'Your hopes can run away with your realistic expectations': a qualitative study of women and men's decision-making when undergoing multiple cycles of IVF.

STUDY QUESTION: What are the factors that contribute to the decision to continue or stop IVF treatment after multiple unsuccessful cycles? SUMMARY ANSWER: Factors contributing to the decision included external factors, such as their doctor's guidance, success rates, the outcomes of previous cycles and anecdotal stories of success, as well as emotional and cognitive drivers, including perception of success, hope and fear of regret. WHAT IS KNOWN ALREADY: Infertility affects about one in six Australian couples of reproductive age. Regarding IVF, some couples with a good prognosis drop out of treatment prematurely, whilst others continue for multiple cycles, despite limited chances of success. Little is known about what factors contribute to the decision to continue IVF after multiple failed cycles. STUDY DESIGN SIZE DURATION: Semi-structured face-to-face and telephone interviews were conducted with 22 participants. Interviews were audio-recorded, transcribed and analysed thematically using Framework analysis. PARTICIPANTS/MATERIALS SETTING METHODS: Doctors and nurses at an Australian private fertility clinic recruited individuals and/or couples who had undergone three or more complete unsuccessful cycles of IVF. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of participants had decided to or were leaning towards continuing treatment. Participants expressed a range of common factors important in their decision-making, which were evident both within and across couples. For most, their doctor's advice and hope were key factors influencing their decision. Most participants expressed they would continue as long as there was a chance of success and until their doctor advised otherwise. Other factors included participants' perception of their likelihood of success, hearing anecdotal stories of success after multiple cycles, positive outcomes of previous cycles and fear of regret. LIMITATIONS REASONS FOR CAUTION: The sample was highly educated and recruited from one private Australian fertility clinic only. Many participants were also couples, which may have resulted in more homogenous data as they shared the same diagnosis for infertility and outcomes of previous cycles. Factors influencing the decision to continue or stop may differ in different sociodemographic populations and in other healthcare systems. WIDER IMPLICATIONS OF THE FINDINGS: Given the important role of the doctor's guidance and patients' own perceptions of their likelihood of success, which they tended to overestimate, it is vital that fertility specialists give accurate and transparent information regarding their likelihood of success and continue to regularly communicate this throughout the IVF journey. Anecdotal stories of success against the odds appeared to be influential in the decision to continue and underpinned unrealistic perceptions of possible success. More personalized, cumulative estimates of likelihood of success may help couples with their decision-making as well as with discussions about ending treatment or setting a limit before commencing IVF. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the National Health and Medical Research Council (NHMRC) Program Grant (APP1113532). No further competing interests exist.

Physical inactivity and knee osteoarthritis in guinea pigs.

OBJECTIVE: To investigate whether and how a sedentary lifestyle contributes to knee osteoarthritis (OA) incidence and severity. DESIGN: An experiment was conducted using Hartley guinea pigs, an established idiopathic knee OA model. To simulate a sedentary lifestyle, growing animals (n = 18) were housed for 22 weeks in small cages that restricted their mobility, while another group of animals (n = 17) received daily treadmill exercise to simulate moderate physical activity. After the experiment, histological assessments, biochemical assays, and mechanical testing were conducted to compare tibial articular cartilage structure, strength, and degree of OA degeneration between sedentary and physically active animals. Groups were also compared based on body weight and composition, as well as gut microbial community composition assessed using fecal 16S rRNA gene sequencing. RESULTS: Prevalence of knee OA was similar between sedentary and physically active animals, but severity of the disease (cartilage lesion depth) was substantially greater in the sedentary group (P = 0.02). In addition, during the experiment, sedentary animals developed cartilage with lower aggrecan quantity (P = 0.03) and accumulated more body weight (P = 0.005) and visceral adiposity (P = 0.007). Groups did not differ greatly, however, in terms of cartilage thickness, collagen quantity, or stiffness, nor in terms of muscle weight, subcutaneous adiposity, or gut microbial community composition. CONCLUSIONS: Our findings indicate that a sedentary lifestyle promotes the development of knee OA, particularly by enhancing disease severity rather than risk of onset, and this potentially occurs through multiple pathways including by engendering growth of functionally deficient joint tissues and the accumulation of excess body weight and adiposity.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

A constitutive description of the anisotropic response of the fascia lata.

In this paper we propose a constitutive model to analyze in-plane extension of goat fascia lata. We first perform a histological analysis of the fascia that shows a well-organized bi-layered arrangement of undulated collagen fascicles oriented along two well defined directions. To develop a model consistent with the tissue structure we identify the absolute and relative thickness of each layer and the orientation of the preferred directions. New data are presented showing the mechanical response in uniaxial and planar biaxial extension. The paper proposes a constitutive relation to describe the mechanical response. We provide a summary of the main ingredients of the nonlinear theory of elasticity and introduce a suitable strain-energy function to describe the anisotropic response of the fascia. We validate the model by showing good fit of the numerical results and the experimental data. Comments are included about differences and analogies between goat fascia lata and the human iliotibial band.

Exploratory bioinformatics study of lncRNAs in Alzheimer's disease mRNA sequences with application to drug development.

Long noncoding RNA (lncRNA) within mRNA sequences of Alzheimer's disease genes, namely, APP, APOE, PSEN1, and PSEN2, has been analyzed using fractal dimension (FD) computation and correlation analysis. We examined lncRNA by comparing mRNA FD to corresponding coding DNA sequences (CDSs) FD. APP, APOE, and PSEN1 CDSs select slightly higher FDs compared to the mRNA, while PSEN2 CDSs FDs are lower. The correlation coefficient for these sequences is 0.969. A comparative study of differentially expressed MAPK signaling pathway lncRNAs in pancreatic cancer cells shows a correlation of 0.771. Selection of higher FD CDSs could indicate interaction of Alzheimer's gene products APP, APOE, and PSEN1. Including hypocretin sequences (where all CDSs have higher fractal dimensions than mRNA) in the APP, APOE, and PSEN1 sequence analyses improves correlation, but the inclusion of erythropoietin (where all CDSs have higher FD than mRNA) would suppress correlation, suggesting that HCRT, a hypothalamus neurotransmitter related to the wake/sleep cycle, might be better when compared to EPO, a glycoprotein hormone, for targeting Alzheimer's disease drug development. Fractal dimension and entropy correlation have provided supporting evidence, consistent with evolutionary studies, for using a zebrafish model together with a mouse model, in HCRT drug development.

Gene entropy-fractal dimension informatics with application to mouse-human translational medicine.

DNA informatics represented by Shannon entropy and fractal dimension have been used to form 2D maps of related genes in various mammals. The distance between points on these maps for corresponding mRNA sequences in different species is used to study evolution. By quantifying the similarity of genes between species, this distance might be indicated when studies on one species (mouse) would tend to be valid in the other (human). The hypothesis that a small distance from mouse to human could facilitate mouse to human translational medicine success is supported by the studied ESR-1, LMNA, Myc, and RNF4 sequences. ID1 and PLCZ1 have larger separation. The collinearity of displacement vectors is further analyzed with a regression model, and the ID1 result suggests a mouse-chimp-human translational medicine approach. Further inference was found in the tumor suppression gene, p53, with a new hypothesis of including the bovine PKM2 pathways for targeting the glycolysis preference in many types of cancerous cells, consistent with quantum metabolism models. The distance between mRNA and protein coding CDS is proposed as a measure of the pressure associated with noncoding processes. The Y-chromosome DYS14 in fetal micro chimerism that could offer protection from Alzheimer's disease is given as an example.

Dietary consistency and the midline sutures in growing pigs.

OBJECTIVES: The purpose of this study was to investigate the effects of reduced masticatory function on midline suture growth and morphology in growing pigs. SETTING AND SAMPLE POPULATION: The sample was 20 pigs separated into two dietary groups and raised at the Department of Anthropology, Harvard University. Midline suture specimens were analyzed at the Department of Orthodontics, University of Washington. MATERIALS AND METHODS: Ten farm pigs and 10 minipigs, all male, were randomly assigned to hard (n = 9) and soft-diet (n = 11) groups. Fluorochromic mineral labels were administered to document bone apposition, and the animals were killed after 12 weeks. Undecalcified sections of the interfrontal, interparietal, internasal, and intermaxillary sutures were evaluated for bone quantity and sutural thickness, interdigitation ratio and growth rate. RESULTS: Soft-diet pigs were characterized by a slower rate of weight gain and less bone than their hard-diet counterparts. Even after correction for weight gain, soft-diet pigs had reduced suture growth rate and thickness. However, no difference in interdigitation ratio was detected between dietary groups. CONCLUSIONS: Restriction to a soft diet reduces midline suture growth and bone apposition in the growing pig.

Pooled nasopharyngeal and oropharyngeal samples for the identification of respiratory viruses in adults.

A pooled sample of oropharyngeal swabs, nasopharyngeal swabs and nasopharyngeal washings, taken from each of 1,000 subjects, was compared to separate specimens from the same sampling. Multiplex real-time polymerase chain reaction (mqRT-PCR) was used to identify 12 respiratory viruses. Two hundred and forty-three (97%) of the 251 viruses identified in the separate samples were also identified in the mixed samples. The sensitivity rate was identical at 100% for all virus groups except coronaviruses. This sensitivity rate clearly justifies the use of pooled samples instead of separate samples for clinical and epidemiological purposes. The reduction in costs attained from the use of pooled samples may represent a critical advantage when considering its use in extensive clinical and epidemiological studies.

Peripubertal estrogen levels and physical activity affect femur geometry in young adult women.

UNLABELLED: The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. INTRODUCTION: It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. METHODS: We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. RESULTS: At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. CONCLUSIONS: This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.

Asia Pacific consensus recommendations for colorectal cancer screening.

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Control of jaw movements in two species of macropodines (Macropus eugenii and Macropus rufus).

The masticatory motor patterns of three tammar wallabies and two red kangaroos were determined by analyzing the pattern of electromyographic (EMG) activity of the jaw adductors and correlating it with lower jaw movements, as recorded by digital video and videoradiography. Transverse jaw movements were limited by the width of the upper incisal arcade. Molars engaged in food breakdown during two distinct occlusal phases characterized by abrupt changes in the direction of working-side hemimandible movement. Separate orthal (Phase I) and transverse (Phase II) trajectories were observed. The working-side lower jaw initially was drawn laterally by the balancing-side medial pterygoid and then orthally by overlapping activity in the balancing- and working-side temporalis and the balancing-side superficial masseter and medial pterygoid. Transverse movement occurred principally via the working-side medial pterygoid and superficial masseter. This pattern contrasted to that of placental herbivores, which are known to break down food when they move the working-side lower jaw transversely along a relatively longer linear path without changing direction during the power stroke. The placental trajectory results from overlapping activity in the working- and balancing-side adductor muscles, suggesting that macropods and placental herbivores have modified the primitive masticatory motor pattern in different ways.

Mixing of nasopharyngeal and oropharyngeal samples to identify potential respiratory pathogens in adults.

A mixed culture of oropharyngeal swabs, nasopharyngeal swabs and nasopharyngeal washings, taken from 400 patients, was compared to separate cultures of the same samples. The mixed culture identified Streptococcus pneumoniae in 37 of 40 (93%) patients with positive samples, Hemophilus influenzae in 28 of 29 (97%), and Moraxella catarrhalis in 94 of 94 (100%). These sensitivity rates clearly justify the use of mixed cultures instead of separate cultures for clinical and epidemiological purposes. The reduction in costs stemming from the use of mixed cultures may have a decisive influence when considering this test for extensive clinical and epidemiological purposes.

Epigenetic interactions and the structure of phenotypic variation in the cranium.

Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as the mammalian skull is a challenge because of the sheer complexity of the factors involved. We hypothesize that even in this complex system, the expression of phenotypic variation is structured by the interaction of a few key developmental processes. To test this hypothesis, we created a highly variable sample of crania using four mouse mutants and their wild-type controls from similar genetic backgrounds with developmental perturbations to particular cranial regions. Using geometric morphometric methods we compared patterns of size, shape, and integration in the sample within and between the basicranium, neurocranium, and face. The results highlight regular and predictable patterns of covariation among regions of the skull that presumably reflect the epigenetic influences of the genetic perturbations in the sample. Covariation between relative widths of adjoining regions is the most dominant factor, but there are other significant axes of covariation such as the relationship between neurocranial size and basicranial flexion. Although there are other sources of variation related to developmental perturbations not analyzed in this study, the patterns of covariation created by the epigenetic interactions evident in this sample may underlie larger scale evolutionary patterns in mammalian craniofacial form.

Risk factors for cardiopulmonary events during propofol-mediated upper endoscopy and colonoscopy.

BACKGROUND: Propofol-mediated sedation for endoscopy is popular because of its rapid onset and recovery profile. AIM: To examine procedure-specific occurrence and risk factors for cardiopulmonary events during propofol-mediated upper endoscopy (EGD) and colonoscopy. DESIGN: A cohort study using the Clinical Outcomes Research Initiative database was used to determine the frequency of cardiopulmonary events. Clinical Outcomes Research Initiative consisted of 69 practice sites comprising 593 US endoscopists. Multivariate logistic regression analysis used variables, such as age, ASA classification and propofol administration by monitored anaesthesia care or gastroenterologist-administered propofol to determine the risk of cardiopulmonary events. RESULTS: The overall cardiopulmonary event rate for 5928 EGDs and 11 683 colonoscopies was 11.7/1000 cases. For colonoscopy, ascending ASA classification was associated with an increased risk. Monitored anaesthesia care was associated with a decreased adjusted relative risk (0.5, 95% CI: 0.36-0.72). ASA I and II patients receiving monitored anaesthesia care for EGD exhibited a significantly lower relative risk (ARR 0.29, 95% CI: 0.14-0.64). For subjects with ASA class III or greater, there was no difference in the risk between monitored anaesthesia care and gastroenterologist-administered propofol. CONCLUSIONS: There are procedure-specific risk factors for cardiopulmonary events during propofol-mediated EGD and colonoscopy. These should be taken into account during future prospective comparative trials.

Trabecular bone in the bird knee responds with high sensitivity to changes in load orientation.

Wolff's law of trajectorial orientation proposes that trabecular struts align with the orientation of dominant compressive loads within a joint. Although widely considered in skeletal biology, Wolff's law has never been experimentally tested while controlling for ontogenetic stage, activity level, and species differences, all factors that may affect trabecular bone growth. Here we report an experimental test of Wolff's law using a within-species design in age-matched subjects experiencing physiologically normal levels of bone strain. Two age-matched groups of juvenile guinea fowl Numida meleagris ran on a treadmill set at either 0 degrees (Level group) or 20 degrees (Incline group), for 10 min per day over a 45-day treatment period. Birds running on the 20 degrees inclined treadmill used more-flexed knees than those in the Level group at midstance (the point of peak ground reaction force). This difference in joint posture enabled us to test the sensitivity of trabecular alignment to altered load orientation in the knee. Using a new radon transform-based method for measuring trabecular orientation, our analysis shows that the fine trabecular bone in the distal femur has a high degree of correspondence between changes in joint angle and trabecular orientation. The sensitivity of this response supports the prediction that trabecular bone adapts dynamically to the orientation of peak compressive forces.

Variation in practice of ileal intubation among diverse endoscopy settings: results from a national endoscopic database.

BACKGROUND: Terminal ileum intubation rates at colonoscopy are variable. One of the major indications for terminal ileum intubation is to identify Crohn's disease. Signs and symptoms which raise a suspicion of Crohn's include abdominal pain/bloating, anaemia and diarrhoea. AIM: To determine the proportion of terminal ileal intubation in patients undergoing evaluation of abdominal pain/bloating, anaemia or diarrhoea with normal endoscopic findings at colonoscopy. METHODS: The Clinical Outcomes Research Initiative national endoscopic database was analysed to determine the proportion of terminal ileum intubation in patients undergoing evaluation of either abdominal pain/bloating, anaemia or diarrhoea with normal endoscopic findings at colonoscopy and to characterize this population of patients. Patients with known or suspected inflammatory bowel disease were excluded from the analysis. RESULTS: Between January 2000 and December 2003, 21 638 patients underwent complete colonoscopy for evaluation of either abdominal pain/bloating, anaemia or diarrhoea with normal colon findings. Overall, 3858 patients (18%) underwent terminal ileum evaluation. Intubation rates differed according to procedure indication: abdominal pain (13%), anaemia (13%), diarrhoea (28%). Terminal ileum assessment declined with advancing patient age and was least frequent in Black patients (12% vs. 18% in non-Blacks, P < 0.0001). Ileal intubation rates also varied among endoscopy site types: community (17%), academic (21%), Veterans Affairs Medical Centres (17%), P < 0.0001. Multiple logistic regression identified patients with the indication of diarrhoea (OR: 2.58) as more likely to undergo terminal ileum intubation when compared with those with abdominal pain/bloating. Patients in Veterans Affairs (OR: 1.26) and academic (OR: 1.29) sites were more likely to undergo terminal ileum intubation compared with community sites. CONCLUSION: Less than one-fifth of patients with either abdominal pain/bloating, anaemia or diarrhoea underwent ileal intubation in the setting of a normal colonoscopy. Significant practice variation was observed in rates of terminal ileum evaluation. Further study is required to determine whether terminal ileum examination impacts patient management or outcome.

Review article: balancing the ideal versus the practical-considerations of colorectal cancer prevention and screening.

Colorectal cancer is responsible for over 500 000 deaths annually world-wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average- or high-risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.

Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women.

This 64-week prospective cohort trial evaluated the effects of 20-mg oestradiol implants, replaced every 4 months, in healthy postmenopausal women aged 45-65 years. Of 20 implant and 14 control subjects who remained in the trial at 32 weeks, 13 implant and seven controls continued to 64 weeks, with no baseline differences between completing and dropout subjects. At 64 weeks, implant subjects displayed increases of 5.4-7.6% in spine and hip bone mineral density ( p<0.05 versus controls). The abdominal fat-to-lean soft tissue ratio decreased by 18% in implant subjects ( p<0.001), but did not change in controls ( p<0.05 implants versus controls). Neither group displayed significant changes in weight, %fat or appendicular skeletal muscle mass. The 32-week data were consistent with these results. Hence, oestradiol implant therapy can reduce abdominal adiposity and could lower the risk of obesity-related metabolic disorders.

Prevalence and clinical significance of fever in acute exacerbations of chronic obstructive pulmonary disease.

Fever is an important, although not always present, sign in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The objective of this study was to determine the prevalence of fever and its clinical significance in these episodes. Two hundred seventeen AECOPD hospitalizations were included in a prospective study and were categorized as febrile (FH) or afebrile (AFH), using as a cutoff a rectal temperature measurement of 37.8 degrees C during hospitalization. Eighty-six hospitalizations (39.6%) were identified as AFH. The patients in this group had significantly more severe airway obstruction and hypoxemia, a higher rate of chronic obstructive pulmonary disease (COPD) complications, a higher rate of type 3 exacerbation, a shorter length of hospitalization and a higher rate of readmissions than patients in the FH group. The results of this study show that more than one-third of AECOPD hospitalizations are attributable to afebrile episodes. These episodes are characterized by lower rates of bronchitis manifestations in patients with more severe disease. Although the length of hospitalization for these episodes is shorter, the readmission rate is higher.