Model: dontia/embeddinggemma-300m-medical-Q4_K_M-GGUF
Author: dontia
Pipeline: sentence-similarity
Library: sentence-transformers
Tags: sentence-transformers, gguf, sentence-similarity, feature-extraction, dense, text-embeddings-inference, generated_from_trainer, dataset_size:100000, loss:CachedMultipleNegativesRankingLoss, llama-cpp, gguf-my-repo, en, dataset:tomaarsen/miriad-4.4M-split, base_model:sentence-transformers/embeddinggemma-300m-medical, base_model:quantized:sentence-transformers/embeddinggemma-300m-medical, license:apache-2.0, model-index, endpoints_compatible, region:us
Base models (quantized): id: sentence-transformers/embeddinggemma-300m-medical
Card metadata: language: en
license: apache-2.0
tags: sentence-transformers, sentence-similarity, feature-extraction, dense, text-embeddings-inference, generated_from_trainer, dataset_size:100000, loss:CachedMultipleNegativesRankingLoss, llama-cpp, gguf-my-repo
base_model: sentence-transformers/embeddinggemma-300m-medical
widget: source_sentence: What are the potential effects of stopping inhaled corticosteroid (ICS) therapy in patients with chronic obstructive pulmonary disease (COPD)?

sentences: Postoperative infections convey substantially increased clinical risks and increases in health care costs. Infections by Staphylococcus aureus (S. aureus), other gram positive organisms, including Clostridium difficile, gram-negative organisms including pseudomonas, Escherichia. coli, enterococci, and fungal infections are important because of their increasing frequencies, resistance to antibiotics, and associated deaths and disability [1] . Infections due to S. aureus are of particular concern in the face of increasing methicillin resistance (MRSA). A retrospective study of surgical patients based on medical records found 0.47 invasive S. aureus infections per 100 procedures, of which 51% were due to MRSA [2] . In that study, cardiothoracic procedures had the highest infection rate (0.79 per 100), followed by 0.62 per 100 for neurosurgical procedures, and 0.37 per 100 for orthopedic procedures. Among 133,450 S. aureus infections isolated from 1998 to 2009 from medical and surgical patients in an integrated health plan, 40% were MRSA [3] .

 Efforts to reduce the frequency of S. aureus infections following surgical procedures have focused both on prevention and treatment. Preventive measures aim to reduce nosocomial infections transmitted to patients by hospital workers or hospital facilities [4, 5] or on identifying and treating surgical patients who are carriers of MRSA organisms when they enter the hospital [4, 6, 7, 8, 9] . Use of the multicomponent MRSA bundle (nasal screening, contact isolation, hand hygiene, leadership, and monitoring) has been very effective in reducing the frequency of postoperative infections [10] . We focused our study on cardiovascular, orthopedic and gastro-intestinal surgery due to a combination of their high frequency in Medicare beneficiaries and the risks of were 15.0% infection in the literature.

 Infections related to cardiothoracic surgery are mainly wound infections, septicemia, endocarditis, and pneumonia [11] . Patients who have surgery on the ascending aorta and require 48 hours or more mechanical ventilation following the procedure or require reoperation and heart transplant recipients are at especially high risk [12] . Among orthopedic surgery procedures, knee or hip replacement or arthroplasty are accompanied by especially high risks of post-operative infections, with S. aureus being the most frequent organism cultured [13, 14] . A large questionnaire study found that infections following orthopedic surgery are usually not detected until after discharge from the surgical admission, often at a subsequent hospital admission [15] .

 To our knowledge, previous studies of postoperative infections caused by S. aureus, based on medical records, were limited to clinical populations in a few institutions and a few weeks of follow up. Our study uses claims data for a large and nationally representative sample of Medicare beneficiaries. To avoid missing delayed effects, we examine the occurrence of S. aureus infections for up to 180 days following common cardiovascular (CV), orthopedic, or gastrointestinal (GI) surgical procedures among Medicare beneficiaries. We also examine the effects of S. aureus infection on length of stay and mortality.

 

 The study was approved by the Brandeis University Committee for the Protection of Human Studies in Research. As the study was based entirely on existing data without patient names or identifying numbers, no patient consent was required.

 This study used Medicare entitlement data and Part A claims data (primarily inpatient hospital care) from the random 5% sample of beneficiaries in Medicare's chronic condition warehouse (CCW). The claims for such persons in the CCW as of Jan. 1, 2004 plus new entrants to the CCW through 2007 were pooled to construct the study's analytical file [16] .

 Three main categories of surgery were studied: CV, orthopedic and GI surgeries. CV surgeries were classified into coronary artery bypass graft (CABG), percutaneous coronary interventions (PCI), and other. PCI was included because it is the most frequent cardiovascular procedure, was usually done as an inpatient procedure in Medicare beneficiaries, and is often an alternative to CABG [17] . Orthopedic surgeries were grouped into hip, knee, or other. GI surgeries were classified into gastric, laparotomy, or other. Surgical procedures were identified by specific International Classification of Diseases (ICD) inpatient procedure codes listed in Table S1 . Codes were selected based on review of coding manuals, prior literature, and the medical knowledge of the two physician authors (WS, JS).

 The design was a retrospective cohort study consisting of Medicare fee-for-service patients in the 5% sample who underwent one or more of the specified types of surgery during an acute hospital admission., Stopping ICS therapy at 6 months leads to relapse of bronchial inflammation and hyperresponsiveness, dyspnea, and poorer health status, with acceleration of FEV 1 decline. Combination therapy with ICS and a long-acting ␤ 2 -agonist does not provide further anti-inflammatory effects compared with fluticasone alone but improves the level of Adjusted mean change in log-transformed bronchial cell counts (per 10 Ϫ7 m 2 lamina propria) over time during treatment with fluticasone, 500 g twice daily, for 30 months; fluticasone, 500 g twice daily, for 6 months plus placebo for 24 months; fluticasone, 500 g twice daily, and salmeterol, 50 g twice daily, for 30 months; and placebo, twice daily, for 30 months in patients with chronic obstructive pulmonary disease. Error bars represent 95% CIs. FEV 1 without further influencing FEV 1 decline. Our findings indicate that a subphenotype of patients with COPD who are steroid-naive and have moderate airway obstruction and airway hyperresponsiveness are sensitive to longterm ICS therapy. These prolonged effects on inflammation and lung function do not imply causality but suggest that disease modification can be achieved in particular phenotypes of patients with COPD.

 We observed differential effects of ICS on inflammatory cell counts. Although smoking may reduce corticosteroid responsiveness (31) , our data show that at least part of the inflammation in COPD remains sensitive to this treatment. The contribution of CD8 ϩ cells to inflammation and the relevant antigen-specific triggers in COPD are still unknown. CD4 ϩ cells may contribute to activation and memory formation of CD8 ϩ cells, as well as provide help for B cells (32). Mast cells and their secreted enzymes can drive various processes relevant to inflammation and remodeling (33) . Although in vitro studies suggest that corticosteroids are less effective in inhibiting activation of mast cells than activation of T cells (34) , our data indicate that corticosteroids can have selective anti-inflammatory effects in COPD. The observed increase in intact epithelium by ICS has also been found in persons with asthma (35) . Corticosteroid-induced changes in epithelial integrity and inflammation correlated with improvements in methacholine PC 20 , which supports the notion that airway hyperresponsiveness in COPD can be a marker of disease activity (36, 37) .

 The clinical novelty of our findings is that antiinflammatory effects observed with long-term ICS treatment associate with reduced FEV 1 decline in COPD. Previous short-term studies that investigated patients with COPD and similar degrees of airway obstruction (20, 21, 38) have shown anti-inflammatory effects of ICS in COPD. We show that these beneficial effects are maintained during long-term treatment of up to 30 months. The detrimental effects of discontinuing ICS therapy on Adjusted mean change and 95% CI over time during treatment with fluticasone, 500 g twice daily, for 30 months; fluticasone, 500 g twice daily, for 6 months followed by placebo for 24 months; fluticasone, 500 g twice daily, and salmeterol, 50 g twice daily, for 30 months; and placebo, twice daily, bronchial inflammation are also novel. Previous short-term studies of the combination of a LABA and ICS demonstrated anti-inflammatory effects versus placebo (39) or additional reductions of bronchial CD8 ϩ cells and macrophages versus ICS alone (22). Our data suggest that this is not a long-lasting additional effect; we observed a slight increase in CD3

 ϩ and plasma cells. The attenuated FEV 1 decline in our patients with COPD contrasts with large COPD trials from the 1990s (7) (8) (9) . The more recent TORCH study (15) did show reductions in FEV 1 decline in patients with COPD who received therapy with ICSs, LABAs, or both. Our results suggest that the improvement in the level of FEV 1 in the combination group might be due to a residual bronchodilator effect of salmeterol and not further disease modification. Discrepancies between the previous trials and our study may be due to differences in study samples, which may provide a clinical message.

 Our study comprised a common subset of patients with COPD. First, by choosing steroid-naive patients, we aimed to exclude patients with unknown previous benefits from ICS therapy at baseline and avoid the problem of selective dropouts in the placebo group., The messages that did not achieve significant improvements in knowledge postintervention ('Respect others' and 'Avoid drugs, alcohol and tobacco') did, however, record the two highest scores at the preintervention stage, which demonstrates the existing high level of children's knowledge in these areas. These two messages, which were retained from the original 'FIFA 11 for Health' programme, have consistently shown significant postintervention increases in knowledge in Africa and Latin America. [8] [9] [10] [11] The relatively higher baseline score for the message 'Respect others' may reflect differences in the status of women in Denmark and the focus of the session for Europe (respect and help others, avoid bullying) compared to the status of women and the content of the 'Respect women and girls' session used in previous interventions. For example, the lifetime prevalence of physical and/or sexual violence against women reported for Denmark was 28%, whereas in Brazil it was 39%, and in the five African countries this varied from 43% (Namibia) to 60% (Tanzania). 21 For the message 'Avoid drugs, alcohol and tobacco', the situation appears to be far more complex and the reason for the intervention not achieving an increase in children's knowledge remains puzzling considering the role of alcohol, for example, in the national cultures. For example, in the five African countries, alcohol consumption (L/capita per year) ranges from 2.5 in Malawi to 10.8 in Namibia and 8.7% in Brazil; whereas in Denmark, alcohol consumption is higher at 11.4 L/capita per year. 22 Scores for the PedsQL questionnaire identified significant improvements in the social and school dimension of well-being for the intervention group, but not for the control group. These results give further support to previously reported benefits of physical activity. In particular, it has been reported that 9-to 11-year-old children who meet the recommended daily physical activity guidelines exhibit higher well-being scores for satisfaction, comfort, resilience, achievement, self-esteem and social acceptance than children who do not. 23 There are many intervention programmes designed to increase physical activity or health knowledge of children, but only few programmes that attempt to increase both and none that has evaluated a combined physical activity and health education programme. 24 25 The closest in concept to the modified 'FIFA 11 for Health' programme is the school-based two-stage 'Dutch Obesity Intervention in Teenagers' (DOiT) programme: stage-1 is aimed at raising awareness about dietary energy balance and stage-2 is aimed at improving children's food choices and level of physical activity. 26 This programme achieved significantly lower levels of body fat, lower consumption of sugary drinks, and lower screen-viewing times among children aged 12-14 years. 26 27 Given the social, environmental, educational and financial situation in Europe, communicable diseases generally do not threaten the population to the extent that these do in other regions of the world. In Europe, NCDs are the major health threat due to consumption of unhealthy, convenience foods, and limited time spent on physically challenging activities: a situation of particular concern among children. 28 The current recommendation for physical activity is 60 min of moderate to vigorous activity daily for children 5 ; however, evidence shows that large proportions of children in Europe do not achieve this. 1 It has long been recognised that being overweight during childhood is a risk factor for being overweight in adulthood; [29] [30] [31] therefore, it is essential to address the problem of being overweight at school age in order to reduce the threat from NCDs in later life. The children's positive views about the programme together with the observed increases in health knowledge, and the social and school dimensions of well-being indicate that the proposed modified 'FIFA 11 for Health' programme could support the WHO regional campaign against NCDs in Europe. 6 What are the findings? ▸ The 'FIFA 11 for Health' education programme has been modified for the European setting. ▸ The modified programme focuses on physical activity and health knowledge related to non-communicable diseases among school-aged children. ▸ The modified programme increased levels of knowledge about non-communicable diseases among 10-to 12-year-old Danish school children. ▸ Children's scores on the social dimension of well-being were enhanced following participation in the programme.

 How might it impact on clinical practice in the future?

 ▸ Children in Europe show a high prevalence of overweight and obesity. ▸ National Governments are seeking cost-effective initiatives to reduce the economic and health burden associated with overweight and obese children. ▸ The 'FIFA 11 for Health' programme for Europe can be easily assimilated into school curricula to provide children with effective health education and physical activity.

 questionnaires provided by Johan Wikman, Line Sandager, Ida Lundager, Stine Nylandsted Jensen, Andreas Møller and Mads Madsen (Copenhagen Centre for Team Sport and Health, University of Copenhagen). In addition, the authors would like to thank the 9 schools in Frederikssund, Roskilde, Frederiksberg and Copenhagen Municipalities and the 22 individual teachers who delivered the programme in their schools, without whose support the interventions would not have been possible. Last, but not the least, the authors would like to thank the children who participated in the study.

 Contributors CWF modified the FIFA 11 for Health programme for the European context, analysed the data, prepared the first draft of the paper, revised the manuscript and approved the final submission. CO modified the FIFA 11 for Health programme for the European context, implemented the intervention, analysed the data, revised the manuscript and approved the final submission. MNL implemented the intervention, revised the manuscript and approved the final submission. A-ME implemented the programme, provided statistical analysis of the data, revised the manuscript and approved the final submission. LO implemented the programme, revised the manuscript and approved the final submission. AJ and JD modified the FIFA 11 for Health programme for the European context, commented on the manuscript and approved the final submission. PK modified the FIFA 11 for Health programme for the European context, implemented the intervention, analysed the data, revised the manuscript and approved the final submission.

 Funding FIFA Medical Assessment and Research Centre.

 Competing interests J Dvorak is the FIFA Chief Medical Officer.

 Provenance and peer review Not commissioned; externally peer reviewed.

 Open Access This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/, source_sentence: What are some potential factors that can contribute to force variability during constant isometric contractions?

sentences: index Wnger Xexion) because of the experiment by Prodoehl and Vaillancourt (2009) . Their results were similar to ours despite the fact that they used higher force levels than our study (5 and 40% MVC) and diVerent eVectors (elbow Xexion and dorsiXexion). One potential diVerence between the and Newell (2006a, b) was the monitor size. We used a 27 in. display, whereas SosnoV and Newell used a 17 in. display. It is possible that the visual feedback could have temporarily gone oV the screen on a 17 in. display such that subjects received less information at higher gains. Hong and Newell (2008) examined this issue and showed that at high feedback gain levels the visual feedback can exceed the screen height when the display is small (Hong and Newell 2008) . Nonetheless, all these studies agree that increases in visual feedback gain from low (e.g., 2 pixels/N) to moderate visual feedback gains (e.g., 64 pixels/N) will signiWcantly reduce force variability.

 The results of this paper also support recent Wndings (Baweja et al. 2009b) , which demonstrated that force variability did not vary signiWcantly when comparing 12.8 with 51.2 pixels/N and 15 with 3,000 pixels/N. In this paper, we examined 13 visual feedback gains per subject, and show that signiWcant diVerences in force variability reliably occur only when the comparison is between very low (0.5-4 pixels/N) and moderate-to-high visual feedback gains (>64 pixels/N). An interesting Wnding from the Baweja et al. (2009a, b) paper was that force variability was signiWcantly lower when visual feedback of the force was removed. Therefore, this could have indicated that at very low visual gains (close to 0 pixels/N) force variability would decrease. The current manuscript clearly demonstrates that even with extremely low visual feedback gains (0.5 pixels/N) force variability is signiWcantly higher compared with moderate visual feedback gains. It is possible that complete removal of visual feedback changes the strategies used by the subject to maintain the force constant. For example, the subject may rely more on proprioceptive information rather than searching for visual feedback to perform visuomotor corrections.

 It is well accepted that the variability in force during constant isometric contractions is primarily due to oscillations in force from 0-2 Hz Christou et al. 2004; Christou 2005; Baweja et al. 2009b ). Our Wndings clearly demonstrate that when the visual feedback gain increased from low to moderate visual feedback gains force variability decreased due to decreased power in the 0-1 and 3-7 Hz bands. The reduction in power from 0-1 Hz explained »50% of the decrease in force variability, whereas the reduction in power from 3-7 Hz explained »20% of the decrease in force variability. These results, therefore, demonstrate that visuomotor corrections can alter the oscillations in force via modulation of the 0-1 Hz and 3-7 Hz bands. Although other studies have shown that visuomotor corrections can change the oscillations in force (Miall et al. 1993; Baweja et al. 2009b ), these results demonstrate that low-frequency oscillations in force (0-1 Hz) cannot be entirely explained from visuomotor corrections. This is evident because force output at very low visual feedback gains (e.g., 0.5 Hz) also contained low-frequency oscillations (0-1 Hz). Low-frequency oscillations have been attributed to the coherent modulation of motor unit discharge at low frequencies (De Luca and Erim 1994; Brown 2000; Vaillancourt et al. 2003) , variability in motor unit discharge due to synaptic noise Moritz et al. 2005) , intrinsic neuronal properties such as active calcium conductance (Falcke 2003) , heart rate (Hunter et al. 2007) , and breathing (Turner 2002; Li and Yasuda 2007) .

 Furthermore, the exact physiological mechanism that induced the modulation (decrease in power) within these frequency bands remains unclear. One possibility is that the change in low-frequency oscillations (0-1 Hz) occurred by changing the breathing amplitude (Fulks et al. 2008) . The 3-7 Hz modulation can be potentially explained by decreasing the number of newly recruited motor units (initial rates of newly recruited motor units range from 5-7 Hz and contribute the most to the variability of force; Enoka and Fuglevand 2001) ., Cancer continues to be one of the leading causes of death both worldwide and in the United States. While incidence and mortality rates are both dropping in the United States, primarily attributed to reductions in smoking, the burden of the disease remains extremely high. The American Cancer Society estimates that 1,685,210 new cases were diagnosed in 2016 alone, and 595,690 patients succumbed to the illness [1] .

 Several natural and artificial substances have been found to be carcinogenic in humans. Benzene, a colorless liquid compound historically used in the printing industry as a component of inks as well as being a starting material in the chemical and drug industries (as a component in rubbers, lubricants, dyes, detergents, and pesticides) has been implicated in the causation of several types of leukemia and other blood-related cancers [2] . Since being identified as a human carcinogen, non-industrial use of benzene has been limited. However, industrial processes continue to release large amounts of benzene into the atmosphere, creating potential exposures for workers and the public at large.

 In recent years, researchers have begun using newer techniques to estimate the effect that exposure to ambient air pollutants, including benzene, has on the health of the general population. Mirzahosseini & Atabi [3] conducted a GIS-based study estimating the environmental benzene levels in Tehran, Iran. The methodology that the authors used was based on collecting samples at several locations around the city using a portable air monitoring device, and using those values to estimate ambient benzene levels around the city using the inverse weighted distance (IWD) technique. The authors found that the ambient levels of benzene in Tehran's air were between 2 and 20 times higher than the international standard (1.56 ppb). They also estimated the excess cancer risk imposed by the heightened benzene levels in different neighborhoods in Tehran using an excess risk model developed by the EPA. The study falls short, however, in investigating the association between benzene levels and observed cancer incidence or mortality, due to the unavailability of cancer outcomes data containing geographical markers.

 Eiten et al. [4] performed a spatial analysis of air pollution and cancer incidence rates in the Haifa Bay region in Israel. The exposures of interest in this study were PM 10 , resulting from vehicle traffic and industrial processes, as well as SO 2 , a marker of industrial emissions, while the outcomes of interest were lung cancer, bladder cancer, and non-Hodgkin's lymphoma. Using data from Israel's national cancer registry, the authors analyzed 143 residential wards (neighborhoods) in Haifa Bay and initially demonstrated that cancers did not follow a spatially random distribution. Subsequently, they used kriging to extrapolate region-wide estimates of the study exposures based on values from 17 SO 2 monitoring stations and 8 PM 10 monitoring stations within the study area. For each ward being analyzed, the average of the kriged estimates was used as the exposure level for the individuals who resided in each ward. The authors reported that SO 2 was not associated with any of the three types of cancer, but PM 10 showed a significant association with lung cancer in males, with each additional microgram in the environment associated with a 12% increase in lung cancer risk.

 The use of conventional linear regression models, such as Ordinary Least Squares (OLS) linear regression, presents the same problem of spatially autocorrelated residuals, violating the key assumption of independent and identically distributed error structure and alternative methods of testing the significance of any risk factors are necessary [5] . Statisticians have developed spatial regression models that are analogous to those models previously used for time-series analysis, which allowed for the correlation (in this case, between neighboring regions rather than subsequent time periods) in the outcome data [6] . This approach, which includes both simultaneous and conditional auto-regression models, allows modelling the observed values as the realizations of a distribution that depends on the values seen in neighboring areas [6] .

 Finally, the problem of using observed values to extrapolate over larger areas has been addressed using a method called kriging, introduced by Georges Matheron, who is considered the founder of geostatistical theory [5] . Kriging is a minimum-mean-squared-error used to predict spatial values based on the distribution of the observed values [6] . Various types of kriging have been developed, including simple kriging (analogous to linear prediction), ordinary kriging (based on a hypothetical mean that is common across the study region), universal kriging (where the mean structure is non-stationary, i.e., varying based on location) and block kriging (used to predict lattice data from geospatial observations)., Foreign body aspiration in toddlers, which presents a serious issue in developing countries, not only remains a diagnostic and therapeutic conundrum to otolaryngologists, but presents a major hazard to anesthetists, especially during emergencies when confronting the postoperatively compromised airway. Reports have focused on the ventilation mode and anesthesiology delivery route. The most suitable anesthetic technique for adequate ventilation and oxygenation during rigid bronchoscopy (RB) is still under investigation. The aim of this study is to review our 20-year experience (1991) (1992) (1993) (1994) (1995) (1996) (1997) (1998) (1999) (2000) (2001) (2002) (2003) (2004) (2005) (2006) (2007) (2008) (2009) (2010) in the airway management and the subsequent outcomes of RB in children with an inhaled tracheobronchial foreign body (TFB).

 

 

 Institutional review board approval from the Eye and ENT (EENT) Hospital of Fudan University (Shanghai, China) was obtained; a total of 3203 charts of children (<12 years of age) with suspected inhaled foreign bodies underwent RB in 1991-2010 (past 2 decades) were reviewed. Exclusion criteria included incomplete data sets (34 cases) and an emergency invasive airway (tracheal intubation or tracheostomy) prior to the RB procedure (20 cases); therefore, a total of 3149 patients were retrospectively studied. Data included patient characteristics (age, gender, weight, respiratory system impairment), foreign body details (type, duration, location), whether anesthetic management or complications ever occurred, and interventions and outcomes. An active respiratory symptom was referred to the presence of abnormal clinical signs or laboratory examination as follows:

 Wheezing symptoms with asthma history and/or pneumonia, atelectasis, or bronchiectasis diagnosed by a chest X-ray. The fl ow chart of the diagnostic algorithm of TFB aspiration in children at the EENT Hospital is shown in Figure 1 .

 Postoperatively pulmonary complications were defi ned as the existence of severe hypoxemia, laryngeal edema, complete laryngospasm, pneumothorax, atelectasis, and death.

 Anesthesia was induced by inhalational or intravenous anesthetics. The former was performed by 8% sevofl urane in oxygen (6-8 L/min) aspiration, while the latter was accomplished by the infusion of fentanyl 1 μg/kg and propofol 2.5 mg/kg. Ventilation modes during anesthesia maintenance were divided into two types: (i) Controlled ventilation (CV), in which small bolus doses of succinylcholine 1 mg/kg were repeatedly administered to maintain muscle relaxation and total intravenous anesthesia (TIVA) with propofol (150-250 μg·kg

 ) and remifentanil (0.1-0.2 μg·kg −1 ·min −1 ) infusion were used; and (ii ) spontaneous ventilation (SV), in which inhalation or intravenous drugs were administered. The former was delivered using the sevoflurane approach (8% in oxygen inhalation) with a semi-circle anesthesia breathing circuit, whereas the latter was delivered by the intravenous induction of γ-hydroxybutyrate (50-80 μg/kg) [1] or dexmedetomidine (1-2 μg/kg) over 10 min followed by an infusion of 0.2-0.6 μg·kg

 . Prior to RB insertion, 2% lidocaine (dose max 4 mg/kg) was sprayed onto the epiglottis and larynx and between the vocal cords.

 The choice of ventilation airway device was based on the anesthesiologist's experience and patients' circumstances. In patients with suspected subglottic TFB, an SV technique was used to avoid converting a proximal partial obstruction to a complete obstruction. The avoidance of positive ventilation was also used in cases of a defi nite preoperative mediastinum emphysema/pneumothorax for fear of inducing iatrogenic-related barotrauma. CV and SV are the two main techniques used during RB. CV is composed of intermittent positive pressure ventilation (IPPV) and manual jet ventilation (MJV). In the IPPV group, PPV was commenced through the breathing circuit, which was connected as a T-shaped piece to the side arm of the RB (Storz, Tuttlingen, Germany)., source_sentence: What are the key features and etiologies of giant cell interstitial pneumonia (GIP), and how does it manifest in viral infections and pneumoconiosis?
sentences: The calcium ion (Ca 2+ ) is very important in the regulation of several signaling pathways that are contributed to many cellular processes such as proliferation, differentiation, apoptosis, gene expression, and fluid and hormones secretions. The (Ca 2+ ) homeostasis is monitored under the effect of certain G-protein coupled receptor-family C known as calcium sensing receptor (CASR). 2 The highest expression of CASR is usually seen in the kidney and the chief cells in parathyroid tissues. However, other organs may express CASR on their surfaces such as colon. 3 In the colon, CASR enhances the differentiation of colonocytes which in turn reduces the formation of neoplasia in the colon. 4 Moreover, it inhibits fluid and electrolyte secretion, which could potentially serve as a treatment for diarrheal disease. 5 It may also help the ions of Ca 2+ to upregulate proteins which modulate duodenal Ca 2+ absorption in vivo, although the certain molecular mechanisms behind this physiological process are not clear. 6 The human CASR gene is located on chromosome 3q13.33-q21.1 and contains 11 exons, two promoters and two 5′-untranslated exons (exon 1A and 1B) that yield alternative transcripts, but encoding the same protein. 7 As many other genes, any genetic variations in the CASR gene, either in the form of mutations or single nucleotide polymorphisms (SNPs), can result in a loss or gain of function, which in turn lead to significant alterations in circulating concentrations of calcium that is associated not only with disorders of the parathyroid glands, but also with other conditions such as bone disorders, vascular disorders, and cancer.

 Colorectal cancer (CRC) is considered one of the most prevalent cancers with high incidence and morbidity rate worldwide. According to the latest report from the National Cancer Registry (NCR) at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Saudi Arabia, CRC represents the first and the third most common cancer types among males and females, respectively.

 8 Although significant advances in the diagnosis and treatment have been made for CRC patients in Saudi Arabia, the overall 5-year survival rate was (44.6%) for the period 1994-2004 with a high percentage of distant metastasis (28.4%) in patients at the time of presentation and rectal cancer represented (41%) of all colorectal cancer cases diagnosed in 2010. 8 This poor overall 5-year survival rate is partially due to the lifestyle such as diet and physical activity and partially due to acquired drug resistance. The CASR is able to respond to a variety of ligands, including polyvalent cations and amino acids. Therefore, any changes of pH and ionic strength that occur in cancer cells may affect the activity of the CASR and subsequently affect its capability to integrate several signaling pathways. Most of the published articles revealed that CASR expression play a protective role in CRC patients through several mechanisms such as binding toxic secondary bile acids and/or ionized fatty acids and neutralizing them in form of insoluble calcium soaps, 10 or by affecting several signaling transductions such as stimulating cell differentiation, inducing apoptosis and inhibiting proliferation.

 11 To the best of our knowledge, no studies have been conducted to correlate the relation between genetic polymorphisms in CASR gene and risk of CRC in Saudi patients. Therefore, this study was aimed to determine the genetic distribution and allele frequency of two SNPs in CASR gene in drug-resistant CRC patients that are routinely visiting King Abdulaziz University Hospital (KAUH) to reveal the possible effect, if present, on the pathogenesis of CRC.

 In this study, 100 CRC patients and 124 controls were included. The purpose of the research was explained and a written consent of the participants as well as their answers on a questionnaire were obtained. The study was approved by the biomedical ethics unit at faculty of medicine, King Abdulaziz University (KAU) (reference no. 378-17). Several anthropometric measurements such as body weight, height, body mass index (BMI), waist and hip circumference, and waist-to hip-ratio (WHR) were calculated for all participants. All blood samples were drawn into lavender top vacutainers containing anticoagulants (EDTA) and were obtained from oncology clinics at King Abdulaziz University Hospital (KAUH) in Jeddah, KSA from the period January 2016 to September 2016. Genomic deoxyribonucleic acid (gDNA) was extracted from peripheral blood leukocytes in whole blood samples using QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany) following the manufacturer's instructions., Katzenstein, but in addition, also cases showing fibroblastic foci associated with emphysema blebs and fibrosis (Fig. 20) . In these cases, also RB could be seen in different areas. In contrast to UIP, there were no honeycomb lesions and almost all lobules showed changes of centrilobular emphysema. Some of these patients were clinically diagnosed as having chronic obstructive pulmonary disease (COPD); in others, the lesions were found incidentally because of pneumothorax. So this might represent another form of smoking-induced lung fibrosis, probably resulting from the release of toxic enzymes from macrophages and subsequent alveolar septa destruction and repair.

 Acute interstitial pneumonia/diffuse alveolar damage Many different agents can cause AIP/DAD. Classical ones are viral infections, but toxic inhalation, drug reactions, and all variants of shock reactions will also present with this morphologic picture. The features have been described above, so we need to focus only on specific changes pointing to a specific etiology. In viral infection, the most characteristic feature is the viral inclusion body, which can present either as nice large inclusion bodies (cytomegalovirus [CMV], respiratory syncytial virus [RSV]) or by red-violet-stained nucleic acids forming illdefined speckles in nuclei and/or cytoplasm (adenovirus) [27] . Typically, the infected cell shows enlargement, an atypical large bizarre nucleus, and an accentuated nuclear membrane due to increased nucleic acid traffic induced by the virus. These cellular features can last for several months. In contrast to preneoplastic lesions in viral infection, the atypical cells are single cells being grouped together with otherwise normal-looking pneumocytes.

 Giant cell interstitial pneumonia (see also under pneumoconiosis) GIP has a quite narrow etiologic spectrum either being caused by hard metal dust or by viral infection. The former will be discussed later. Several viruses can cause GIP, the classical one being measles virus. However, in contrast to pneumoconiosis in infections, the giant cells are mixed epithelial as well as macrophagocytic. The epithelial giant cells (Hecht cells) are transformed pneumocytes type II in whom nuclear division was not followed by cell division, giving rise to multinucleation [110] . The additional features are identical to DAD as described above. Especially within the epithelial cells, viral inclusion bodies can be found (Suppl. Fig. 36 ). Besides measles, RSV can also present, with this picture predominantly in children [111] .

 We have already described OP under the idiopathic ILDs, so we have only to focus on other causes of OP. OP can have a great variety of causes. In many cases, this is a post-infectious organization of a purulent bacterial bronchopneumonia, when for several reasons the exudate could not be completely degraded and, therefore, has to be organized by granulation tissue. Also, in viral infections, organizing DAD is morphologically identical to OP, as discussed previously. In other cases, OP is a form of organization of an autoimmune disease, usually in the inactive phase. The resolution phase of toxic inhalation is usually in the form of OP, and drug-induced lung toxicity is also often organized the same way (Suppl. Fig. 29 ).

 Chronic pneumonia of infancy Originally, surfactant-related IP with alveolar proteinosis were included into chronic pneumonia of infancy (CPI); however, since the different causes of alveolar proteinosis were discovered, it has been excluded. Therefore, CPI has been reduced to those pediatric interstitial diseases with unknown cause. It is now quite rare. CPI is characterized by an infiltration of lymphocytes and macrophages/histiocytes in the alveolar septa, accumulation of debris within the alveoli, and hyperplasia of type II pneumocytes (Suppl. Fig. 37 ), all causing thickening of the septa and impaired gas exchange. CPI predominantly occurs in newborn or small children [112, 113] . In many instances, a careful investigation of the biopsies might uncover underlying infectious diseases, such as Wilson-Mikity syndrome and infections caused by respirotropic viruses, Chlamydiae, or uroplasms [114] ; another cause might be gastroesophageal reflux [115] . In rare instances, a metabolic disease, interstitial glycogenosis, might be the cause of CPI [116, 117] ., The consequences of pulp exposure from caries, trauma or tooth preparation misadventure can be severe, with pain and infection the result. The morbidity associated with treating pulp exposures is consequential, often requiring either extraction or root canal therapy. Both the loss of the tooth and its replacement, or endodontic treatment and tooth restoration, involve multiple appointments and considerable expense. An alternative procedure to extraction or endodontic therapy is pulp capping, in which a medicament is placed directly over the exposed pulp (direct pulp cap), or a cavity liner or sealer is placed over residual caries (indirect pulp cap) in an attempt to maintain pulp vitality and avoid the more extensive treatment dictated by extraction or endodontic therapy. Although many products have been suggested, a recent Cochrane Review found that evidence is lacking as to the most appropriate pulp capping material. 1 In addition, various factors are believed to influence the success of both direct and indirect pulp capping. It is the purpose of this literature review to examine the evidence, issues and materials relevant to pulp capping.

 This review was undertaken as preparatory work for an essay at the annual meeting of the Academy of Operative Dentistry. It also served to provide the background and scientific rationale for a clinical trial on direct pulp capping being undertaken in the Northwest PRECEDENT Practice-based Research Network (PBRN).

 No specific criteria were applied a priori as to what articles would be accepted into this review. Rather, it was hoped that the span of literature reviewed would be as comprehensive as possible. PubMed and Ovid databases were searched for any articles that met the criteria of containing "pulp capping," "direct pulp capping," "indirect pulp capping," "sealed dental caries" or "pulp capping materials." No date limits were applied. An initial screen of returned abstracts was accomplished, and relevant full-length articles from peer-reviewed periodicals were obtained. Pertinent citations contained in the full-length articles were used as sources for additional review.

 The ultimate goal of a review such as this is to derive conclusions based on the evidence that can be applied to clinical practice. Just as any astute clinician will discuss the procedures, advantages, risks and patient questions (PARQ) prior to initiating a course of treatment, it is important for the reader to be aware of the shortcomings in the greater body of literature regarding pulp capping. It is only in this context that the reader can be aware of the challenges and shortcomings inherent in drawing definitive conclusions from the pulp capping literature. The following "informed consent statements" are for the purpose of stressing these challenges and shortcomings.

 The typical clinical study for pulp capping contains the following features:

 1. The patient is young (typically 15-25 years of age) and healthy.

 2. The patient is going to have premolars (subject teeth) extracted for orthodontic reasons.

 3. The subject teeth are free of caries, cracks or other defects.

 4. The teeth are isolated with a rubber dam, receive a pumice prophylaxis and are often times disinfected (sometimes with two antibiotic solutions).

 A sterile bur is used to initiate cavity preparation. When nearing the pulp, a new sterile bur is replaced in the handpiece and pulp exposure is initiated as atraumatically as possible.

 6. Hemorrhaging is controlled with sterile materials.

 While these procedures help to standardize the experimental technique and maintain internal validity, they do not reflect the circumstances under which most practitioners are confronted with a potential pulp cap situation.

 The true "gold standard" of pulp status is histological analysis. Unfortunately, the true state of pulp health or pathology cannot be determined by clinical signs, symptoms or radiologic appearance. Clinicians have only relatively crude assessments, such as the application of hot or cold temperatures, an electric current, percussion of the tooth, changes in the appearance of associated soft tissues and patient reports of symptoms. However, numerous studies including histological analysis have demonstrated a chronically inflamed pulp, but the patients reported no symptoms, the investigators discerned no signs and no apical/radicular pathology was noted on radiographs. It must also be kept in mind that most studies that include histological analysis are of quite a short duration, typically two to four months.

 3-4,6-9

 Much research on pulp capping has been accomplished in animals, from lower species, such as mice and dogs, to primates. However, the results of pulp capping in animals often does not reflect what will happen in humans. It is necessary to be very cautious in taking the results of animal pulp capping studies and applying them to human patients.

 3-4,7,10-12

 Some studies do not maintain a consistent methodology within the study. For example, the restorative regimen may vary among the experimental groups., source_sentence: How does serum P2-microglobulin (32-m) level relate to renal impairment in multiple myelomatosis?

sentences: SEVERAL INDICES have been proposed for the clinical stratification of multiple myelomatosis. The system devised by Durie & Salmon (1975) , using a panel of clinical biochemical factors, has the advantage of being correlated with survival and predictive of the response to treatment. Hence any new biochemical test, to be considered seriously for the stratification of multiple myelomatosis, must be capable of providing information comparable to the more complex systems in current use. There is growing evidence that serum P2-microglobulin (32-m) level is often increased in multiple myelomatosis (Shuster et al., 1976; Belleville et al., 1978) . However, P2-m is a low-mol. wt. protein (11,800 dalton) and its serum levels depend on both its production and its renal clearance. Elevation of serum /2-m occurs in renal clearance. Elevation of serum :2-m occurs in renal impairment (Revillard, 1979) . As some form of renal involvement will occur eventually in about half of the patients with multiple myelomatosis (DeFronzo et al., 1978) it could be argued that the measurement of serum /2-m is only providing refined information about multiple myeloma that might be of particular importance in patients with normal serum creatinine, and may be a simple substitute for the serial measurement of paraprotein levels in the monitoring of multiple myelomatosis.

 Two group of patients were studied; all fulfilled the accepted criteria for the diagnosis of myelomatosis (Chronic Leukaemia-Myeloma Task Force, 1973 Kaplan & Meier (1958) and the significance between the survival of the subsets calculated by the log-rank method (Peto et al., 1977 The serum /2-mn was measured by the Phadebas radioimmunoassay (Pharmacia, Uppsala, Sweden). The normal limits for this assay in blood donors are 0 8-2-4 mg/l. Creactive protein was measured by radial immunodiffusion, using antisera and standards obtained from the Behring Institut, Marburg/Lahn, Germany. Serum levels > 10 mg/l were considered abnormal, but a discriminant level of 20 mg/l was adopted as being indicative of active infection. Serum creatinine was measured by Jaffe's method: a value of 140 HM wNas arbitrarily taken as the upper limit of normal in this population. The choice of the serum /2-m 4 mg/l cut-off as the basis for stratification of the patients into good and bad prognosis groups wAas made after reference to results obtained in "normal" subjects, over 60 years of age, AN-here the median was 2-2 mg/l and range 1 2-40 mg/l (Agerup, personal communication) .

 The general relationship between serum /2-m level at first presentation and the probability of survival in Group I, is shown in Fig. 1 The relation of serum f2-m levels and creatinine levels in patients in whom renal impairment is indicated by elevated creatinine, is shown in Fig. 4 , where comparison is made with the regression slopes for these variates in chronic renal failure and systemic lupus erythematosus, as published by Hall (1979) . It will be seen that there is a wide range of serum ,82-m levels for a particular creatinine level. The correlation coefficient, as measured by the Spearman ranking test, was r = 0-61, P = 0.01. In the longitudinal studies, levels of serum ,B2-m > 15 mg/l were always associated with creatinine > 140 ,uM. But considerable change in serum ,82-m levels, either downwards during the reduction of the larger tumour burdens or upwards as the mass expanded, could occur without a coincidental change in serum creatinine.

 The discriminant power of serum ,B2-m level of 4 mg/l is apparent from the survival studies (Fig. 1) where good and bad prognostic groups are distinguished. It will require a larger series to define the level for optimal separation of these 2 groups. There is also a clear relation between serum /2-m levels and estimates Hall (1979) .

 of tumour mass, using the system devised by Durie & Salmon ( Once the creatinine begins to rise, the effect of hyperproduction is magnified and the serum /2-m is elevated more than is usual for chronic renal disease. Assuming that the raised levels are due to excess production, it is not known whether this P2-m comes from the mature plasma cells, their precursors or other cells of the lymphoid series. Studies of lymphoid disease indicate that raised serum /32-m can accompany a variety of benign and malignant diseases involving B or T lymphocytes (Cooper & Spati, 1979) . Whatever the cell type or types contributing to the production df /2-m, its origin is most probably from the turnover of HLA on cell membranes, where /2-m forms the light chain of HLA (Cresswell et at., 1974) .

 In practice the measurement of serum /32-m, at first presentation, would appear to be useful for the stratification of multiple myeloma, especially when the creatinine level is normal. The frequency of a renal impairment at first presentation has been reported as 43/237 (18-1%) by Woodruff et al. (1979) , and 18% by Alexanian et al. (1975) using criteria less strict than ours.

 High levels of serum P2-m at diagnosis or after 12-18 months carry a poor prognosis, and such levels are frequently encountered in IgA and IgG myeloma without an elevated serum creatinine (Table II) . Furthermore, serum /2-m could well be a better reflection of the tumour mass than the serum paraprotein levels, and may offer a particular advantage for the monitoring of Bence Jones myelomatosis, as it is difficult to measure the serum concentrations of light chains accurately. Severe acute infections do not necessarily raise serum 32-m, which is independent of the serum acute-phase reactive protein response (Cooper & Spati, 1979) . This may account for the lack of rise of P2-m in the terminal periods of life of those patients in Fig. 1 and 2 whose intercurrent infection was the immediate cause of death.

 Measurement of serum 32-m is simpler and less problematical than existing staging systems and paraprotein estimations. It may prove particularly applicable to the stratification and subsequent monitoring of patients with myelomatosis in the multi-centre clinical trial., The joint is multiply innervated such that anesthetics applied to the exiting dorsal sacral nerve roots blocks sensation outside the joint but not pain elicited by joint pressurization. 7 In blinded randomized trials, radiofrequency ablation (RFA) of sacral nerve root lateral branches was effective in at least temporarily relieving pain in patients with SIJ pain, 8, 9 providing definitive proof not only that the SIJ is a source of pain but also that the pain can be treated successfully.

 SIJ pathology can cause proximal buttocks pain that may radiate into the lower back, groin, or lower extremity. 6 In a detailed diagnostic study of outpatients with lower back pain, the SIJ was thought to be the source of up to 15-23% of all chronic lower back pain. 10, 11 SIJ pain is an even more common explanation for post-lumbar fusion lower back pain. 12 Causes of SIJ pain include osteoarthritic degeneration, SIJ disruption as a result of trauma or pregnancy, inflammatory disease, tumor, and infection. Radiographic findings in the SIJ are common 13 but are not necessarily predictive of the presence of SIJ pain. In typical practice, crosssectional imaging of the pelvis and lumbar spine is done to rule out other concomitant pathology that could explain pain in the buttocks or groin.

 Nonsurgical treatments for SIJ disorders include medical management, physical therapy, manipulation, intra-articular steroid injections, prolotherapy, chiropractic, and RFA. Other than for RFA, no high-quality evidence exists to support the effectiveness of nonsurgical treatments for SIJ pain. Two blinded controlled trials of RFA of sacral nerve root lateral branches have shown short-term improvement in pain 8, 9 ; a 12-month follow-up study showed a modest long-term response rate after this treatment.

 14 SIJ fusion was first described in the 1920s, 15 and several singlecenter retrospective reports suggest that it may be moderately effective for the treatment of pain in this patient population. [16] [17] [18] [19] [20] [21] Pain relief is likely mediated by SIJ stabilization, reducing the need for active coordinated muscular control and passive ligamentous stability to facilitate effective load transfer across the SIJ. Unfortunately, open SIJ fusion is highly invasive and is associated with long hospital stays and recovery times, high nonunion rates (9%-41% 18, 22, 23 ), poor long-term response rates, and low levels of satisfaction. 24 Minimally invasive SIJ fusion systems are now available using various US Food and Drug Administration-cleared implants. Placed through less invasive surgical approaches, these devices are designed to provide the benefits of SIJ fusion with faster recovery times as a result of reduced iatrogenic injury to surrounding tissues. Minimally invasive SIJ fusions now account for 90% of all SIJ fusions. 25 Most published reports (primarily single-center retrospective cohorts [26] [27] [28] [29] [30] [31] [32] and a combined multicenter analysis 33 ) describe the placement of multiple triangular titanium implants coated with a porous titanium plasma spray (iFuse Implant System, SI-BONE, Inc, San Jose, California) across the SIJ under fluoroscopic guidance. These reports provide evidence that minimally invasive SIJ fusion relieves pain and disability.

 Previously, we reported 6-month results of a randomized controlled trial comparing SIJ fusion using iFuse Implant System and nonsurgical management (NSM) . 34 This study showed that SIJ fusion produced superior improvements in pain, disability, and quality-of-life outcomes at 1, 3, and 6 months after treatment relative to NSM. This report presents the 12-month follow-up from this study, including an analysis of subjects who crossed over from NSM to surgical treatment after the 6-month visit (which was permitted according to the study protocol).

 Investigation of Sacroiliac Fusion Treatment (INSITE) is an ongoing prospective, multicenter, parallel-group, unblinded randomized controlled trial. Enrollment took place between January 2013 and May 2014 at 19 spine surgery clinics in the United States. The study protocol (registered on http://www.clinicaltrials.gov [NCT01681004]) was approved by the Institutional Review Board at each participating clinical site before patient enrollment. The study was sponsored by the device manufacturer (SI-BONE, Inc). All study sites underwent both remote and periodic on-site data monitoring and all study data were source verified.

 Adult (age, 21-70 years) patients were eligible to participate if they had a confirmed diagnosis of SIJ dysfunction caused by degenerative sacroiliitis or SIJ disruption., For example, some respondents described infertility treatment as a service that hospitals wanted to hold on to, even if they had to make creative arrangements for the aspects prohibited by Catholic doctrine. Catholicism teaches that procreation should not be separated from intercourse within the context of heterosexual marriage. Thus, procedures to extract eggs or sperm, or to fertilize an egg in vitro, are prohibited in a Catholic facility. But provision of fertility drugs is permitted, as are medical visits that do not involve handling eggs, sperm or embryos. Noting that no one at her Catholic facility was allowed to provide fertility services, one respondent explained:

 "Now, they're getting a little crafty with how they get around it, and they go off-campus [to provide such services]. So we actually do now have…an infertility specialist, who is starting up an in vitro fertilization clinic off-campus.… We had somewhere to send them anyway before-it was just out of the system-but now the system wants the business."

 Similarly, one perinatologist explained that her Catholic hospital objected when she suggested that she stop accepting obstetric patient transfers during the previable period because she could not provide a full range of care to those patients. This respondent had cared for a pregnant patient whose fetus had a severe heart defect, and the patient' s membranes had ruptured at 19 weeks. The respondent had approved an induction of labor, and had then been accused by her Catholic ethics committee of performing an illicit abortion. The respondent recounted her response and subsequent interaction with the ethics committee:

 " After the meeting, the respondent noted that once the opposition had left the room, "several people came up to me and said, 'No, no, no, don't stop accepting those patients. ' [The] nurse vice president, the chairman of the ethics committee, kind of quietly afterwards…[came] up to me and [said], 'You know, we don't disagree with what you did, and we don't want you to not accept those referrals…because we're a referral hospital, and you start losing community hospitals, where getting to another hospital for urgent treatment may be especially diffi cult.

 One of the strengths of this study was that it included a diverse group of obstetrician-gynecologists who have worked in Catholic hospitals around the United States. Our open-ended interviews allowed themes about referral processes and barriers to emerge naturally in the respondents' own words and from their personal experiences. Most of the physicians we interviewed were drawn from a nationally representative survey sample, but the interview sample itself was not representative, so we cannot generalize respondents' experiences and perspectives to the entire population of U.S. obstetrician-gynecologists.

 It is also important to note that the hospital policies described here are fi ltered through the experiences and perspectives of the physicians interviewed. We did not directly speak to hospital administrators, ethicists or others in position to enforce the Catholic directives. In the survey from which this sample was derived, 48% of obstetrician-gynecologists who described religion as "not very important" in their lives experienced a confl ict with their religious hospital, compared with 20% of those for whom religion was "most important."

 11 Physicians' own beliefs and attitudes may therefore affect their reporting of hospital referral policies.

 Little research has been done on referrals for reproductive health services. In a nationally representative survey, primary care physicians were asked what doctors should do when they felt a service was clinically indicated but was prohibited by their hospital' s religious policies. Some 86% responded that the right course of action was to refer the patient to a different facility. 15 But this belief may not readily translate into patients' getting timely information and referrals, and barriers other than Catholic hospital policy may also play a role. In a 2010-2011 study of reproductive health facilities (not specifi cally religious ones) that did not provide abortion but were located fairly near an abortion provider, callers posing as patients received a direct abortion referral in only 46% of instances. 16 In a separate study, in Nebraska, only 52% of family medicine providers and obstetrician-gynecologists believed that clinicians have a professional obligation to refer patients for abortion services, and 17% said they would in no way participate in an abortion referral. 17 The nonprofi t organization Provide reviewed both published literature and expert guidance on abortion referrals, and found a need for research evaluating the effectiveness of abortion referrals and the role of the referral process in women' s access to care. 18 Prominent bioethicists and obstetrician-gynecologists have debated whether physicians who hold a personal moral objection to abortion should be required to refer patients to a physician who will safely provide it. 19, 20 However, they have not addressed the behavior of institutions (or the not have the option of providing abortions for their own patients the way others would., source_sentence: What are some potential limitations in projecting the future demand for joint replacement surgeries?

sentences: The chronic inflammation of rheumatoid arthritis mainly affects the synovial membranes of multiple joints and potentially involves vasculitis and pulmonary, ocular and cardiovascular systems. After the onset of the inflammation, the synovium changes dramatically (Edwards, 1998) . The synovial intima is filled with B-lymphocytes engaged in antibody production against unknown antigens (Bläß, Engel, & Burmester, 1999) . Infiltrations of plasma cells into the synovia are highly associated with inflammation of rheumatoid arthritis (Dong, Li, Liu, & Zhu, 2009; Reparon-Schuijt et al., 1998) . The resulting immune complexes activate macrophages and complement and drive a T-cell dependent antibody production in the synovial tissue. The immune complexes are mainly rheumatoid factors that are defined as auto-antibodies against Fc-fragments of IgG (Tighe & Carson, 2001) and occur in about 90% of rheumatoid arthritis patients (Dörner, Egerer, Feist, & Burmester, 2004) . Normally

 Rheumatoid arthritis is a desastrous progressive autoimmune disease for which no causative cure is available, simply because the eliciting antigens are unknown despite intesive research efforts. Most patients have also Rheumatiod factor activity where antibodies bind to their own structures within the constant region. Here we considered, wether mutations in the constant regions of immunoglobulins could represent the eliciting antigens.

 rheumatoid factors bind to an antibody-antigen complex and facilitate clearance by binding to Fcreceptors, fixation of complement and antigen processing by B-lymphocytes (Carson, Chen, & Kipps, 1991) . The rheumatoid factor binding site resides in CH 2 -CH 3 domain of Fc (Artandi, Calame, Morrison, & Bonagura, 1992; Bonagura et al., 1998; Sutton et al., 1998) . However, rheumatoid factors are also found in other conditions of B-cell hyperreactivity.

 The driving force for autoimmune diseases are self-reactive antibodies directed against "altered self" which can be modified proteins (Trouw, Huizinga, & Toes, 2013) . So far posttranslational modifications have been detected in citrullinated antigens that are highly specific for rheumatoid arthritis. Citrulline residues arise from arginine by peptidyl arginine deiminase. However, this posttranslational modification cannot fully explain the pathogenesis of rheumatoid arthritis (Klareskog, Amara, & Malmström, 2014) .

 Changes of IgG glycosylation in the IgG were also thought to be involved in rheumatoid arthritis (Parekh et al., 1985) , but recent studies showed that the glycosylation loci are not associated with rheumatoid arthritis (Yarwood et al., 2016) .

 Other modifications include oxidized IgG that are recognized by circulating lymphocytes leading to a proliferative response and secrete IL-2 (Grinnell, Yoshida, & Jasin, 2005) . IgG is also covalently cross linked by reactive oxygen and nitric oxide products secreted by inflammatory cells (Uesugi, Hayashi, & Jasin, 1998) .

 IgG has long been implicated in the pathogenesis of rheumatoid arthritis. When immune complexes from synovial fluids of patients with rheumatoid arthritis were analyzed for their constituents, mainly IgG and IgM antibodies were found (Male & Roitt, 1981) . They did not contain antibodies with rheumatoid factor specificity and a structural alteration of the IgG was considered as a cause for antigenicity (Carter, Makh, Ponsford, & Elson, 1989) . Sutton, Corper, Bonagura, and Taussig (2000) suggested that rheumatoid factors bind Fc-region and foreign antigen antigens simultaneously and the affinity is potentiated by somatic mutation. Indeed, Fc-binding antibodies from rheumatoid arthritis synovial fluids show imprints of an antigen-dependent process of somatic hypermutation and clonal selection in the variable regions of the L-and H-chains (Van Esch et al., 2003) . It is clear that the synovium of patients with rheumatoid arthritis is prone to mutations (Firestein, 2010) and several multi-evidence genes in genome wide studies have been identified (Whitaker et al., 2015) ., 23 In cases of splenic B-cell lymphomas that do not fulfill the World Health Organization 2008 criteria for better established or provisional entities, a diagnosis of splenic B-cell lymphoma/leukemia unclassifiable should be preferred.

 Differentiating SMZL from lymphoplasmacytic lymphoma (LPL) may be challenging, particularly on BM biopsy, because SMZL may show a monoclonal serum component and plasmacytic morphology, and both entities lack a distinct phenotype. LPL, which develops primarily in the spleen, homogeneously infiltrates the white pulp without MZ pattern and without monocytoid B cells. MYD88 L265P mutation, present in almost all cases of LPL and rare in SMZL, may be a useful diagnostic tool. 25 A further diagnostic pitfall may be represented by detection of a BM clonal infiltrate in cases of non-CLL monoclonal B lymphocytosis. 26 Finally, secondary splenic localization of EMZL presents a pattern that overlaps with that of SMZL, but clinical dissemination is crucial for differentiation. Splenic involvement virtually excludes a diagnosis of nodal MZL; apart from the differential expression of IRTA1, which is negative in SMZL, 11, 22 clinical correlation is critical for reaching a correct diagnosis when dealing with a BM biopsy.

 The cellular origin of SMZL is still debated, and its identification is essential to correctly classify this lymphoma and to elucidate its pathobiology. According to the World Health Organization classification, the postulated normal counterpart of SMZL is a B cell of unknown differentiation stage. 11 According to studies of Ig gene rearrangements, a derivation from antigen-experienced B cells has been postulated in the 

 -, ,25% of cases; -/1, 25%-50% of cases; 1/-, 50%-75% of cases; 1, .75% of cases.

 FL, follicular lymphoma; NMZL, nodal marginal zone lymphoma; SDRPL, splenic diffuse red pulp lymphoma.

 *Sporadic cases reported.

 vast majority of SMZL. [27] [28] [29] Skewing of the Ig gene repertoire toward the use of the IGHV1-2*04 allele in SMZL suggests that they could derive from a progenitor population adapted in the spleen to particular antigenic challenges, although definitive answers on the issue of the cell of origin of SMZL will admittedly be provided only through multidisciplinary examination of the immune repertoire and transcriptome of normal B-cell populations of the spleen compartments.

 The contribution of antigen stimulation to SMZL pathogenesis is suggested by the highly restricted Ig gene repertoire, including stereotyped configuration of the B-cell receptor (BCR) in ;10% of cases 30 and selective usage of the Ig heavy chain variable IGHV1-2*04 allele in ;30%.

 31 Although the epitope recognized by IGHV1-2*04-expressing BCR is unknown, the features of IGHV1-2*04 rearrangements, including minimal somatic mutations and the long complementarity-determining region 3 sequence with common motifs, suggest a possible selection of T-cell-independent MZ B cells by superantigens and thus a role of antigenic drive in lymphomagenesis.

 Cytogenetic and genetic lesions SMZL lacks recurrent chromosomal translocations, including translocations that are typical of other lymphoma types such as the t(14;18) translocation affecting BCL2 in follicular lymphoma, the t(11;14) translocation affecting CCND1 in MCL, and the t(11;18), t(14;18), and t(1;14) translocations affecting the BIRC3/MALT1, MALT1, and BCL10 genes, respectively, in EMZL. The lack of these abnormalities may help distinguish SMZL from pathologically mimicking tumors. Approximately 30% of SMZL show hemizygous 7q deletion, which is also frequently seen in splenic B-cell lymphoma/leukemia unclassifiable, but rarely in other lymphoma subtypes.

 32,33 The gene(s) targeted by the 7q deletion remain obscure despite the combined investigation of genomic and transcriptomic profiles and mutation analysis of a number of candidate genes.

 Unbiased genomic studies have unraveled the typical coding genome of SMZL. [37] [38] [39] [40] [41] [42] [43] However, because of the limited number of SMZL genomes and/or exomes available so far, the full spectrum of lesions that contribute to the malignant transformation of SMZL remains unknown., We also asked whether current trends are advancing according to earlier expectations [6] .

 Our study has several limitations. Our projections are based on the historical growth trajectory of joint replacement surgeries, and do not take into account potential limitations in the availability of surgeons or limited economic resources by private and public payers and hospitals in the future. For example, a shortage in the number of surgeons will have a substantial influence on the actual number of procedures that are performed. We also have not incorporated the potential for future alternative technologies, such as cartilage regeneration or tissue engineering, or drug therapies that limit the progression of joint diseases, which may preempt the need for TJR. We were also unable to account for the potential impact of changes in economy, which may place additional economic burden on patients to pay substantial out-of pocket expenses for these procedures, depending on their insurance coverage. Our study also did not consider potential changes in healthcare policies, such as adoption of volume standards or regionalization of TJR to high volume centers [5] , which could limit the access to care and decrease the future demand. The above economic, policy, and scientific factors cannot be readily incorporated in the statistical model. Our study was also focused on the procedural trends in the U.S.; followup research may include an analysis of trends in other countries, though the availability of historical TJR trends in other countries may be limited. Nonetheless, these limitations in no way diminish the importance of conducting and regularly updating surgical projections to help guide future research, surgeon training, and public health policy decisions. Our study also incorporated a more conservative projection, which relied only on the future changes in population growth, while maintaining current rates of adoption of TJR. Despite these limitations, our current findings are expected to have implications in the private coverage and reimbursement of joint replacement procedures in the future, as patients less than 65 years of age are not typically covered by Medicare, which today funds the majority of total joint replacement procedures in the United States.

 We found the relative size of the young patient population for TJR has grown between 1993 and 2006. While 25% to 32% of primary or revision TJRs were performed in patients less than 65 years old in 1993, these proportions have increased to 40% to 46% in the most recent NIS data. The increasing trend in younger patients undergoing TJR has also been reported for different, but partly overlapping, historical periods. For example, Jain et al. reported that the proportion of primary TKA patients aged less than 60 years increased from 12.5% to 19.5% (+56%) between 1990-1993 and 1998-2000 [4] . In addition, for patients aged under 70 years, the proportion increased by 9% from 45.6% to 49.6%. Due to the difference in the stratification by age categories, we were unable to make a direct comparison with the data by Jain et al. [4] . However, our findings that the historical volume of TJR procedures in the younger patient population have been increasing is consistent with these previously reported trends.

 While we previously forecasted an increase in demand for primary hip and knee replacement in 2030 by 174% and 673% [6] , respectively, the current study underscores the contribution that young patients are expected to play in the Fig. 2A -B Historical incidence of primary total hip arthroplasty (A) and primary total knee arthroplasty (B) from 1993-2006, superimposed with previous projections [6] , and the updated projections from the current study. The dotted lines represent the 95% CI for the projections.

 future utilization of primary TJR surgery, if historical trends in prevalence continue into the future. The statistical modeling approach we have employed in the current and previous study fits a multivariate but linear Poisson regression model to the historical prevalence of TJR procedures. However, because the size of the population subgroups is free to change nonlinearly in the future based on the Census Bureau's projection, the actual projected incidence of surgical demand is therefore not constrained to be a linear function over time. The demand for primary hip and knee arthroplasty between 2004 and 2006 generally exceeded our previous projections, which employed an identical methodology. However, we are unable to judge, based on the limited window of new data for validation, whether a more complex modeling approach would provide a more reliable forecast of demand for surgical procedures.

 Our previous methodology provided a reasonable shortterm forecast of the demand for revision hip and knee surgeries between 2004 and 2006. In particular, for 2006, we observed a slight decrease in the estimated number of primary THA and TKA procedures compared to 2005 (Fig. 2 ), but this decrease fell within the uncertainty of the estimates.
datasets: tomaarsen/miriad-4.4M-split
pipeline_tag: sentence-similarity
library_name: sentence-transformers
metrics: cosine_accuracy@1, cosine_accuracy@3, cosine_accuracy@5, cosine_accuracy@10, cosine_precision@1, cosine_precision@3, cosine_precision@5, cosine_precision@10, cosine_recall@1, cosine_recall@3, cosine_recall@5, cosine_recall@10, cosine_ndcg@10, cosine_mrr@10, cosine_map@100
model-index: name: EmbeddingGemma-300m trained on the Medical Instruction and RetrIeval Dataset (MIRIAD)
results: task: type: information-retrieval
name: Information Retrieval
dataset: name: miriad eval 1kq 31kd
type: miriad-eval-1kq-31kd
metrics: type: cosine_accuracy@1
value: 0.822
name: Cosine Accuracy@1
verified: no, type: cosine_accuracy@3
value: 0.926
name: Cosine Accuracy@3
verified: no, type: cosine_accuracy@5
value: 0.945
name: Cosine Accuracy@5
verified: no, type: cosine_accuracy@10
value: 0.976
name: Cosine Accuracy@10
verified: no, type: cosine_precision@1
value: 0.822
name: Cosine Precision@1
verified: no, type: cosine_precision@3
value: 0.30866666666666664
name: Cosine Precision@3
verified: no, type: cosine_precision@5
value: 0.18900000000000003
name: Cosine Precision@5
verified: no, type: cosine_precision@10
value: 0.0976
name: Cosine Precision@10
verified: no, type: cosine_recall@1
value: 0.822
name: Cosine Recall@1
verified: no, type: cosine_recall@3
value: 0.926
name: Cosine Recall@3
verified: no, type: cosine_recall@5
value: 0.945
name: Cosine Recall@5
verified: no, type: cosine_recall@10
value: 0.976
name: Cosine Recall@10
verified: no, type: cosine_ndcg@10
value: 0.9026163565413016
name: Cosine Ndcg@10
verified: no, type: cosine_mrr@10
value: 0.8787773809523813
name: Cosine Mrr@10
verified: no, type: cosine_map@100
value: 0.8797433274658335
name: Cosine Map@100
verified: no, task: type: information-retrieval
name: Information Retrieval
dataset: name: miriad test 1kq 31kd
type: miriad-test-1kq-31kd
metrics: type: cosine_accuracy@1
value: 0.802
name: Cosine Accuracy@1
verified: no, type: cosine_accuracy@3
value: 0.907
name: Cosine Accuracy@3
verified: no, type: cosine_accuracy@5
value: 0.942
name: Cosine Accuracy@5
verified: no, type: cosine_accuracy@10
value: 0.963
name: Cosine Accuracy@10
verified: no, type: cosine_precision@1
value: 0.802
name: Cosine Precision@1
verified: no, type: cosine_precision@3
value: 0.30233333333333323
name: Cosine Precision@3
verified: no, type: cosine_precision@5
value: 0.18840000000000004
name: Cosine Precision@5
verified: no, type: cosine_precision@10
value: 0.09630000000000001
name: Cosine Precision@10
verified: no, type: cosine_recall@1
value: 0.802
name: Cosine Recall@1
verified: no, type: cosine_recall@3
value: 0.907
name: Cosine Recall@3
verified: no, type: cosine_recall@5
value: 0.942
name: Cosine Recall@5
verified: no, type: cosine_recall@10
value: 0.963
name: Cosine Recall@10
verified: no, type: cosine_ndcg@10
value: 0.886217623753175
name: Cosine Ndcg@10
verified: no, type: cosine_mrr@10
value: 0.8611063492063495
name: Cosine Mrr@10
verified: no, type: cosine_map@100
value: 0.862951336054453
name: Cosine Map@100
verified: no
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Created: 2025-09-16 13:41:59