An exploration of adolescent facial shape changes with age via multilevel partial least squares regression.

BACKGROUND AND OBJECTIVES: Multilevel statistical models represent the existence of hierarchies or clustering within populations of subjects (or shapes in this work). This is a distinct advantage over single-level methods that do not. Multilevel partial-least squares regression (mPLSR) is used here to study facial shape changes with age during adolescence in Welsh and Finnish samples comprising males and females. METHODS: 3D facial images were obtained for Welsh and Finnish male and female subjects at multiple ages from 12 to 17 years old. 1000 3D points were defined regularly for each shape by using "meshmonk" software. A three-level model was used here, including level 1 (sex/ethnicity); level 2, all "subject" variations excluding sex, ethnicity, and age; and level 3, age. The mathematical formalism of mPLSR is given in an Appendix. RESULTS: Differences in facial shape between the ages of 12 and 17 predicted by mPLSR agree well with previous results of multilevel principal components analysis (mPCA); buccal fat is reduced with increasing age and features such as the nose, brow, and chin become larger and more distinct. Differences due to ethnicity and sex are also observed. Plausible simulated faces are predicted from the model for different ages, sexes and ethnicities. Our models provide good representations of the shape data by consideration of appropriate measures of model fit (RMSE and R2). CONCLUSIONS: Repeat measures in our dataset for the same subject at different ages can only be modelled indirectly at the lowest level of the model at discrete ages via mPCA. By contrast, mPLSR models age explicitly as a continuous covariate, which is a strong advantage of mPLSR over mPCA. These investigations demonstrate that multivariate multilevel methods such as mPLSR can be used to describe such age-related changes for dense 3D point data. mPLSR might be of much use in future for the prediction of facial shapes for missing persons at specific ages or for simulating shapes for syndromes that affect facial shape in new subject populations.

Systematic molecular and clinical analysis of uterine leiomyomas from fertile-aged women undergoing myomectomy.

STUDY QUESTION: What are the distributions and associated clinical characteristics of mediator complex subunit 12 (MED12), high mobility group AT-hook 2 (HMGA2) and fumarate hydratase (FH) aberrations in uterine leiomyomas from fertile-aged myomectomy patients? SUMMARY ANSWER: These driver mutations account for the majority (83%) of tumours in fertile-aged patients. WHAT IS KNOWN ALREADY: Alterations affecting MED12, HMGA2 and FH account for 80-90% of uterine leiomyomas from middle-aged hysterectomy patients, while the molecular background of tumours from young myomectomy patients has not been systematically studied. STUDY DESIGN, SIZE, DURATION: A retrospective series of 361 archival uterine leiomyoma samples from 234 women aged ≤45 years undergoing myomectomy in 2009-2014 was examined. Associations between the molecular data and detailed clinical information of the patients and tumours were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples and MED12 exons 1 and 2 were sequenced to identify mutations. Level of HMGA2 expression was evaluated by immunohistochemistry. Biallelic FH inactivation was analysed with 2-succinylcysteine staining, which is an indirect method of assessing FH deficiency. All patients' medical histories were reviewed, and clinical information of patients and tumours was combined with molecular data. MAIN RESULTS AND THE ROLE OF CHANCE: The median age at operation was 34 years. The majority (58%) of patients were operated on for a single leiomyoma. Known driver mutations were identified in 83% of tumours (71% MED12; 9% HMGA2; 3% FH). In solitary leiomyomas, the MED12 mutation frequency was only 43%, and 29% were wild-type for all driver alterations. MED12 mutations were associated with multiple tumours, smaller tumour size and subserosal location. LIMITATIONS, REASONS FOR CAUTION: Although comprehensive, the study is retrospective in nature and all samples have been collected for routine diagnostic purposes. The use of paraffin-embedded samples and immunohistochemistry may have led to an underestimation of mutations. Due to the limited sample size and rarity of especially FH-deficient leiomyomas, the data are partly descriptive. WIDER IMPLICATIONS OF THE FINDINGS: The contribution of driver mutations in leiomyomas from young myomectomy patients is comparable to tumours obtained from hysterectomies of mostly middle-aged women. Our results support the earlier findings that MED12 mutations are associated with multiple tumours, smaller tumour size and subserosal location. The study emphasizes the distinct molecular background of solitary leiomyomas, and more research is needed to clarify the underlying causes of the notable proportion of wild-type leiomyomas. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Academy of Finland (307773), the Sigrid Jusélius Foundation, the Cancer Foundation Finland and the iCAN Digital Precision Cancer Medicine Flagship. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Multilevel principal components analysis of three-dimensional facial growth in adolescents.

BACKGROUND AND OBJECTIVES: The study of age-related facial shape changes across different populations and sexes requires new multivariate tools to disentangle different sources of variations present in 3D facial images. Here we wish to use a multivariate technique called multilevel principal components analysis (mPCA) to study three-dimensional facial growth in adolescents. METHODS: These facial shapes were captured for Welsh and Finnish subjects (both male and female) at multiple ages from 12 to 17 years old (i.e., repeated-measures data). 1000 "dense" 3D points were defined regularly for each shape by using a deformable template via "meshmonk" software. A three-level model was used here, namely: level 1 (sex/ethnicity); level 2, all "subject" variations excluding sex, ethnicity, and age; and level 3, age. The technicalities underpinning the mPCA method are presented in Appendices. RESULTS: Eigenvalues via mPCA predicted that: level 1 (ethnicity/sex) contained 7.9% of variation; level 2 contained 71.5%; and level 3 (age) contained 20.6%. The results for the eigenvalues via mPCA followed a similar pattern to those results of single-level PCA. Results for modes of variation made sense, where effects due to ethnicity, sex, and age were reflected in modes at appropriate levels of the model. Standardised scores at level 1 via mPCA showed much stronger differentiation between sex and ethnicity groups than results of single-level PCA. Results for standardised scores from both single-level PCA and mPCA at level 3 indicated that females had different average "trajectories" with respect to these scores than males, which suggests that facial shape matures in different ways for males and females. No strong evidence of differences in growth patterns between Finnish and Welsh subjects was observed. CONCLUSIONS: mPCA results agree with existing research relating to the general process of facial changes in adolescents with respect to age quoted in the literature. They support previous evidence that suggests that males demonstrate larger changes and for a longer period of time compared to females, especially in the lower third of the face. These calculations are therefore an excellent initial test that multivariate multilevel methods such as mPCA can be used to describe such age-related changes for "dense" 3D point data.

3D follow-up study of facial asymmetry after developmental dysplasia of the hip.

OBJECTIVES: To evaluate the change in facial asymmetry among subjects treated for developmental dysplasia of the hip (DDH) from childhood to adolescence. SETTING AND SAMPLE POPULATION: A total of 39 adolescents (26 females and 13 males), born and treated for DDH during 1997-2001, participated in the first examination in 2007 (T1; at the age of 8.2) and in the follow-up in 2016 (T2; at the age of 16.6). MATERIAL AND METHODS: In this longitudinal study, three-dimensional (3D) images were taken using a 3DMD face system based on a stereophotogrammetric method. Facial asymmetry was determined as the average distance (mm) calculated between the original and superimposed mirrored face and the symmetry percentage (%) calculated as the face area where the distance between the original face and the mirrored surface does not exceed 0.5 mm. RESULTS: Results showed increased asymmetry from T1 to T2. The average distance increased for whole face (from 0.51 mm to 0.59 mm, P = .001), upper face (from 0.41 mm to 0.49 mm, P = .005), mid-face (from 0.48 mm to 0.57, P = .002) and lower face (from 0.74 mm to 0.85 mm, P = .147). Facial symmetry percentage decreased for whole face from 61.23% to 55.38% (P = .011), for upper face from 69.27% to 62.24% (P = .005) and for mid-face from 62.29% to 55.63% (P = .007) and for lower face from 43.37% to 42.19% (P = .66). CONCLUSION: Facial asymmetry increases from childhood to adulthood in subjects treated for DDH. Orthodontic treatment does not eliminate this asymmetric facial growth.

The association of the HLA-A*24:02, B*39:01 and B*39:06 alleles with type 1 diabetes is restricted to specific HLA-DR/DQ haplotypes in Finns.

BACKGROUND: We analysed the previously reported association of the HLA-A*24:02, B*18 and B*39 alleles with type 1 diabetes and diabetes associated autoimmunity in the Finnish population applying HLA-DR/DQ stratification. MATERIALS & METHODS: Haplotype transmission was analysed in 2424 nuclear families from the Finnish Paediatric Diabetes Register. Survival analysis was applied to study the development of islet autoantibodies and further progression to clinical diabetes in the prospective follow-up cohort from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. The subjects were genotyped for specific HLA class I alleles by sequence-specific hybridization using lanthanide labelled nucleotide probes. RESULTS: The HLA-B*39:06 allele was found almost exclusively on the (DR8)-DQB1*04 haplotype in which its presence changed the disease risk status of the whole haplotype from neutral to predisposing. The HLA-A*24:02 and the B*39:01 alleles increased the diabetes-associated risk of the DRB1*04:04-DQA1*03-DQB1*03:02 haplotype but the alleles were in linkage disequilibrium and no independent effect could be detected. Within the DIPP cohort, neither the A*24:02 nor the B*39:01 allele were associated with seroconversion but were in contrast associated with increased progression from seroconversion to clinical disease. DISCUSSION & CONCLUSIONS: The independent predisposing effect of the HLA-B*39:06 allele with type 1 diabetes was confirmed in the Finnish population but the association of the A*24:02 and B*39:01 alleles remained inconclusive whilst both A*24:02 and B*39:01 affected the progression rate from seroconversion to autoantibody positivity to overt type 1 diabetes.

Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children.

Some studies have assessed the efficacy of influenza vaccination in children separately for moderate-to-severe and any influenza, but the definition used for identifying children with moderate-to-severe illness has not been validated. We analyzed clinical and socioeconomic data from two prospective cohort studies of respiratory infections among children aged ≤13 years (four influenza seasons, 3,416 child-seasons of follow-up). We categorized children with laboratory-confirmed influenza into two mutually exclusive groups of moderate-to-severe and mild influenza using the previously proposed criteria. We obtained the data for the analyses from structured medical records filled out by the study physicians and from daily symptom cards filled out by the parents. Of 434 cases of influenza, 217 (50 %) were classified as moderate-to-severe and 217 (50 %) as mild. The mean duration of fever was 4.0 days in children with moderate-to-severe influenza and 3.1 days in those with milder illness (P < 0.0001). Antibiotics were prescribed to 111 (51 %) children with moderate-to-severe and to ten (5 %) children with mild influenza (P < 0.0001). The rates of parental work absenteeism were 184 days per 100 children with moderate-to-severe influenza and 135 days per 100 children with mild influenza (P = 0.02). The corresponding rates of children's own absenteeism from day care or school were 297 and 233 days respectively per 100 children (P = 0.006). Categorization of children into groups with moderate-to-severe and mild influenza is meaningful, and it identifies children in whom the clinical and socioeconomic impact of influenza is highest. Illness severity should be considered when assessing influenza vaccine effectiveness in children.

Primary tooth size asymmetry in twins and singletons.

OBJECTIVES: To explore asymmetry values of antimeric deciduous tooth crown dimensions in three types of twins: monozygotic (MZ), dizygotic same-sex (DZ) and opposite-sex (OS) vs. single-born controls. SETTING AND SAMPLE POPULATION: Mesiodistal and labio-lingual crown dimensions of second deciduous molars and mesiodistal canine and first molar crown dimensions of 2159 children at 6-12 years of age were evaluated, originating from the US cross-sectional Collaborative Perinatal Study from the 1970s, including altogether MZ (n = 28), DZ same-sex (n = 33) and OS (n = 39) pairs. Single born (n = 1959) were used as controls. MATERIAL AND METHODS: Dental casts were measured for comparison of variance relationships calculated from antimeric teeth, exhibiting fluctuating (FA), and directional (DA) asymmetry using anova. RESULTS: Significant differences appeared in MZ and OS girls in DA of deciduous canines, which gain size in the first and second trimester, and deciduous second molars, which finally stop crown growth during the early post-natal period. Significantly, increased FA values appeared for lower deciduous canines and second molars, indicating greatest environmental stress in OS girls, MZ girls and DZ boys. Twin girls had more fluctuating and directional crown asymmetry than twin boys, but in some dimensions, the twins were more symmetric than controls. CONCLUSIONS: Transmembrane hormonal influence between opposite-sex twins, and late gestational stress factors, caused by placental malfunction and/or monochorionicity, may be involved in asymmetric growth of antimers, during critical periods of crown size gain.

Update with level 1 studies of the European Hernia Society guidelines on the treatment of inguinal hernia in adult patients.

PURPOSE: In 2009, the European Hernia Society published the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients. The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare. The guidelines expired January 1, 2012. To keep them updated, a revision of the guidelines was planned including new level 1 evidence. METHODS: The original Oxford Centre for Evidence-Based Medicine ranking was used. All relevant level 1A and level 1B literature from May 2008 to June 2010 was searched (Medline and Cochrane) by the Working Group members. All chapters were attributed to the two responsible authors in the initial guidelines document. One new chapter on fixation techniques was added. The quality was assessed by the Working Group members during a 2-day meeting and the data were analysed, especially with respect to any change in the level and/or text of any of the conclusions or recommendations of the initial guidelines. In the end, all relevant references published until January 1, 2013 were included. The final text was approved by all Working Group members. RESULTS: For the following topics, the conclusions and/or recommendations have been changed: indications for treatment, treatment of inguinal hernia, day surgery, antibiotic prophylaxis, training, postoperative pain control and chronic pain. The addendum contains all current level 1 conclusions, Grade A recommendations and new Grade B recommendations based on new level 1 evidence (with the changes in bold). CONCLUSIONS: Despite the fact that the Working Group responsible for it tried to represent most kinds of surgeons treating inguinal hernias, such general guidelines inevitably must be fitted to the daily practice of every individual surgeon treating his/her patients. There is no doubt that the future of guideline implementation will strongly depend on the development of easy to use decision support algorithms tailored to the individual patient and on evaluating the effect of guideline implementation on surgical outcome. At the 35th International Congress of the EHS in Gdansk, Poland (May 12-15, 2013), it was decided that the EHS, IEHS and EAES will collaborate from now on with the final goal to publish new joint guidelines, most likely in 2015.

Long term water storage deteriorates bonding of composite resin to alumina and zirconia short communication.

Objective of this study was to evaluate the effects of long term water storage and ageing on the bond strength of resin composite cement to yttria-stabilized zirconium dioxide (zirconia) and dialuminium trioxide (alumina). Substrate specimens of alumina and zirconia were air particle abraded with dialuminium trioxide before priming and application of composite resin. Priming was made with gamma metharyloxy-trimethoxysilane or acryloxypropyl-trimethoxysilane monomer after which the intermediate dimethacrylate resin was applied and photopolymerized. This was followed by curing particulate composite resin cement (Relyx ARC) to the substrate as a resin stub. The ageing methods of the specimens (n=6) were: (1) they stored four years in 37±1ºC distilled water, (2) thermocycled 8000 times between 55±1ºC and 5±1ºC, (3) stored first in water for four years and then thermocycled. Specimens which were stored dry, were used as controls. Bonding of composite resin was measured by shear-bond strength test set-up. Both thermocycling and long-term water storage decreased significantly shear bond strength values compared to the control group (from the level of 20 MPa to 5 MPa) regardless of the used primer or the type of the substrate. Combination of four years water storage and thermocyling reduced the bond strength even more, to the level of two to three megapascals. In can be concluded that water storage and thermocycling itselves, and especially combination of water storage and thermocycling can cause considerable reduction in the bond strength of composite resin cement to alumina and zirconia.

Overabundant FANCD2, alone and combined with NQO1, is a sensitive marker of adverse prognosis in breast cancer.

BACKGROUND: Defective DNA repair is central to the progression and treatment of breast cancer. Immunohistochemically detected DNA repair markers may be good candidates for novel prognostic and predictive factors that could guide the selection of individualized treatment strategies. PATIENTS AND METHODS: We have analyzed nuclear immunohistochemical staining of BRCA1, FANCD2, RAD51, XPF, and PAR in relation to clinicopathological and survival data among 1240 paraffin-embedded breast tumors, and additional gene expression microarray data from 76 tumors. The antioxidant enzyme NQO1 was analyzed as a potential modifier of prognostic DNA repair markers. RESULTS: RAD51 [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.70-0.94, P = 0.0050] and FANCD2 expression (HR 1.50, 95% CI 1.28-1.76, P = 1.50 × 10(-7)) were associated with breast cancer survival. High FANCD2 expression correlated with markers of adverse prognosis but remained independently prognostic in multivariate analysis (HR 1.27, 95% CI 1.08-1.49, P = 0.0043). The FANCD2-associated survival effect was most pronounced in hormone receptor positive, HER2-negative tumors, and in tumors with above-median NQO1 expression. In the NQO1-high subset, patients belonging to the highest quartile of FANCD2 immunohistochemical scores had a threefold increased risk of metastasis or death (HR 3.10, 95% CI 1.96-4.92). Global gene expression analysis indicated that FANCD protein overabundance is associated with the upregulation of proliferation-related genes and a downregulated nucleotide excision repair pathway. CONCLUSION: FANCD2 immunohistochemistry is a sensitive, independent prognostic factor in breast cancer, particularly when standard markers indicate relatively favorable prognosis. Taken together, our results suggest that the prognostic effect is linked to proliferation, DNA damage, and oxidative stress; simultaneous detection of FANCD2 and NQO1 provides additional prognostic value.

Signs and symptoms predicting influenza in children: a matched case-control analysis of prospectively collected clinical data.

We aimed to determine whether there are signs or symptoms that could help clinicians to distinguish between influenza and other respiratory infections. The clinical data for this matched case-control analysis were derived from a 2-year prospective cohort study of respiratory infections among children aged≤13 years. At any signs of respiratory infection, the children were examined and nasal swabs were obtained for virologic analyses. Cases were 353 children with laboratory-confirmed influenza and controls were 353 children with respiratory symptoms who tested negative for influenza. Cases and controls were matched for gender, age, and timing of the visit. In the multivariate conditional logistic regression analyses, fever was the only sign that independently predicted influenza virus infection, with odds ratios ranging from 13.55 (95% confidence interval [CI], 6.90-26.63) to 50.10 (95% CI, 16.25-154.45), depending on the degree of fever. In all analyses, the predictive capability of fever increased with incremental elevations in the child's temperature. The likelihood ratio of fever≥40.0°C in predicting influenza was 6.00 (95% CI, 2.80-12.96). Among unselected children seen as outpatients during influenza outbreaks, fever is the only reliable predictor of influenza virus infection. The optimal use of influenza-specific antiviral drugs in children may require virologic confirmation.

Admission diagnoses of children 0-16 years of age hospitalized with influenza.

The prompt diagnosis of influenza enables the institution of antiviral therapy and adequate cohorting of patients, but scarce data are available to help clinicians correctly suspect influenza in children at the time of admission. This 16-year retrospective study assessed the main admission diagnoses of 401 children aged ≤16 years hospitalized with virologically confirmed influenza. The clinical data were derived from a systematic review of the medical records of the children. Sepsis-like illness was the main reason for admission in 52% of infants aged <6 months and in 7-16% of the older children. Respiratory symptoms accounted for 38% of admissions, and 15% of children were hospitalized due to acute neurologic conditions, primarily febrile convulsions. Wheezing or exacerbation of asthma was the primary reason for admission in 14% of children aged <3 years. No differences were observed in the admission diagnoses between children with influenza A and B infections. The main admission diagnoses vary widely in different age groups of children with influenza, and only a minority of children are hospitalized for respiratory symptoms. The leading role of sepsis-like illness in infants aged <6 months calls for increased efforts to find protective measures against influenza in this age group.

Smoking and the outcome of infection.

Smoking has substantial local and systemic adverse effects on the immune system, respiratory tract and skin and soft tissues. Smokers are at increased risk of invasive pneumococcal disease, pneumonia, periodontitis, surgical infections, tuberculosis, influenza and meningococcal disease. The results of several studies indicate that smokers with periodontitis or tuberculosis suffer more severe disease. Data on the impact of smoking on sepsis and pneumonia are controversial and limited, and systematic data regarding the outcome of the majority of infections in smokers are scarce. Abundant data indicate that children exposed to environmental tobacco smoke (ETS) suffer from more severe infections. However, information regarding the effects of ETS on the outcome of infections in adults is limited. Various aspects of the relation between smoking and the outcome of bacterial infection (e.g. potential dose-dependent effects and the interactions between smoking and other environmental factors that may affect the course of infectious diseases) remain to be established.

Feasibility of diagnosing influenza within 24 hours of symptom onset in children 1-3 years of age.

Diagnosing influenza at an early stage of illness is important for the initiation of effective antiviral treatment. However, especially in young children, influenza often commences with an abrupt onset of fever, with full-blown respiratory symptoms developing only later. We determined the feasibility of diagnosing influenza in young children already during the first signs of the illness. During confirmed influenza activity, we obtained nasal swabs from children aged 1-3 years who presented as outpatients within 24 hours of the onset of fever (≥38.0°C). The specimens were tested for influenza viruses with viral culture, antigen detection, PCR, and a rapid point-of-care test (Actim Influenza A&B, Medix Biochemica, Finland). In addition, follow-up specimens were obtained from a proportion of children 3-7 days later. Influenza virus was detected already within 24 hours of symptom onset in 56 of 61 (92%; 95% CI 82-97%) children in whom influenza was eventually confirmed in the laboratory. A total of 158 rapid tests performed within 24 hours of symptom onset yielded a sensitivity of 90% (95% CI 74-98%) for influenza A viruses but only 25% (95% CI 3-61%) for influenza B viruses (P < 0.001), resulting in an overall sensitivity of 77% (95% CI 61-89%) and specificity of 99% (95% CI 95-100%) for all influenza viruses. In most young children, influenza can already be accurately diagnosed within 24 hours of symptom onset. The rapid point-of-care test used was sensitive and specific for diagnosing influenza A, but its sensitivity for influenza B was limited.

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA).

BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

European Hernia Society guidelines on the treatment of inguinal hernia in adult patients.

The European Hernia Society (EHS) is proud to present the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients. The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare. They have been developed by a Working Group consisting of expert surgeons with representatives of 14 country members of the EHS. They are evidence-based and, when necessary, a consensus was reached among all members. The Guidelines have been reviewed by a Steering Committee. Before finalisation, feedback from different national hernia societies was obtained. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) instrument was used by the Cochrane Association to validate the Guidelines. The Guidelines can be used to adjust local protocols, for training purposes and quality control. They will be revised in 2012 in order to keep them updated. In between revisions, it is the intention of the Working Group to provide every year, during the EHS annual congress, a short update of new high-level evidence (randomised controlled trials [RCTs] and meta-analyses). Developing guidelines leads to questions that remain to be answered by specific research. Therefore, we provide recommendations for further research that can be performed to raise the level of evidence concerning certain aspects of inguinal hernia treatment. In addition, a short summary, specifically for the general practitioner, is given. In order to increase the practical use of the Guidelines by consultants and residents, more details on the most important surgical techniques, local infiltration anaesthesia and a patient information sheet is provided. The most important challenge now will be the implementation of the Guidelines in daily surgical practice. This remains an important task for the EHS. The establishment of an EHS school for teaching inguinal hernia repair surgical techniques, including tips and tricks from experts to overcome the learning curve (especially in endoscopic repair), will be the next step. Working together on this project was a great learning experience, and it was worthwhile and fun. Cultural differences between members were easily overcome by educating each other, respecting different views and always coming back to the principles of evidence-based medicine. The members of the Working Group would like to thank the EHS board for their support and especially Ethicon for sponsoring the many meetings that were needed to finalise such an ambitious project.

Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up.

BACKGROUND: Recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non-RSV bronchiolitis. METHODS: We identified retrospectively all children <2 years of age who were admitted to Turku University Hospital because of bronchiolitis in the months of August-December during 1988-2001. The primary outcome was recurrent wheezing that required long-term asthma medication. Data on asthma medications of the individual children were derived from the Social Insurance Institution of Finland. RESULTS: Within the first year after hospitalization, 36 of 217 (16.6%) children with non-RSV bronchiolitis developed recurrent wheezing, compared with five of 199 (2.5%) children with RSV bronchiolitis [relative risk (RR) 6.6; 95% confidence interval (CI) 2.6-16.5]. The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years (RR 2.9; 95% CI 1.7-5.1) and 3 years (RR 3.4; 95% CI 2.0-5.7) after hospitalization. The increased risk of recurrent wheezing in children with non-RSV-associated bronchiolitis was observed both in boys and girls at all time points of the 3-year follow-up, and it was not explained by the age difference between the RSV and non-RSV groups or any confounding seasonal factors. CONCLUSION: Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis.

Functional comparison of the dynamic hip screw and the Gamma locking nail in trochanteric hip fractures: a matched-pair study of 268 patients.

The aim of this prospective matched-pair (age, sex, fracture type, residential status, and walking ability at fracture) study was to analyse the short-term outcome after Gamma nail (GN) and dynamic hip screw (DHS) fixation, focusing especially on functional aspects (Standardised Audit of Hip Fractures in Europe [SAHFE] hip fracture follow-up forms), reoperations, and mortality. Both groups consisted of 134 patients. DHS and GN groups did not differ significantly with respect to location of residence at 4 months or returning to the prefracture dwelling (78% vs. 73%, P = 0.224). The change in walking ability at 4 months compared to prefracture situation was better in the DHS group (p = 0.042), although there was no difference in the change of use of walking aids. The frequency of reoperations during the first year was somewhat lower in the DHS group (8.2% vs. 12.7%, p = 0.318). Mortality was lower in the DHS group both at 4 months (6.0% vs. 13.4%, p = 0.061) and 12 months (14.9% vs. 23.9%, p = 0.044). Although walking ability was better and mortality lower in the DHS group, both methods are useful in the treatment of trochanteric femoral fractures.

An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers.

The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.

Influence of adenosine triphosphate and ABCB1 (MDR1) genotype on the P-glycoprotein-dependent transfer of saquinavir in the dually perfused human placenta.

BACKGROUND: The ATP-dependent drug-efflux pump, P-glycoprotein (P-gp) encoded by ABCB1 (MDR1), plays a crucial role in several tissues forming blood-tissue barriers. Absence of a normally functioning P-gp can lead to a highly increased tissue penetration of a number of clinically important drugs. METHODS: We have studied the dose-response effect of exogenous ATP on the placental transfer of the well-established P-gp substrate saquinavir in 17 dually perfused human term placentas. We have also studied the influence of the ABCB1 polymorphisms 2677G>T/A and 3435C>T on placental P-gp expression (n = 44) and the transfer (n = 16) of saquinavir. RESULTS: The present results indicate that the addition of exogenous ATP to the perfusion medium does not affect the function of P-gp as measured by saquinavir transfer across the human placenta. The variant allele 3435T was associated with significantly higher placental P-gp expression than the wild-type alleles. However, neither polymorphism affected placental transfer of saquinavir nor there was any correlation between P-gp expression and saquinavir transfer. CONCLUSIONS: Our results indicate that addition of exogenous ATP is not required for ATP-dependent transporter function in a dually perfused human placenta. Although the ABCB1 polymorphism 3435C>T altered the expression levels of P-gp in the human placenta, this did not have any consequences on P-gp-mediated placental transfer of saquinavir.