Predictors of extended length of stay after unicompartmental knee arthroplasty.

PURPOSE: To identify factors that independently predict extended length of stay after unicompartmental knee arthroplasty (UKA) surgery (defined as length of stay longer than 3 days), and to identify factors predicting early post-operative complications. METHODS: A retrospective analysis of all patients undergoing UKA from January 2016-January 2019 at our institution was performed. Clinical notes were reviewed to determine the following information: Patient age (years), gender, American Society of Anesthesiologists (ASA) grade, weight (kg), height (meters), body mass index (BMI), co-morbidities, indication for surgery, surgeon, surgical volume, surgical technique (navigated or patient-specific instrumentation), implant manufacturer, estimated blood loss (ml), application of tourniquet during the surgery, application of drain, hospital length of stay (days) and surgical complications. RESULTS: Multivariate regression analysis showed that ASA 3-4 vs. ASA 1-2 [OR 4.4 (CI; 1.8-10.8, p = 0.001)] and a history of cardiovascular disease [OR 2.8 (CI; 1.4-5.5), p = 0.004)] were significant independent predictors of prolonged length of stay. Hosmer-Lemeshow goodness of fit of the model showed a p-value of 0.214. Nagelkerke R-Square was 0.2. For complications, multivariate regression analysis showed that ASA 3-4 vs. ASA 1-2 [OR 5.8 (CI; 1.7-20.7)] and high BMI (BMI >30) [OR 4.3 (CI; 1.1-17.1)] were significant independent predictors of complications. Hosmer-Lemeshow goodness of fit was 0.89 and Nagelkerke R-Square was 0.2. Patients treated with robotics (Navio) techniques had shorter length of stay median 51 h (IQR; 29-96) when compared to other techniques 72 h (IQR; 52-96), p = 0.008. CONCLUSION: Based on the results of our study, high ASA grade (≥3) appears to be the most important factor excluding eligibility for fast-track UKA. Any number of co-morbidities may increase ASA, but in and of themselves, apart from a history of cardiovascular disease, they should not be seen as contraindications. Appropriate patient selection, technical tools and details during the surgery could facilitate fast track surgery.

Should we routinely perform a post-operative hemoglobin check following unicompartmental knee arthroplasty?

OBJECTIVES: To study the significance of checking post-operative hemoglobin and hematocrit following unicompartmental knee arthroplasty (UKA). SETTING: Single center. Multiple surgeons. DESIGN: Retrospective case series. Level of evidence IV. MATERIALS AND METHODS: Following institutional approval, a retrospective analysis of all patients undergoing UKA at our level one academic university hospital was conducted. Operative records of all patients undergoing primary UKA were reviewed between March 2016 and March 2019. Patients' pre-operative hemoglobin and hematocrit, BMI, co-morbidities, application of tourniquet, tourniquet time, administration of tranexamic acid, need for post-operative blood transfusion, hospital length of stay, complications, and re-admission were all recorded. Blood loss was estimated using the post-operative hematocrit. RESULTS: A total number of 155 patients were included. There were 70 females (45%) and 85 males (55%). The mean age was 66 ±â€¯10 years. Median pre-op blood volume was 4700 mLs (interquartile range (IQR); 4200-5100). Median blood loss was 600 mLs (IQR; 400-830). Mean pre-op hemoglobin was 135 ±â€¯14 g/L and mean post-op hemoglobin was 122 ±â€¯13 g/L. No patient had a post-op hemoglobin under 80 g/L (range 93-154). No patients in our study needed transfusion. CONCLUSION: The results of our study indicated that post-operative hemoglobin and hematocrit check proved unnecessary in all of our patients and could have been omitted from post-operative routines. We conclude that routine post UKA check of hemoglobin and hematocrit can be avoided and be saved for special circumstances depending on patient's physiology.

Development and content validation of measures assessing adherence barriers and behaviors for use in clinical care.

BACKGROUND: Providers are often unaware of poor adherence to prescribed medications for their patients with chronic diseases. OBJECTIVE: To develop brief, computer-administered patient-reported measures in English and Spanish assessing adherence behaviors and barriers. Design, Participants, and Main Measures: Item pools were constructed from existing measures of medication adherence behaviors and barriers, which informed development of a patient concept elicitation interview guide to identify medication adherence behavior and barrier-related concepts. Two hundred six patients either living with HIV (PLWH) or without were interviewed. Interviews were coded, concepts matched to item pool content, and new items were developed for novel concepts. A provider/investigator team highlighted clinically relevant items. Cognitive interviews were conducted with patients on final candidate items (n = 37). The instruments were administered to 2081 PLWH. KEY RESULTS: Behavioral themes from concept elicitation interviews included routines incorporating time of day, placement, visual cues, and intentionality to miss or skip doses. Barrier themes included health-related (e.g. depressed mood, feeling ill), attitudes/beliefs (e.g., need for medication), access (e.g., cost/insurance problems), and circumstantial barriers (e.g., lack of privacy, disruption of daily routine). The final instruments included 6 behavior items, and 1 barrier item with up to 23 response options. PLWH endorsed a mean (SD) of 3.5 (1.1) behaviors. The 201 PLWH who missed ≥2 doses in the previous week endorsed a mean (SD) of 3.1 (2.5) barriers. The intraclass correlation coefficient (ICC) for the numbers of behaviors endorsed in 61 PLWH after 4-16 days was 0.54 and for the number of barriers for the 20 PLWH with ≥2 missed doses the ICC was 0.89, representing fair and excellent test-retest reliability. CONCLUSION: Measures of medication adherence behaviors and barriers were developed for use with patients living with chronic diseases focusing on clinical relevance, brevity, and content validity for use in clinical care.

Circumstances Surrounding High-risk Sexual Experiences Among Primary Care Patients Living With and Without HIV.

INTRODUCTION: Rates of sexually transmitted infection (STI) are rising in the USA, yet STI risk remains under-addressed by providers, even in HIV care, and with high-risk patients. We interviewed primary care patients living with and without HIV regarding circumstances surrounding sexual risk behavior to identify opportunities for providers to address and reduce STI risk. METHODS: We conducted semi-structured 1:1 interviews with patients living with and without HIV reporting ≥ 1 sex partner and varying STI exposure risk in the past 12 months from four geographically diverse US HIV and primary care clinics. We audio-recorded, transcribed, and coded interviews by circumstance type, using double-coding to ensure inter-coder reliability. We used Fisher's exact and T tests to determine associations with demographic/risk factors. RESULTS: Patients (n = 91) identified a mean of 3 of 11 circumstances. These included substance use (54%), desire for physical/emotional intimacy (48%), lack of HIV/STI status disclosure (44%), psychological drivers (i.e., coping, depression; 38%), personal dislike of condoms (22%), partner condom dislike/refusal (19%), receiving payment for sex (13%), and condom unavailability (9%). Higher proportions of those who were high STI-exposure risk patients, defined as those with ≥ 2 sex partners in the past 3 months reporting never or sometimes using condoms, reported disliking condoms (p = .006); higher proportions of the high-risk and moderate-risk (≥ 2 partners and condom use "most of the time") groups reported substance use as a circumstance (p = .04). CONCLUSION: Circumstances surrounding perceived STI exposure risk were diverse, often overlapping, and dependent on internal, environmental, and partner-related factors and inadequate communication. Meaningful care-based interventions regarding HIV/STI transmission behavior must address the diversity and interplay of these factors.

Initial development and pilot testing of observer-reported outcomes (ObsROs) for children with cystic fibrosis ages 0-11years.

PURPOSE: Patient-reported outcomes are important clinical trial endpoints. Young children may not be able to reliably report on how they feel or function, so observer-reported outcomes (ObsROs) may be more appropriate for them. The purpose of this study was to develop and pilot field test electronic parent-reported observational instruments for children with cystic fibrosis (CF) 0-6 and 7-11years of age. METHODS: We performed concept elicitation interviews with parents of children with CF ≤11years of age to elicit the respiratory signs they could observe at baseline and during an acute respiratory illness. The resulting instruments were refined based on interviews with parents and clinicians. We conducted a pilot field test to evaluate test-retest reliability and the ability of items to distinguish well and sick periods. RESULTS: The instruments consist of 17 items assessing respiratory signs and observable CF-related impacts. Test-retest reliability was acceptable for both age groups but discrimination was low for ages 7-11, likely reflecting less direct observation of older children by their parents. CONCLUSIONS: An ObsRO for children with CF ages 0-6 appears promising, while self-report may be more appropriate for children >6years of age. Next steps for the 0-6year old instrument will be utilizing it as an exploratory endpoint in clinical trials to enable item reduction, scale development, and further reliability and validity testing. Ultimately, this ObsRO could be a promising endpoint for early intervention trials in young children with CF.

Medication understanding among patients living with multiple chronic conditions: Implications for patient-reported measures of adherence.

BACKGROUND: Low health literacy is associated with poor medication adherence and poor health outcomes. Limited understanding of prescribed medications may decrease validity of patient-reported adherence measures. OBJECTIVES: To assess knowledge of names and purposes of prescribed medications among patients with multiple chronic conditions. METHODS: Individual interviews were conducted with a convenience sample of patients from six U.S. primary care clinics. Participants (n = 57) were English and/or Spanish-speaking patients prescribed 3+ medications for chronic conditions, for which non-adherence may lead to disability or death. In individual interviews, patients were asked to name their medications, explain the purpose of each, and to explain how they distinguish them from one another. Interviews were audio recorded, transcribed, and coded; coded content was quantified by 1) whether or not the patient could name medications; 2) method of categorizing medications; 3) whether or not the purpose of the medication was understood. Descriptive statistics were compiled using Fisher's exact test to determine the relationship between patient knowledge and medication characteristics. RESULTS: Thirty percent of patients could not name at least one of their medications; 19% did not know their purpose; 30% held misconceptions about the purpose of one or more medications. There was no significant difference in ability to name medications or state their medication's purpose between patients using medi-sets, pre-packaged rolls, or blister packs, and patients who stored pills in their original containers (p = 0.56 and p = 0.73, respectively), or across demographic groups (p = 0.085 to 0.767). CONCLUSIONS: Many patients demonstrated difficulty identifying the name and purpose of prescribed medications; this did not differ by demographic group or medication storage type. Patients may benefit from routine review of medications with their provider in order to improve health literacy, outcomes, and patient-reported adherence measurement.

Validity assessment of the PROMIS fatigue domain among people living with HIV.

PURPOSE: To evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care. METHODS: Cross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics. RESULTS: We analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS. CONCLUSIONS: The PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden.

Systematic review: patient-reported outcome measures in coeliac disease for regulatory submissions.

BACKGROUND: New therapeutics are moving into phase 3 clinical trials for the treatment of coeliac disease, a condition with no established therapies other than gluten-free diet. These trials will require a meaningful, validated and fit for purpose patient-reported outcome measure (PROM) to quantify the symptomatic improvement of patients. AIM: To evaluate existing PROMs for suitability in a Food and Drug Administration (FDA) approval trial for a coeliac disease therapeutic. METHOD: We performed a systematic search in five online databases (MedLine, EmBase, Web of Science, CENTRAL, CINAHL) for studies that enrolled patients with coeliac disease and used PROMs. Studies included in this review had to measure some PROM concept, be patient administered and based upon a previously validated instrument with published measurement properties. RESULTS: Our literature search identified 2706 unique records of which 199 ultimately qualified for abstraction. The majority of PROMs used in studies of coeliac disease was generic and did not measure numerous symptoms or concerns of interest to patients. Four PROMs were found to contain appropriate content for use in an FDA trial: the coeliac disease-specific modification of the Gastrointestinal Symptoms Rating Scale (CeD-GSRS), Psychological General Well-Being Index (PGWB), the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient Reported Outcome (CeD-PRO). The GSRS and PGWB are most often used together and are two of the most extensively used measures in coeliac disease. The CDSD and CeD-PRO were developed exclusively for trials in coeliac disease but have much less published information on their measurement properties. CONCLUSIONS: While we did not find PROMs that currently meet the stated expectations of the FDA for regulatory purposes, four PROMs (CeD-GSRS, PGWB, CDSD and CeD-PRO) appear to contain appropriate content and with modest additional validation work could meet scientific standards for valid and sensitive measures of disease and treatment outcome. Specifically, what is needed for these instruments is an understanding of how sensitive they are to real changes in-patient condition, how stable they are over a period of time when health status should not have changed (test-retest reliability) as well as how they correlate with other measures of patient functioning such as intestinal biopsy. All of these objectives could feasibly be accomplished over a short cohort study of patients with biopsy-defined coeliac disease undergoing gluten challenge.

Mode of communication, perceived level of understanding, and perceived quality of life in youth who are deaf or hard of hearing.

Given the important role of parent-youth communication in adolescent well-being and quality of life, we sought to examine the relationship between specific communication variables and youth perceived quality of life in general and as a deaf or hard-of-hearing (DHH) individual. A convenience sample of 230 youth (mean age = 14.1, standard deviation = 2.2; 24% used sign only, 40% speech only, and 36% sign + speech) was surveyed on communication-related issues, generic and DHH-specific quality of life, and depression symptoms. Higher youth perception of their ability to understand parents' communication was significantly correlated with perceived quality of life as well as lower reported depressive symptoms and lower perceived stigma. Youth who use speech as their single mode of communication were more likely to report greater stigma associated with being DHH than youth who used both speech and sign. These findings demonstrate the importance of youths' perceptions of communication with their parents on generic and DHH-specific youth quality of life.

Weight loss and changes in generic and weight-specific quality of life in obese adolescents.

PURPOSE: To investigate how weight loss correlates with changes in generic and weight-specific quality of life (QoL). METHODS: Youth generic (YQOL-S) and weight-specific instruments (YQOL-W) from 133 youth age 11-19 were analyzed at the beginning and end of 4-week immersion camp sessions known to produce weight loss. Paired samples t tests were used to test mean difference between baseline and final Body Mass Index (BMI) and YQOL-S and YQOL-W scores. YQOL-S and YQOL-W scores were transformed to values between 0 and 100, with higher values indicating better QOL. Cohen's d effect sizes were calculated to assess magnitude of effects. Percent weight loss (as % of baseline weight), change in BMI (baseline kg/m²-follow-up kg/m²), and change in % overweight ((BMI-50th% BMI for age and sex)/50th% BMI for age and sex × 100) were calculated. Multiple regressions were used to model final YQOL scores in the 11-14 and 15-19 age groups as functions of each measure of weight change, sex, age, and baseline YQOL score. RESULTS: Youth experienced significant reductions in BMI (Mean change = 3.7, SD = 1.4, t = 34.1, P < 0.001) and in the other measures of weight change. YQOL-S and YQOL-W scores improved significantly (P < 0.001), and effect sizes were 0.61 and 0.66, respectively. CONCLUSION: Changes in generic and weight-specific quality of life scores are associated with weight loss. The weight-specific measure is slightly more sensitive to weight changes; however, when controlling for modifiers, the YQOL-W remained significantly associated with weight loss, while the generic QoL measure did not.

Development of a quality of life instrument for pediatric gastroesophageal reflux disease: qualitative interviews.

OBJECTIVES: Antireflux procedures (ARP) are commonly performed in children and there is no disease-specific quality of life (QOL) instrument for gastroesophageal reflux (GERD) in children. The aim of this study was to identify the relevant domains for developing such an instrument. These domains will be validated in a future study. PATIENTS AND METHODS: Parents of 19 patients (age 2 months-18 years) clinically diagnosed with GERD were recruited to complete semistructured interviews. Seven patients with adequate verbal skills were also interviewed. Patients were treated medically (13 patients) or with an ARP (6 patients). The interviews were analyzed using grounded theory. RESULTS: GERD affects QOL through the following domains: symptom severity, feeding quality, sleep quality, hygiene, growth and development, social quality, self-image, coping skills, family QOL, health care usage, and impact of ARP. A greater-than-expected effect on parental QOL and remarkable use of accommodation were identified. CONCLUSIONS: A pediatric GERD-specific instrument cannot rely on QOL perception alone, but must address broadly the impact of the disease and the effect of coping skills on the child and his or her family in their activities of daily living and interaction with society. We have identified reproducible domains that will serve as the foundation for such an instrument.

Patient-reported respiratory symptoms in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) specific patient-derived and reported symptom tools are critical steps toward evaluating the outcomes of new therapies for CF. METHODS: We conducted 25 in-depth qualitative interviews using the Day Reconstruction Method and 9 cognitive interviews at two CF programs, the University of Washington and Seattle Children's Hospital and Regional Medical Center. The interviews were audio-recorded and transcribed, and then coded and analyzed for themes relating to pulmonary symptoms and related psychosocial impacts. RESULTS: Six pulmonary symptoms were identified as central to CF: cough, sputum production, wheeze, chest tightness, difficulty breathing/shortness of breath, and fever. Emotional impacts included frustration, sadness/depression, irritability, worry, difficulty sleeping; while activity impacts included time spent sitting or lying down, reduction of usual activities, and missing school or work. In all, 8 symptom items, 4 emotional impacts items, and 4 activity impacts were selected for inclusion on a new daily diary. We also assessed triggers for seeking care. CONCLUSIONS: Using a qualitative inductive methodology, we have obtained patient centered data regarding pulmonary symptoms and burdens and have created a novel patient reported outcome measure for CF. Future studies will assess the validity of the instruments.

Remote sensing-based predictors improve distribution models of rare, early successional and broadleaf tree species in Utah.

Compared to bioclimatic variables, remote sensing predictors are rarely used for predictive species modelling. When used, the predictors represent typically habitat classifications or filters rather than gradual spectral, surface or biophysical properties. Consequently, the full potential of remotely sensed predictors for modelling the spatial distribution of species remains unexplored. Here we analysed the partial contributions of remotely sensed and climatic predictor sets to explain and predict the distribution of 19 tree species in Utah. We also tested how these partial contributions were related to characteristics such as successional types or species traits.We developed two spatial predictor sets of remotely sensed and topo-climatic variables to explain the distribution of tree species. We used variation partitioning techniques applied to generalized linear models to explore the combined and partial predictive powers of the two predictor sets. Non-parametric tests were used to explore the relationships between the partial model contributions of both predictor sets and species characteristics.More than 60% of the variation explained by the models represented contributions by one of the two partial predictor sets alone, with topo-climatic variables outperforming the remotely sensed predictors. However, the partial models derived from only remotely sensed predictors still provided high model accuracies, indicating a significant correlation between climate and remote sensing variables. The overall accuracy of the models was high, but small sample sizes had a strong effect on cross-validated accuracies for rare species.Models of early successional and broadleaf species benefited significantly more from adding remotely sensed predictors than did late seral and needleleaf species. The core-satellite species types differed significantly with respect to overall model accuracies. Models of satellite and urban species, both with low prevalence, benefited more from use of remotely sensed predictors than did the more frequent core species.Synthesis and applications. If carefully prepared, remotely sensed variables are useful additional predictors for the spatial distribution of trees. Major improvements resulted for deciduous, early successional, satellite and rare species. The ability to improve model accuracy for species having markedly different life history strategies is a crucial step for assessing effects of global change.

Quality of life and health-risk behaviors among adolescents.

PURPOSE: To assess the association between health-risk behaviors and self-perceived quality of life among adolescents METHODS: A sample of 2801 students (957 seventh and eighth graders and 1844 ninth through twelfth graders) completed the Teen Assessment Survey (TAP) and the surveillance module of the Youth Quality of Life Instrument (YQOL-S). TAP responses were used to determine health-risks related to tobacco use, alcohol use, illicit drug use, and high risk sexual behavior. Separate multivariate analyses of variance showed mean differences in contextual and perceptual items of the YQOL-S for each health-risk behavior. Differences among engagers (adolescents who often engage), experimenters (occasionally engage), and abstainers (never engage) in the health-risk behavior were evaluated by gender and junior/senior high school groups. RESULTS: In general, adolescent abstainers reported higher quality of life (QoL) than engagers and experimenters on YQOL-S items. Adolescents who engaged in multiple risk behaviors scored even lower than those who engaged in only one health-risk behavior. Experimenters tended to rate their QoL more similar to that of abstainers than to that of engagers. CONCLUSIONS: The framework of QoL proved useful in the evaluation of adolescents' engagement in health-risk behaviors. Additionally, assessing the areas of QoL that differ between the groups may provide information for planning interventions aimed at risk reduction among engagers and experimenters.

Abnormal cardiovascular responses to exercise during the development of obesity in dogs.

This study examined the control of cardiovascular dynamics in response to exercise during the development of obesity in dogs. Left atrial pressure (LAP), mean arterial pressure, and cardiac output (CO) were determined both at rest and in response to treadmill exercise (5.6 km/h, 10% grade) first during a control, lean state and then, once a week while the dogs were maintained on a high fat diet (HFD) for 4 weeks. Body weight increased from 22.8 +/- 1.1 to 33.1 +/- 2.0 kg after 4 weeks of HFD. The dogs developed mild hypertension with increases in resting CO, heart rate, and LAP. The response to exercise was characterized by a decrease in LAP when the dogs were lean and, in contrast, by a dramatic increase in LAP during the development of obesity. In addition, after the third week, the dogs could no longer maintain exercise at the original level. These results suggest that abnormal left ventricular function may occur very early during the development of canine obesity.

Transcatheter occlusion of Blalock-Taussig shunts: technical options.

PURPOSE: This review of findings in children undergoing transcatheter shunt occlusion was carried out to describe and compare the results of four different embolization techniques. PATIENTS AND METHODS: A retrospective review of clinical, radiologic, and cardiac catheterization records was carried out for 18 consecutive pediatric patients referred for Blalock-Taussig shunt occlusion at one institution. Technical aspects included the use of three devices--steel wire/fiber coils, detachable latex balloons, and ductal occlusion devices--and four techniques--direct transarterial placement, transarterial placement with proximal or with distal flow control, and transvenous delivery. RESULTS: Occlusion of the shunt was attempted in 17 patients (mean age, 6.2 years). Shunt occlusion was successful in 14 patients. Embolization of a device into the pulmonary circulation occurred in five patients, and was most frequent with transarterial delivery without flow control or with proximal flow control (in four of six). Transarterial occlusion with distal flow control and transvenous delivery of ductal occluder devices were the most reliable methods of occluding shunts without distal stenosis, with success in eight of nine cases with the former technique and all of three with the latter technique. CONCLUSIONS: Transarterial embolization of Blalock-Taussig shunts carries a risk of device embolization to the pulmonary circulation; this is best avoided by the use of distal flow control or transvenous placement of a ductal occlusion device.

Sweet's syndrome with multifocal sterile osteomyelitis.

Sweet's syndrome is a rare condition characterized by fever, leukocytosis, dense dermal infiltration of leukocytes, and painful indurated cutaneous plaques. We describe a 23-month-old male infant with the typical cutaneous manifestations of Sweet's syndrome and painful extremities that limited ambulation. Evaluation revealed multifocal sterile osteomyelitis of both tibia. After the institution of systemic corticosteroid therapy, the patient's symptoms resolved, and bone scans normalized. After one year of follow-up, the patient has intermittent recrudescences that resolve during corticosteroid therapy. Sterile multifocal osteomyelitis represents another clinical manifestation of Sweet's syndrome.

Xanthine dehydrogenase from Drosophila melanogaster: a comparison of the kinetic parameters of the pure enzyme from two wild-type isoalleles differing at a putative regulatory site.

Xanthine dehydrogenase (XDH) from Drosophila melanogaster has been purified to homogeneity by immunoaffinity chromatography, and its kinetic parameters determined. Drosophila XDH exhibits ordered binding for substrate and NAD+, analogous to the corresponding enzymes from vertebrate sources. The wild-type enzyme exhibits a Km for xanthine of 2.4 X 10(-5) M, and for NAD+ of 4.0 X 10(-5) M. XDH purified from a genetic variant exhibiting elevated levels of enzyme activity has similar kinetic constants. The results provide further evidence that the site of variation in the latter strain results in higher steady state numbers of XDH molecules per fly.