the quality of care given to those who become infected.

A comparison of magnetic resonance imaging and neurophysiological studies in the assessment of cervical radiculopathy.

Neurophysiological studies (NPS) are often used by both neurosurgeons and neurologists to supplement neuroimaging findings in the diagnosis of cervical radiculopathy and in operative decision-making. The aim of this study was to assess whether nerve conduction and electromyographic studies added significant information to that obtained from high resolution MRI to warrant routine use. Over the 10-year period (1991-2001), we identified 48 patients who underwent both preoperative NPS and MRI for cervical radiculopathy. Sensitivity of MRI and NPS for diagnosing cervical radiculopathy was 93 and 42%, respectively. Whilst the positive predictive values for MRI and NPS were similar (91% versus 86%), the former had a higher negative predictive value (25% versus 7%). In only one case was the decision to operate based on NPS despite a negative MRI. We therefore suggest that in patients with clinical and MRI evidence of cervical radiculopathy, NPS has limited additional diagnostic value.