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Abstract Alzheimer’s Disease (AD) significantly aggravates human dignity and quality of life. While newly approved amyloid immunotherapy has been reported, effective AD drugs remain to be identified. Here, we propose a novel AI-driven drug-repurposing method, DeepDrug, to identify a lead combination of approved drugs to treat AD patients. DeepDrug advances drug-repurposing methodology in four aspects. Firstly, it incorporates expert knowledge to extend candidate targets to include long genes, immunological and aging pathways, and somatic mutation markers that are associated with AD. Secondly, it incorporates a signed directed heterogeneous biomedical graph encompassing a rich set of nodes and edges, and node/edge weighting to capture crucial pathways associated with AD. Thirdly, it encodes the weighted biomedical graph through a Graph Neural Network into a new embedding space to capture the granular relationships across different nodes. Fourthly, it systematically selects the high-order drug combinations via diminishing return-based thresholds. A five-drug lead combination, consisting of Tofacitinib, Niraparib, Baricitinib, Empagliflozin, and Doxercalciferol, has been selected from the top drug candidates based on DeepDrug scores to achieve the maximum synergistic effect. These five drugs target neuroinflammation, mitochondrial dysfunction, and glucose metabolism, which are all related to AD pathology. DeepDrug offers a novel AI-and-big-data, expert-guided mechanism for new drug combination discovery and drug-repurposing across AD and other neuro-degenerative diseases, with immediate clinical applications.

Globalization, climate change, and political instability are increasing migration patterns across the world with millions of people, including children, adapting to new host nations (UNHCR, 2019). There is evidence that immigrant children have obstacles and influences in psychosocial development beyond language acquisition (Suárez-Orozco et al., 2008). Eriksonian Developmental Theory (Erikson, 1968) suggests as adolescents progress in typical identity maturation, they explore their future purpose in society while also establishing personal ethics. Further, Marcia et al. (1993) describe some adolescents who have actively sought personal ethic exploration, but cannot fully pursue a future purpose, as "Moratoriums." More broadly, the term "moratorium" can define a delay in legal motion, creating a waiting period (Miriam-Webster, 2024). This term aptly depicts the situation many undocumented youth face while waiting to live their lives fully in the United States regarding both legal status and identity development (Gonzales, 2011). This case study of five Latino immigrants, four being undocumented, asks adult respondents (aged 19-26) to reflect on moments of exclusion/inclusion in their secondary music classes through a set of open-ended questions. Using Quirkos software (2013), in vivo inductive coding revealed several themes found in transcribed interviews. Additionally, Suárez-Orozco et al. Integrative Risk and Resilience Model for Understanding the Adaptation of Immigrant-Origin Children and Youth (2018) provided the framework for deductive coding also revealing similar emergent themes. Findings show respondents felt included in music classes except regarding group travel. Several emergent themes encompassed identity, language acquisition, acculturation/enculturation, boundaries, and feelings. Research findings shed light on a clandestine population in the context of music education, general education, social-emotional learning, immigrant-specific adaptations, undocumented student's identity development, and meaningful music-making. This study gives some evidence that within the school immigrant adaptive microsystem, secondary music education programs may serve as a "nanosystem" for Moratoriums to feel safe to explore their future purpose actively without judgement, building resilience for the challenges that lie ahead.

BackgroundNoninvasive respiratory support modalities are common alternatives to mechanical ventilation in acute hypoxemic respiratory failure. However, studies historically compare noninvasive respiratory support to conventional oxygen rather than mechanical ventilation. In this study, we compared outcomes in patients with acute hypoxemic respiratory failure treated initially with noninvasive respiratory support to patients treated initially with invasive mechanical ventilation.MethodsThis is a retrospective observational cohort study between January 1, 2018 and December 31, 2019 at a large healthcare network in the United States. We used a validated phenotyping algorithm to classify adult patients (≥18 years) with eligible International Classification of Diseases codes into two cohorts: those treated initially with noninvasive respiratory support or those treated invasive mechanical ventilation only. The primary outcome was time-to-in-hospital death analyzed using an inverse probability of treatment weighted Cox model adjusted for potential confounders. Secondary outcomes included time-to-hospital discharge alive. A secondary analysis was conducted to examine potential differences between noninvasive positive pressure ventilation and nasal high flow.ResultsDuring the study period, 3177 patients met inclusion criteria (40% invasive mechanical ventilation, 60% noninvasive respiratory support). Initial noninvasive respiratory support was not associated with a decreased hazard of in-hospital death (HR: 0.65, 95% CI: 0.35-1.2), but was associated with an increased hazard of discharge alive (HR: 2.26, 95% CI: 1.92-2.67). In-hospital death varied between the nasal high flow (HR 3.27, 95% CI: 1.43-7.45) and noninvasive positive pressure ventilation (HR 0.52, 95% CI 0.25-1.07), but both were associated with increased likelihood of discharge alive (nasal high flow HR 2.12, 95 CI: 1.25-3.57; noninvasive positive pressure ventilation HR 2.29, 95% CI: 1.92-2.74).ConclusionsThese data show that noninvasive respiratory support is not associated with reduced hazards of in-hospital death but is associated with hospital discharge alive.

BackgroundPostoperative respiratory failure (PRF) is associated with increased hospital charges and worse patient outcomes. Reliable prediction models can help to guide postoperative planning to optimize care, to guide resource allocation, and to foster shared decision-making with patients.Research questionCan a predictive model be developed to accurately identify patients at high risk of PRF?Study design and methodsIn this single-site proof-of-concept study, we used structured query language to extract, transform, and load electronic health record data from 23,999 consecutive adult patients admitted for elective surgery (2014-2021). Our primary outcome was PRF, defined as mechanical ventilation after surgery of > 48 h. Predictors of interest included demographics, comorbidities, and intraoperative factors. We used logistic regression to build a predictive model and the least absolute shrinkage and selection operator procedure to select variables and to estimate model coefficients. We evaluated model performance using optimism-corrected area under the receiver operating curve and area under the precision-recall curve and calculated sensitivity, specificity, positive and negative predictive values, and Brier scores.ResultsTwo hundred twenty-five patients (0.94%) demonstrated PRF. The 18-variable predictive model included: operations on the cardiovascular, nervous, digestive, urinary, or musculoskeletal system; surgical specialty orthopedic (nonspine); Medicare or Medicaid (as the primary payer); race unknown; American Society of Anesthesiologists class ≥ III; BMI of 30 to 34.9 kg/m2; anesthesia duration (per hour); net fluid at end of the operation (per liter); median intraoperative FIO2, end title CO2, heart rate, and tidal volume; and intraoperative vasopressor medications. The optimism-corrected area under the receiver operating curve was 0.835 (95% CI,0.808-0.862) and the area under the precision-recall curve was 0.156 (95% CI, 0.105-0.203).InterpretationThis single-center proof-of-concept study demonstrated that a structured query language extract, transform, and load process, based on readily available patient and intraoperative variables, can be used to develop a prediction model for PRF. This PRF prediction model is scalable for multicenter research. Clinical applications include decision support to guide postoperative level of care admission and treatment decisions.

BackgroundDespite decades of research on predictors of extubation success, use of ventilatory support after extubation is common and 10-20% of patients require re-intubation. Proportional assist ventilation (PAV) mode automatically calculates estimated total work of breathing (total WOB). Here, we assessed the performance of total WOB to predict extubation failure in invasively ventilated subjects.MethodsThis prospective observational study was conducted in 6 adult ICUs at an academic medical center. We enrolled intubated subjects who successfully completed a spontaneous breathing trial, had a rapid shallow breathing index < 105 breaths/min/L, and were deemed ready for extubation by the primary team. Total WOB values were recorded at the end of a 30-min PAV trial. Extubation failure was defined as any respiratory support and/or re-intubation within 72 h of extubation. We compared total WOB scores between groups and performance of total WOB for predicting extubation failure with receiver operating characteristic curves.ResultsOf 61 subjects enrolled, 9.8% (n = 6) required re-intubation, and 50.8% (n = 31) required any respiratory support within 72 h of extubation. Median total WOB at 30 min on PAV was 0.9 J/L (interquartile range 0.7-1.3 J/L). Total WOB was significantly different between subjects who failed or were successfully extubated (median 1.1 J/L vs 0.7 J/L, P = .004). The area under the curve was 0.71 [95% CI 0.58-0.85] for predicting any requirement of respiratory support and 0.85 [95% CI 0.69-1.00] for predicting re-intubation alone within 72 h of extubation. Total WOB cutoff values maximizing sensitivity and specificity equally were 1.0 J/L for any respiratory support (positive predictive value [PPV] 70.0%, negative predictive value [NPV] 67.7%) and 1.3 J/L for re-intubation (PPV 26.3%, NPV 97.6%).ConclusionsThe discriminative performance of a PAV-derived total WOB value to predict extubation failure was good, indicating total WOB may represent an adjunctive tool for assessing extubation readiness. However, these results should be interpreted as preliminary, with specific thresholds of PAV-derived total WOB requiring further investigation in a large multi-center study.

ObjectiveThe Certified Flight Registered Nurse (CFRN) credential independently validates a registered nurse's advanced knowledge, skills, and abilities in the unique specialty of flight nursing. Introduced in 1993 and celebrating its 30th anniversary in July 2023, the CFRN is held by over 5,500 registered nurses. The purpose of the 2022 CFRN pulse survey was to better understand the ways CFRN-certified registered nurses value this national flight nursing specialty credential. The CFRN survey is a companion to the 2022 Certified Transport Registered Nurse pulse survey, which focused on the Certified Transport Registered Nurse critical care ground transport nursing credential.MethodsThe Board of Certification for Emergency Nursing e-mailed individuals in its database of CFRN credential holders and asked them to respond to a 14-question online survey between October 17, 2022, and November 8, 2022. Participation in the survey was voluntary. Of the 5,275 verified CFRN holders who received the survey, 992 responded, for a response rate of 18.8%. The survey instrument included discrete field and open-ended questions. Data were deidentified for analysis, and institutional review board exemption was received. Counts and percentages were reported, and descriptive statistics were used.ResultsThe highest percentage of flight nurses who responded have more than 10 years of experience in flight nursing (35.3%) and are employed by a stand-alone transport program (42.7%). Flight nurses reported they spent a mean of 70% of their work hours transporting via rotor wing aircraft, with a predominantly adult patient population. The top perceived benefits of being a CFRN-certified nurse were a sense of accomplishment and pride (90.7%) followed by flight physiology knowledge (85.4%), flight nursing clinical knowledge (83.4%), and confidence as a flight nurse (80.6%).ConclusionThe 2022 CFRN pulse survey identified current CFRN demographics, practice environments including transport percentage by mode and patient population types, and perceived benefits of the CFRN credential. The findings suggest CFRNs are very experienced, provide care for patients across the age continuum, and perceive multiple intrinsic and extrinsic benefits of CFRN certification, all of which are essential to safe, evidence-based advanced nursing practice in the unique, complex, autonomous, and dynamic flight environment.

Abstract Background Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. Methods Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days − 7, − 2, 21, and 28, and tick counts were performed on day − 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. Results On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P

Abstract Background Classic galactosemia (CG) is an inborn error of galactose metabolism caused by mutations in the GALT gene. Premature ovarian insufficiency (POI) is a later complication that affects 80% of women with CG due to a significant decline in ovarian reserve (primordial follicle pool). The definite mechanisms underlying the early onset of POI in CG patients are not fully understood. Methods In this study, we performed single‐nucleus RNA sequencing (snRNA‐seq) and spatial transcriptomics on ovary tissue biopsies from prepubertal girls diagnosed with CG to investigate dynamic changes in gene expression and altered signalling pathways in granulosa cells, oocytes, and stromal cells. Results We generated single‐nucleus and spatial transcriptomics atlas of human ovaries from prepubertal girls diagnosed with and without CG. snRNA‐seq profiling of the paediatric ovary revealed a diverse ovarian microenvironment with seven distinct major cell types. Our transcriptomic analysis revealed an increase in the expression of several endoplasmic reticulum stress and oxidative stress associated genes, which can promote apoptosis of granulosa cells in CG. PTEN/PI3K/AKT signalling, which is crucial for primordial follicle activation and survival was dysregulated as supported by upregulated PTEN transcripts and a significant reduction in phospho‐AKT levels in the granulosa cells and oocytes. We also found a marked increase in expression of phospho‐H2A.X, LC3A/B and CASP9 in the primordial follicles of CG ovaries suggesting DNA damage, autophagy, and accelerated follicular atresia. Furthermore, we noticed genes participating in extracellular matrix organisation, integrin and gap junction signalling, essential for structural support of the ovarian stroma were profoundly altered. Conclusions Our findings provide molecular insights into the dysregulated cellular signalling pathways essential for primordial follicle growth and survival that can explain the etiology of POI in CG patients. This study has implications in the development of future therapeutic interventions to preserve ovarian function and promote female reproductive health. Highlights Created a comprehensive single‐nucleus transcriptomic atlas and spatial landscape of paediatric ovary tissue from prepubertal girls diagnosed with classic galactosemia (CG). Our transcriptomic analysis revealed activation of genes associated with ER‐stress signalling, oxidative stress response and ATM signalling/DNA damage response as shown by significant increase in expression of p‐EIF2A, p‐H2A.X and LC3A/B in the primordial follicles of CG ovary. PTEN/PI3K/AKT signalling pathways was dysregulated evidenced by a significant reduction in phospho‐AKT expression in the primordial follicles of CG ovary, suggesting impaired follicle activation and survival.

IntroductionThe paralysis that occurs after a spinal cord injury, particularly during the early stages of post-lesion recovery (∼6 weeks), appears to be attributable to the inability to activate motor pools well beyond their motor threshold. In the later stages of recovery, however, the inability to perform a motor task effectively can be attributed to abnormal activation patterns among motor pools, resulting in poor coordination.MethodWe have tested this hypothesis on four adult male Rhesus monkeys (Macaca mulatta), ages 6-10 years, by recording the EMG activity levels and patterns of multiple proximal and distal muscles controlling the upper limb of the Rhesus when performing three tasks requiring different levels of skill before and up to 24 weeks after a lateral hemisection at C7. During the recovery period the animals were provided routine daily care, including access to a large exercise cage (5' × 7' × 10') and tested every 3-4 weeks for each of the three motor tasks.ResultsAt approximately 6-8 weeks the animals were able to begin to step on a treadmill, perform a spring-loaded task with the upper limb, and reaching, grasping, and eating a grape placed on a vertical stick. The predominant changes that occurred, beginning at ∼6-8 weeks of the recovery of these tasks was an elevated level of activation of most motor pools well beyond the pre-lesion level.DiscussionAs the chronic phase progressed there was a slight reduction in the EMG burst amplitudes of some muscles and less incidence of co-contraction of agonists and antagonists, probably contributing to an improved ability to selectively activate motor pools in a more effective temporal pattern. Relative to pre-lesion, however, the EMG patterns even at the initial stages of recovery of successfully performing the different motor tasks, the level of activity of most muscle remained higher. Perhaps the most important concept that emerges from these data is the large combinations of adaptive strategies in the relative level of recruitment and the timing of the peak levels of activation of different motor pools can progressively provide different stages to regain a motor skill.

Large animal contusion models of spinal cord injury are an essential precursor to developing and evaluating treatment options for human spinal cord injury. Reducing variability in these experiments has been a recent focus as it increases the sensitivity with which treatment effects can be detected while simultaneously decreasing the number of animals required in a study. Here, we conducted a detailed review to explore if head and neck positioning in a cervical contusion model of spinal cord injury could be a factor impacting the biomechanics of a spinal cord injury, and thus, the resulting outcomes. By reviewing existing literature, we found evidence that animal head/neck positioning affects the exposed level of the spinal cord, morphology of the spinal cord, tissue mechanics and as a result the biomechanics of a cervical spinal cord injury. We posited that neck position could be a hidden factor contributing to variability. Our results indicate that neck positioning is an important factor in studying biomechanics, and that reporting these values can improve inter-study consistency and comparability and that further work needs to be done to standardize positioning for cervical spinal cord contusion injury models.

Primary results from the phase 3 RESONATE-2 study demonstrated superior efficacy and tolerability with ibrutinib versus chlorambucil in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Here, we describe characteristics and outcomes of patients who received ibrutinib treatment for ≥5 years in RESONATE-2. Patients aged ≥65 years with previously untreated CLL/SLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5−0.8 mg/kg for ≤12 cycles (n = 133). Baseline characteristics in ibrutinib-randomized patients (n = 136) were generally similar between patients on ibrutinib treatment for ≥5 years (n = 79) versus those on treatment for

ObjectiveThe certified transport registered nurse (CTRN) credential independently validates a registered nurse's advanced knowledge, skills, and abilities in critical care ground transport nursing. After multiple years of mostly modest growth, the number of CTRNs surged in 2020 and 2021 and continues to post strong growth into 2022. The aim of the 2022 Certified Transport Registered Nurse Pulse Survey was to better understand the ways in which CTRN-certified registered nurses value this national ground transport specialty credential and gain insight into factors that may have contributed to the recent surge in CTRN certification.MethodsThe Board of Certification for Emergency Nursing e-mailed individuals in its database of CTRN credential holders and invited them to complete an 11-question online survey between March 15 and March 28, 2022. Participation in the survey was voluntary. Sixty-three of 297 verified CTRN holders who received the survey responded for a response rate of 21.2%. The survey instrument included discrete field and open-ended questions. Data were deidentified for analysis, and institutional review board exemption was received. Descriptive statistics were used, and counts and percentages are reported.ResultsThe highest percentage of respondents (42.9%) have 10 or more years of experience in ground transport nursing, and nearly half (46%) are employed by a stand-alone transport program. Forty-three percent of all respondents reported that ground transport makes up at least 50% of their current role, whereas one third (33.3%) indicated they do ground transport 100% of the time. Critical thinking (87.5%) in the ground transport environment, confidence as a ground transport nurse (87.5%), and a sense of accomplishment and pride (94.6%) were the top 3 perceived benefits of being a CTRN-certified nurse.ConclusionThe 2022 CTRN pulse survey identified current CTRN demographics, practice environments, and perceived benefits of the CTRN credential. The findings suggest CTRNs are highly experienced and perceive multiple intrinsic and extrinsic benefits of CTRN certification, many of which are essential to safe, evidence-based nursing practice in the autonomous, complex, and dynamic ground transport environment.

Rationale: Acute caustic ingestion from suicidal intent is not usual in emergency departments in developed countries. One of the substances commonly ingested by suicidal patients, phosphoric acid, tends to cause multi-system derangements. Patient’s Concern: A 41-year-old male patient presented with complaints of throat discomfort, severe generalized abdominal pain, and multiple episodes of hematemesis after ingesting a restroom cleaning solution. Diagnosis: Poisoning by acute caustic ingestion (containing

Despite the importance of biodiversity-ecosystem functioning (BEF) relationships in ecology and conservation, relatively little is known about how BEF relationships change across spatial scales. Theory predicts that change in BEF relationships with increasing spatial scale will depend on variation in species composition across space (β-diversity), but empirical evidence for this is limited. Moreover, studies have not quantified the direct and indirect role the environment plays in costructuring ecosystem functioning across spatial scales. We used 14 temperate-forest plots 1.4 ha in size containing 18,323 trees to quantify scale-dependence between aboveground tree biomass and three components of tree-species diversity-α-diversity (average local diversity), γ-diversity (total diversity), and β-diversity. Using structural-equation models, we quantified the direct effects of each diversity component and the environment (soil nutrients and topography), as well as indirect effects of the environment, on tree biomass across 11 spatial extents ranging from 400 to 14,400 m2 . Our results show that the relationship between β-diversity and tree biomass strengthened with increasing spatial extent. Moreover, β-diversity appeared to be a stronger predictor of biomass than α-diversity and γ-diversity at intermediate to large spatial extents. The environment had strong direct and indirect effects on biomass, but, in contrast to diversity, these effects did not strengthen with increasing spatial extent. This study provides some of the first empirical evidence that β-diversity underpins the scaling of BEF relationships in naturally complex ecosystems.

ObjectivesTo assess recent advances in interfacility critical care transport.Data sourcesPubMed English language publications plus chapters and professional organization publications.Study selectionManuscripts including practice manuals and standard (1990-2021) focused on interfacility transport of critically ill patients.Data extractionReview of society guidelines, legislative requirements, objective measures of outcomes, and transport practice standards occurred in work groups assessing definitions and foundations of interfacility transport, transport team composition, and transport specific considerations. Qualitative analysis was performed to characterize current science regarding interfacility transport.Data synthesisThe Task Force conducted an integrative review of 496 manuscripts combined with 120 from the authors' collections including nonpeer reviewed publications. After title and abstract screening, 40 underwent full-text review, of which 21 remained for qualitative synthesis.ConclusionsSince 2004, there have been numerous advances in critical care interfacility transport. Clinical deterioration may be mitigated by appropriate patient selection, pretransport optimization, and transport by a well-resourced team and vehicle. There remains a dearth of high-quality controlled studies, but notable advances in monitoring, en route management, transport modality (air vs ground), as well as team composition and training serve as foundations for future inquiry. Guidance from professional organizations remains uncoupled from enforceable regulations, impeding standardization of transport program quality assessment and verification.

We used viral intersectional tools to map the entire projectome of corticospinal neurons associated with fine distal forelimb control in Fischer 344 rats and rhesus macaques. In rats, we found an extraordinarily diverse set of collateral projections from corticospinal neurons to 23 different brain and spinal regions. Remarkably, the vast weighting of this "motor" projection was to sensory systems in both the brain and spinal cord, confirmed by optogenetic and transsynaptic viral intersectional tools. In contrast, rhesus macaques exhibited far heavier and narrower weighting of corticospinal outputs toward spinal and brainstem motor systems. Thus, corticospinal systems in macaques primarily constitute a final output system for fine motor control, whereas this projection in rats exerts a multi-modal integrative role that accesses far broader CNS regions. Unique structural-functional correlations can be achieved by mapping and quantifying a single neuronal system's total axonal output and its relative weighting across CNS targets.

IntroductionOlder adults experience less anxiety. We examined how memory of negative emotional images varied with age and may reflect age-related differences in anxiety.MethodsFifty-one adults, age 22-80 years, underwent imaging with a memory task where negative and neutral images were displayed pseudo-randomly. They were queried post-scan about the images inter-mixed with an equal number of images never displayed. Sensitivity (d’) and reporting bias (Z-score of false alarm rate; Z[FAR]) were quantified with signal detection theory.ResultsAge was negatively correlated with both Spielberg State Trait Anxiety Inventory (STAI) state score and d’ (negative – neutral) and positively with Z[FAR] (negative – neutral). However, STAI score and d’ or Z[FAR] (negative – neutral) were not significantly correlated. In whole-brain regression, STAI score was correlated with higher activity of the right middle/superior temporal gyri/temporal parietal junction (MTG/STG/TPJ) for “negative correct – incorrect” – “neutral correct – incorrect” trials. Further, the MTG/STG/TPJ activity (β) was also negatively correlated with age. Mediation analyses supported a complete mediation model of age → less anxiety → less MTG/STG/TPJ β.DiscussionTogether, the findings demonstrated age-related changes in negative emotional memory and how age-related reduction in anxiety is reflected in diminished temporoparietal cortical activities during encoding of negative emotional memory.

Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive. Antibiotic susceptibility to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates (n = 11) from an adult cystic fibrosis patient, over a 63 month period. Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with Clinical and Laboratory Standards Institute methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole. Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II and III) preceding this complete resistotype. The bacterium continued to display further antibiotic susceptibility heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V–XI). The Relative Resistance Index of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such a requirement for large numbers of colony picks combined with antibiotic susceptibility-related methodological problems creates a conundrum in biomedical science practice, in providing a robust assay that will capture antibiotic susceptibility variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in antibiotic susceptibility testing with Burkholderia cenocepacia. Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their cystic fibrosis patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.