Rosette-induced separation of T cells by acoustophoresis.

Breakthrough cell therapies for the treatment of cancers require the separation of specific cells, such as T cells, from the patient's blood. Current cell therapy processes rely on magnetic separation, which adds clinical risk and requires elevated manufacturing controls due to the added foreign material that constitutes the magnetic beads. Acoustophoresis, a method that uses ultrasound for cell separation, has demonstrated label-free enrichment of T cells from blood, but residual other lymphocytes limit the ultimate purity of the output T cell product. Here, to increase the specificity of acoustophoresis, we use affinity reagents to conjugate red blood cells with undesired white blood cells, resulting in a cell-cell complex (rosette) of increased acoustic mobility. We achieve up to 99% purity of T cells from blood products, comparable to current standards of magnetic separation, yet without the addition of separation particles.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe.

BACKGROUND: Universal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. METHODS: For this observational retrospective cohort study, time series data (2001-2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. RESULTS: The population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4-7 weeks. CONCLUSIONS: The introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Impact of weight management nutrition interventions on dietary outcomes in children and adolescents with overweight or obesity: a systematic review with meta-analysis.

BACKGROUND: The impact of obesity interventions on dietary intake in children and adolescents with overweight or obesity is unclear. This systematic review aimed to investigate the impact of the dietary component of weight management interventions on the change in diet in children and adolescents with overweight or obesity. METHODS: Eligible randomised controlled trials (RCTs) published between 1975 and 2020 were identified by a systematic search following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Meta-analyses of eligible study outcomes were performed using statistical software. A multilevel random effects model was used with three significant random effects fitted using restricted maximum likelihood estimation. RESULTS: This review identified 109 RCTs, including 95 that reported at least one statistically significant dietary outcome change and 14 reporting no significant dietary change. Results from the meta-analyses (n = 29 studies) indicated that, compared to control groups, intervention groups achieved significantly greater reductions in mean total energy intake at ≤6 months (-194 kcal day-1 , 95% confidence interval = -275.80 to -112.90 kcal day-1 , P < 0.001) and up to 12 months (-112 kcal day-1 95% confidence interval = -218.92 to -5.83 kcal day-1 ) P = 0.038), increases in fruit and/or vegetable intakes over 2-12 months (n = 34, range +0.6 to +1.5 servings day-1 ) and reductions in consumption of sugar-sweetened beverages (n = 28, range -0.25 to -1.5 servings day-1 ) at 4-24 months follow-up. CONCLUSIONS: Obesity interventions with a dietary component have a modest but sustained impact on reducing total energy intake and improving intakes of specific food groups in children and adolescents with overweight or obesity. High quality RCTs that are powered to detect change in diet as a primary outcome are warranted.

Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype.

Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here we show that on injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In profibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface-associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype.

Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the U.K. Clinical Practice Research Datalink.

BACKGROUND: Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified. OBJECTIVES: To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England. METHODS: This population-based cohort study used anonymized U.K. primary care data linked to hospitalization and deprivation data. Individuals aged ≥ 65 years without prior zoster history (N = 862 470) were followed from 1 September 2003 to 31 August 2013. Poisson regression was used to obtain adjusted rate ratios (ARRs) for the association of sociodemographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by comorbidities and immunosuppressive medications was also assessed. RESULTS: There were 37 014 first zoster episodes, with an incidence of 8·79 [95% confidence interval (CI) 8·70-8·88] per 1000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher vs. those not in care homes), being a woman (16% higher vs. men), nonimmigrants (~30% higher than immigrants) and white ethnicity (for example, twice the rate compared with those of black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most vs. least deprived 0·96 (95% CI 0·92-0·99) and among those living alone (ARR 0·96, 95% CI 0·94-0·98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1·11 to 3·84). CONCLUSIONS: The burden of zoster was higher in specific sociodemographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

Endometrial carcinoma recurrence according to race and ethnicity: An NRG Oncology/Gynecologic Oncology Group 210 Study.

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype-stratified models, higher EC recurrence was noted in NHB women with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11-2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.

Trends in the burden of varicella in UK general practice.

Childhood varicella vaccination has not yet been introduced in the UK. To inform decision-making about future vaccine programmes, data on the burden of varicella in general practice over a 10-year period (01/01/2005-31/12/2014) was calculated by age and ethnicity, using anonymised data from >8 million individuals in the Clinical Practice Research Datalink. Varicella consultations peaked at 20 603 in 2007, then decreased annually in all age groups to 11 243 in 2014. Each year, consultation rates were common among infants, were highest among 1-3 year olds (61·2 consultations/1000 person-years in 2007, 39·7/1000 person-years in 2014) and then fell with increasing age to <1·0/1000 person-years at ages ⩾20 years. Varicella acquisition appeared to be delayed in some ethnic groups, with lower consultation rates for children aged <3 years but increased rates for older children and adults aged ⩽40 years among those of black African, Afro-Caribbean, South Asian or other Asian ethnicity. Decreasing general practice consultation rates over time could reflect changes in healthcare utilisation, with patients seeking care in alternative settings such as Accident and Emergency Departments, although current data prevent full assessment of this. Availability of data on varicella diagnoses across all health settings would enable estimation of the total healthcare burden due to varicella and the cost-effectiveness of introducing varicella vaccination.

Pharmacogenetics of pemetrexed combination therapy in lung cancer: pathway analysis reveals novel toxicity associations.

Identification of polymorphisms that influence pemetrexed tolerability could lead to individualised treatment regimens and improve quality of life. Twenty-eight polymorphisms within eleven candidate genes were genotyped using the Illumina Human Exome v1.1 BeadChip and tested for their association with the clinical outcomes of non-small cell lung cancer and mesothelioma patients receiving pemetrexed/platinum doublet chemotherapy (n=136). GGH rs11545078 was associated with a reduced incidence of grade ⩾3 toxicity within the first four cycles of therapy (odds ratio (OR) 0.25, P=0.018), as well as reduced grade ⩾3 haematological toxicity (OR 0.13, P=0.048). DHFR rs1650697 conferred an increased risk of grade ⩾3 toxicity (OR 2.14, P=0.034). Furthermore, FOLR3 rs61734430 was associated with an increased likelihood of disease progression at mid-treatment radiological evaluation (OR 4.05, P=0.023). Polymorphisms within SLC19A1 (rs3788189, rs1051298 and rs914232) were associated with overall survival. This study confirms previous pharmacogenetic associations and identifies novel markers of pemetrexed toxicity.

Regional-specific alterations in cell-cell junctions, cytoskeletal networks and myosin-mediated mechanical cues coordinate collectivity of movement of epithelial cells in response to injury.

This study investigates how epithelial cells moving together function to coordinate their collective movement to repair a wound. Using a lens ex vivo mock cataract surgery model we show that region-specific reorganization of cell-cell junctions, cytoskeletal networks and myosin function along apical and basal domains of an epithelium mediates the process of collective migration. An apical junctional complex composed of N-cadherin/ZO-1/myosin II linked to a cortical actin cytoskeleton network maintains integrity of the tissue during the healing process. These cells' basal domains often preceded their apical domains in the direction of movement, where an atypical N-cadherin/ZO-1 junction, linked to an actin stress fiber network rich in phosphomyosin, was prominent in cryptic lamellipodia. These junctions joined the protruding forward-moving lamellipodia to the back end of the cell moving directly in front of it. These were the only junctions detected in cryptic lamellipodia of lens epithelia migrating in response to wounding that could transmit the protrusive forces that drive collective movement. Both integrity of the epithelium and ability to effectively heal the wound was found to depend on myosin mechanical cues.

A central role for vimentin in regulating repair function during healing of the lens epithelium.

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.

Intraperitoneal chemotherapy requires expertise and should be the standard of care for optimally surgically resected epithelial ovarian cancer patients.

Women presenting with epithelial ovarian cancer should be treated in centers with both aggressive surgical and chemotherapy teams prepared to confront the modifiable factors, which can optimize the patient's outcome. This implies experience in extensive cytoreductive surgery, including the removal of the tumor from the upper abdomen. An intraperitoneal (IP) catheter should be left in place for the consideration of IP chemotherapy. The supportive care structures need to be in place with teams prepared to help women complete six cycles of intravenous and IP paclitaxel (Taxol) and IP cisplatin with the least toxicity. Survival figures of 128 months are to be expected when no residual disease is left behind and IP chemotherapy is administered successfully.

Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

BACKGROUND: Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied. METHODS: In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology. RESULTS: Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression. CONCLUSION: Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.

The successful use of cardiopulmonary support for a transected bronchus.

A 20-year-old male was involved in a motor vehicle accident and computed tomography revealed a completely transected right mainstem bronchus. An Emergency Department (ED) right anterior thoracotomy was necessary soon after arrival at our institution secondary to acute desaturation that was unresponsive to ventilator and chest tube management. This allowed direct intubation and ventilation of the right middle and lower lobes directly through the thoracotomy incision, which stabilized the patient for transport to the operating room. Once there, percutaneous cardiopulmonary support (CPS) was initiated to allow primary surgical repair of the transected bronchus. Post surgery, the patient was transported to the surgical intensive care unit on CPS which he required for an additional two days. The patient eventually did well and was discharged home. To our knowledge this is the first successful reported case of using the Avalon Elite dual lumen veno-venous cannula for CPS in a patient with complete right main-stem bronchus transection and bilateral pulmonary contusions.

Do uterine risk factors or lymph node metastasis more significantly affect recurrence in patients with endometrioid adenocarcinoma?

OBJECTIVES: Controversy continues over the importance of lymph node (LN) status in treating and predicting recurrence in endometrial cancer. Several predictive models are available which use uterine factors to stratify risk groups. Our objective was to determine how LN status affects recurrence and survival compared to uterine factors alone. METHODS: A retrospective review was performed of patients undergoing complete surgical staging for clinical stage 1 endometrioid adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high intermediate risk (H-IR) criteria (2 factors : age>60, grade 3, >50% DOI), GOG-99 H-IR criteria (age >70+1 factor, age 50-70+2 factors, any age +3 factors: grade 2 or 3, LVSI, >50% DOI), and PORTEC 2 criteria. Rates of nodal involvement, recurrence rates, PFS, and OS were compared. RESULTS: We identified 352 clinical stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1 eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among groups (18.4% vs 19.7%, p=0.83) but recurrence rates were dissimilar (7.4% vs 27.3%, p=0.0004). Only 93 met PORTEC 2 criteria for treatment with no association between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR group compared to GOG-99 eligible (34.6% vs 16.3%, p=0.0004, 28.3% vs. 10.6%, p=0.0002). CONCLUSIONS: Patients with H-IR disease based on uterine characteristics alone have substantial risk of nodal involvement. Knowledge of LN status may better define risk, prognosis, and postoperative treatment.

Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study.

BACKGROUND: High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells. METHODS: Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen. RESULTS: Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH). CONCLUSION: The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.

The epidemiology of fractures in adolescents with reference to social deprivation.

A relationship between social deprivation and the incidence of fracture in adolescents has not previously been shown. We have used a complete fracture database to identify adolescents who sustained fractures in 2000. The 2001 Scottish census was used to obtain age-specific population and deprivation data according to the Carstairs score. Regression analysis determined the relationship between the incidence of fractures and social deprivation. We analysed 1574 adolescents with fractures (1083 male, 491 female). The incidence of fractures in this group was 21.8 per thousand (31.0 male, 13.1 female). Social deprivation predicted the incidence in adolescent males and females. The incidence of fractures of the proximal upper limb and distal radius in females was overwhelmingly influenced by socioeconomic factors. Males of 15 to 20 years of age were more likely to sustain fractures of the hand and carpus if they lived in economically depressed neighbourhoods.

Evaluation of linear array human papillomavirus genotyping using automatic optical imaging software.

Variations in biological behavior suggest that each carcinogenic human papillomavirus (HPV) type should be considered individually in etiologic studies. HPV genotyping assays might have clinical applications if they are approved for use by the FDA. A widely used genotyping assay is the Roche Linear Array HPV genotyping test (LA). We used LA to genotype the HPV isolates from cervical specimens from women with the full spectrum of cervical disease: cervical cancer, cervical intraepithelial neoplasia (CIN), and HPV infections. To explore the feasibility and value of the automated reading of the LA results, we custom-designed novel, optical imaging software that provides optical density measurements of LA bands. We compared unmagnified visual examination with the automated measurements. The two measurements were highly associated. By either method, the threshold between a negative and a positive result was fairly sharp, with a clear bimodal distribution. Visually, most positive results were judged to be strong or medium, with fewer equivocal results categorized as weak (9.5% of positive samples), very weak (6.5% of positive samples), or extremely weak (7.7% of positive samples). The automated measurements of the intensities were significantly associated with the strength of the visual categories (P < 0.001). At the extremes of the automated signal intensities (< or = 20 units or > or = 120 units), the bands were almost always categorized visually as negative and positive, respectively. In the equivocal zone (20 to 119 units), specimens were more increasingly likely to be judged to be visually positive as the number of other, definite infections on the same strip increased (P for trend < 0.001). Multiple, concurrent infections comprise > or = 25% of HPV infections; thus, any systematic visual tendency that influences their evaluation when the result is equivocal should be minimized. Therefore, automated reading is probably worth development if easy-to-calibrate hardware and software can be optimized.