Diagnostic accuracy of inflammatory markers in adults with suspected central nervous system infections.

OBJECTIVES: We aimed to determine diagnostic accuracy of inflammatory markers in plasma and cerebrospinal fluid (CSF) for the diagnosis of central nervous system (CNS) infections and specifically bacterial meningitis. METHODS: We analyzed 12 cytokines, chemokines, and acute phase reactants in CSF and plasma of 738 patients with suspected neurological infection included in a multicenter prospective cohort. We determined diagnostic accuracy for predicting any CNS infection and bacterial meningitis. RESULTS: We included 738 episodes between 2017 and 2022, split into a derivation (n = 450) and validation cohort (n = 288). Of these patients, 224 (30%) were diagnosed with CNS infection, of which 81 (11%) with bacterial meningitis, 107 (14%) with viral meningitis or encephalitis, and 35 patients (5%) with another CNS infection. Diagnostic accuracy of CRP, IL-6, and Il-1ß in CSF was high, especially for diagnosing bacterial meningitis. Combining these biomarkers in a multivariable model increased accuracy and provided excellent discrimination between bacterial meningitis and all other disorders (AUC = 0.99), outperforming all individual biomarkers as well as CSF leukocytes (AUC = 0.97). When applied to the population of patients with a CSF leukocyte count of 5-1000 cells/mm3, accuracy of the model also provided a high diagnostic accuracy (AUC model = 0.97 vs. AUC CSF leukocytes = 0.80) with 100% sensitivity and 92% specificity. These results remained robust in a temporal validation cohort. CONCLUSIONS: Inflammatory biomarkers in CSF are able to differentiate CNS infections and especially bacterial meningitis from other disorders. When these biomarkers are combined, their diagnostic accuracy exceeds that of CSF leukocytes alone and as such these markers have added value to current clinical practice.

CRISPR/Cas9 deletion of MIR155HG in human T cells reduces incidence and severity of acute GVHD in a xenogeneic model.

ABSTRACT: Acute graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Using preclinical mouse models of disease, previous work in our laboratory has linked microRNA-155 (miR-155) to the development of acute GVHD. Transplantation of donor T cells from miR-155 host gene (MIR155HG) knockout mice prevented acute GVHD in multiple murine models of disease while maintaining critical graft-versus-leukemia (GVL) response, necessary for relapse prevention. In this study, we used clustered, regularly interspaced, short palindromic repeats (CRISPR)/Cas9 genome editing to delete miR-155 in primary T cells (MIR155HGΔexon3) from human donors, resulting in stable and sustained reduction in expression of miR-155. Using the xenogeneic model of acute GVHD, we show that NOD/SCID/IL2rγnull (NSG) mice receiving MIR155HGΔexon3 human T cells provide protection from lethal acute GVHD compared with mice that received human T cells with intact miR-155. MIR155HGΔexon3 human T cells persist in the recipients displaying decreased proliferation potential, reduced pathogenic T helper-1 cell population, and infiltration into GVHD target organs, such as the liver and skin. Importantly, MIR155HGΔexon3 human T cells retain GVL response significantly improving survival in an in vivo model of xeno-GVL. Altogether, we show that CRISPR/Cas9-mediated deletion of MIR155HG in primary human donor T cells is an innovative approach to generate allogeneic donor T cells that provide protection from lethal GVHD while maintaining robust antileukemic response.

A Phase 2 Trial of Ibrutinib and Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma.

BACKGROUND: Relapsed or refractory classical Hodgkin lymphoma (cHL) remains a difficult treatment challenge. Although checkpoint inhibitors (CPI) have provided clinical benefit for these patients, responses are generally not durable, and progression eventually occurs. Discovering combination therapies which maximize the immune response of CPI therapy may overcome this limitation. We hypothesized that adding ibrutinib to nivolumab will lead to deeper and more durable responses in cHL by promoting a more favorable immune microenvironment leading to enhanced T-cell-mediated anti-lymphoma responses. METHODS: We conducted a single arm, phase II clinical trial testing the efficacy of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who had received at least one prior line of therapy. Prior treatment with CPIs was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for up to 16 cycles. The primary objective was complete response rate (CRR) assessed per Lugano criteria. Secondary objectives included overall response rate (ORR), safety, progression free survival (PFS), and duration of response (DoR). RESULTS: A total of 17 patients from two academic centers were enrolled. The median age of all patients was 40 (range 20-84). The median number of prior lines of treatment was five (range 1-8), including 10 patients (58.8%) who had progressed on prior nivolumab therapy. Most treatment related events were mild (

Fatigue Performance of Type I and Type II Fibre Bragg Gratings Fabricated by Femtosecond Laser Inscription through the Coating.

Strain sensing technology using fibre Bragg grating (FBG) sensors is an attractive capability for aerospace structural health monitoring (SHM) and assessment because they offer resistance to harsh environments, low maintenance, and potential for high density and high strain sensing. The development of FBG inscription techniques through the fibre polymer coating using infrared (IR) lasers has overcome the mechanical weaknesses introduced by removal of the fibre coating, which is typically required for conventional UV laser inscription of FBGs. Type I and Type II femtosecond gratings are fabricated using through-coating inscription techniques, but the higher laser energy used for Type II gratings damages the glass fibre core, impacting mechanical performance. This paper investigates the fatigue performance of Type I and Type II through-coating FBG sensors with different fibre geometries and photosensitisation approaches to evaluate their overall reliability and durability, with a view to assess their performance for potential use in civil and defence SHM applications. The fatigue performance of FBG sensors was assessed under high-strain and high-frequency mechanical loading conditions by using a custom-designed electro-dynamically actuated loading assembly. In addition, pre- and post-fatigue microscopic analyses and high-resolution reflection spectrum characterisation were conducted to investigate the failure regions of the fibres and the effect of fatigue loading on reflection spectrum features. As expected, Type I gratings had a significantly higher fatigue life compared to Type II gratings. However, Type II gratings performed significantly better than conventional UV laser-inscribed FBGs and electrical foil strain gauges. Type II gratings withstand higher temperatures, and are therefore more suitable for application in harsh environments.

Ultramini-percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of 10-30 mm calculi: a randomized controlled trial.

The surgical management of renal stones 10-30 mm is usually performed with percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Standard form of percutaneous nephrolithotomy has paved the way for miniaturized PCNL in many centres. We wanted to evaluate the efficacy, safety and the cost-effectiveness of ultramini-percutaneous nephrolithotomy (UMP) versus RIRS in the treatment of renal stones with stone burden 10-30 mm. Patients with renal stone burden 10-30 mm were prospectively randomized into either UMP or RIRS. The demographic data, stone characteristic, operative time and cost of the equipment were recorded. The stone free status, analgesic requirement, deterioration of the renal function and hemoglobin and the postoperative complications as per Clavein-Dindo grade were recorded. One hundred and fifty patients met inclusion criteria. Out of these 98 underwent UMP and 46 RIRS. Six withdrew the consent before the procedure. Mean stone size was comparable in either of the groups. Mean laser time and stone extraction time was significantly less for UMP compared to RIRS (41.17 min versus 73.58 min p < 0.0001). Mean consumable costs in the UMP group were considerably less at US$45.73 compared to the RIRS group at $423.11 (p < 0.0001). The stone free rates at 1 month of follow-up were 100% for UMP group and 73% for RIRS group. There were insignificant changes to mean hemoglobin and glomerular filtration rate (GFR) in all patients and the average length of the stay was similar in both the groups. The postoperative complications revealed Grade I and II rate of 10% in the UMP group and 35% in the RIRS group, respectively. We concluded that UMP to be safe, effective and more economical to the RIRS for renal stones up to 3 cm in size.Trial registered with ISRCTN registry ID ISRCTN20935105, Retrospective.

Effect of shoe modifications on biomechanical changes in basketball: A systematic review.

Shoe modifications are suggested to reduce the risks of injuries and improve sports performance in basketball. This review aimed to critically evaluate the effect of different basketball shoe modifications on biomechanical changes in basketball movements. Searches of four major databases for biomechanics studies which evaluated footwear construction/material in basketball yielded 442 records. After duplicates were removed and exclusion/inclusion criteria applied to the titles and abstracts, 20 articles remained for further quality assessment. Two reviewers independently confirmed 17 articles (n = 340 participants), with 95.5% of agreement between judgements, which were included for review. The results were categorised based on the following shoe modifications: (a) cushioning, (b) midsole hardness, (c) collar height, (d) outsole traction component, (e) forefoot bending stiffness and (f) shoe mass that influence lower limb biomechanics. The included articles revealed that 1) better shoe cushioning or softer midsole is related to better impact attenuation in passive/unanticipated situations, 2) high shoe collars are effective to improve ankle stability in jumping and cutting tasks, 3) increased shoe traction and forefoot bending stiffness can improve basketball jump, sprint and/or cut performances and 4) lighter shoe mass results in better jump and/or cut performances when the shoe mass is known.

The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition.

α-Synuclein (αS) is a presynaptic disordered protein whose aberrant aggregation is associated with Parkinson's disease. The functional role of αS is still debated, although it has been involved in the regulation of neurotransmitter release via the interaction with synaptic vesicles (SVs). We report here a detailed characterisation of the conformational properties of αS bound to the inner and outer leaflets of the presynaptic plasma membrane (PM), using small unilamellar vesicles. Our results suggest that αS preferentially binds the inner PM leaflet. On the basis of these studies we characterise in vitro a mechanism by which αS stabilises, in a concentration-dependent manner, the docking of SVs on the PM by establishing a dynamic link between the two membranes. The study then provides evidence that changes in the lipid composition of the PM, typically associated with neurodegenerative diseases, alter the modes of binding of αS, specifically in a segment of the sequence overlapping with the non-amyloid component region. Taken together, these results reveal how lipid composition modulates the interaction of αS with the PM and underlie its functional and pathological behaviours in vitro.

Single-centre Experience of Patients with Metastatic Urothelial Cancer Treated with Chemotherapy Following Immune Checkpoint Inhibition.

There are few data on outcomes for patients with metastatic urothelial carcinoma (MUC) who receive chemotherapy (CT) after progression on immune checkpoint inhibitors (ICIs). We carried out a retrospective single-centre analysis of MUC patients who progressed after ICI and then received CT. Patients fell into two groups: CT-naive (no prior-CT) and CT-pretreated (platinum-based CT followed by ICI on progression). The response rate (RR), progression-free survival (PFS), and duration of response (DOR) were assessed. A total of 29 patients received CT following progression on ICI. The median follow-up was 17.0mo (interquartile range 9.1-20.5mo). In the CT-naive group (n=17), 53% had a partial response, 18% had stable disease, and 29% had progressive disease. In the CT-pretreated group (n=12) 17% had a partial response, 67% had stable disease, and 16% had progressive disease. The median PFS was 6.4mo (95% confidence interval [CI] 3.8-9.1) in the CT-naive and 4.4mo (95% CI 1.5-7.3) in the CT-pretreated group. The median DOR was 8.1mo (range 5.1-11.1) among the ten patients with a response to CT after ICI in both groups. Some 38% of patients in the CT-naive and 17% in the CT-pretreated group had dose reductions on post-ICI CT. CT and ICI can be sequenced after previous chemotherapy exposure, although this does not induce long-term durable remissions in most patients. PATIENT SUMMARY: We looked at outcomes for patients with metastatic bladder cancer who received chemotherapy after the cancer got worse while on immunotherapy. We found that patients can be safely treated with further chemotherapy. However, the positive effects of chemotherapy will not be durable in the majority of patients.

Conformal Load-Bearing Antenna Structures-Mechanical Loading Considerations.

One of the important functions of antennas is to facilitate wireless communication. The IEEE 802.11 is part of the IEEE802 set of local area network technical standards, and specifies the media access control and physical layer protocols for implementing wireless local area network computer communication. The network physical layer protocol with a centre frequency of 2.4 GHz has a bandwidth of 22 MHz. A conformal load-bearing antenna structure (CLAS) facilitating this communication band that is tuned to 2.4 GHz must remain within this bandwidth. The aim of this paper is to investigate the effects of mechanical loading imposed on a load-bearing patch antenna with respect to its ability to remain within the specified bandwidth. The mechanical loading configurations considered include tensile, biaxial, and twisting. This paper will also report on the response of the antenna patch to the presence of a disbond between the metallised antenna and its substrate, which can arise due to fabrication anomalies and operational usage. This numerical work will assist in the design of experimental testing of the mechanical and electromagnetic properties of an embedded CLAS, which will ultimately be used to inform selection of appropriate regions to place patch antennas on load-bearing deformable surfaces.

Effectiveness and Reliability of Foot Orthoses on Impact Loading and Lower Limb Kinematics When Running at Preferred and Nonpreferred Speeds.

This study examined the effect of foot orthoses used on ground reaction forces, ankle, and knee kinematics when running at preferred and nonpreferred speeds. Sixteen runners ran on instrumented treadmills at various speeds (90%, 100%, and 110% of preferred speed) when wearing arch-support and flat-control orthoses. Two-way repeated analysis of variance (ANOVA) was performed on the mean and coefficient of variation of all variables. Results indicated that arch-support orthoses experienced larger maximum loading rates than flat-control orthoses (P = .017, 95% CI, 2.22 to 19.53). Slower speed was related to smaller loading rates (preferred: P = .002, 95% CI, -17.02 to -4.20; faster: P = .003, 95% CI, -29.78 to -6.17), shorter stride length (preferred: P < .001, 95% CI, -0.204 to -0.090; faster: P < .001, 95% CI, -0.382 to -0.237), and longer contact time (preferred: P < .001, 95% CI, 0.006-0.021; faster: 95% CI, 0.012-0.042). In arch-support condition, preferred speed induced higher stride length coefficient of variation (P = .046, 95% CI, 0.035-1.117) than faster speed, while displaying no differences in flat-control condition. These findings suggest that the use of arch-support orthoses would influence impact loading, but not spatial-temporal and joint kinematics in recreational runners.

Life-threatening polymyositis with spontaneous hematoma induced by nivolumab in a patient with previously resected melanoma.

Single-agent anti-PD1 antibodies are usually very well tolerated, but serious toxicity can still occur. Despite the PD-1 pathway seems to be relevant in the pathogenesis of immune-related myositis, anti-PD1-related myositis is generally a rare side effect of the treatment and usually not serious. However, its frequency is likely to increase as the use of immune checkpoint blockades. We present here a case of life-threatening polymyositis with associated spontaneous muscular hematoma in a patient treated with single-agent nivolumab in the adjuvant setting. Spontaneous hematoma is an extremely rare complication with unclear etiology of idiopathic myositis. Very few cases have been reported in the literature and their outcome has been often fatal. To our knowledge, this is the first case of autoimmune myositis and spontaneous heamatoma associated with the administration of single-agent checkpoint blockade. Anti-PD1 antibodies have changed the treatment landscape for a number of cancer entities in the past few years. When given as single agent they are usually very well tolerated, but serious rare toxicity can still occur. We present here a case of polymyositis with associated spontaneous muscular hematoma in a patient treated with single agent nivolumab.

Red cell differential width (RDW) as a predictor of survival outcomes with palliative and adjuvant chemotherapy for metastatic penile cancer.

PURPOSE: Red cell distribution width (RDW) measures red cells' size variability. Metastatic penile cancer displays poor chemotherapy response. As no validated prognostic predictor exists, we investigated whether RDW correlates independently with survival outcomes in metastatic penile cancer treated by chemotherapy. METHODS: Electronic chemotherapy files of patients with metastatic penile cancer (M1 or N3) from a large academic supra-regional centre were retrospectively analysed between 2005 and 2018. Patients were stratified into RDW > 13.9% and < 13.9%, as per published data on RDW in renal cell carcinoma. Survival time was calculated from the date of chemotherapy initiation until the date of death. RESULTS: 58 patients were analysed. The RDW-high group (n = 31) had a poorer survival than the RDW-low group (n = 27). Median overall survival (mOS) in all patients was 19.0 months (95% CI 13.1-24.9). mOS for RDW-high was 15.0 months (95% CI 10.1-19.9) and 37.0 months (95% CI 32.3-43.1) for RDW-low. Kaplan-Meier curves showed a clear disparity in survival (log rank p = 0.025). Cox proportional hazard ratio for death, corrected for T-stage, grade, age and deprivation score was 0.43 (p = 0.04). Sub-analysis of the M1 patients showed mOS in RDW-high of 17 m (95% CI 11.6-22.4) vs. NR; HR for death of 0.42. N3 patients' mOS in RDW-high cohort was 30 months (95% CI 4.5-55.9) vs. 13 months (95% CI 1.8-24.2) in RDW-low; HR for death was 0.30. CONCLUSION: RDW correlates independently with survival outcomes in metastatic penile cancer and may act as a potential predictor of survival outcomes for patients with metastatic penile cancer receiving chemotherapy.

Cytoreductive nephrectomy in metastatic renal cell carcinoma: outcome of patients treated with a multidisciplinary, algorithm-driven approach.

PURPOSE: Metastatic renal cell carcinoma (mRCC) represents a significant and rising burden of disease, with rapidly evolving treatment modalities. The role of cytoreductive nephrectomy (CN) is controversial in this setting. As such, London Cancer has pursued a multidisciplinary team (MDT) approach when assessing suitability for surgery. METHODS: A retrospective analysis of treatment-naive synchronous mRCC patients, managed via a renal-specialist MDT, was conducted between January 2015 and December 2018. An MDT selection algorithm for CN-using the International Metastatic Renal Cell Carcinoma Database Consortium score (IMDC), performance status and metastatic disease burden-was developed. RESULTS: 87 treatment-naive synchronous mRCC patients received either CN (n = 18), Systemic therapy (ST) alone (n = 43) or Best supportive care (BSC) (n = 26). Progression free survival (PFS) and overall survival (OS) were assessed. 51% and 39% were IMDC intermediate and poor risk. Median PFS was 28.6 months and 4.5 months in the CN group and ST alone group, respectively, Hazard Ratio for death was 3.63 [(95% CI 1.68-7.83) p < 0.05]. OS remains immature for the CN group, but a median OS of 12.8 months was observed in the ST group and 5.0 months for BSC. 1-year OS rate for CN, ST and BSC groups was 77.8%, 55.8% and 23.10%, respectively. CONCLUSION: These findings describe outcomes of an unselected series of patients treated via an MDT-driven, protocolised treatment pathway. MDT pathway-based decision making may improve patient selection for CN. Further research is needed to evaluate the role of CN amongst a growing landscape of treatment strategies, including immune checkpoint inhibitors and combination therapies. Multi-disciplinary team, pathway-based treatment strategy may improve patient selection for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma.

DirectPET: full-size neural network PET reconstruction from sinogram data.

Purpose: Neural network image reconstruction directly from measurement data is a relatively new field of research, which until now has been limited to producing small single-slice images (e.g., 1 × 128 × 128 ). We proposed a more efficient network design for positron emission tomography called DirectPET, which is capable of reconstructing multislice image volumes (i.e., 16 × 400 × 400 ) from sinograms. Approach: Large-scale direct neural network reconstruction is accomplished by addressing the associated memory space challenge through the introduction of a specially designed Radon inversion layer. Using patient data, we compare the proposed method to the benchmark ordered subsets expectation maximization (OSEM) algorithm using signal-to-noise ratio, bias, mean absolute error, and structural similarity measures. In addition, line profiles and full-width half-maximum measurements are provided for a sample of lesions. Results: DirectPET is shown capable of producing images that are quantitatively and qualitatively similar to the OSEM target images in a fraction of the time. We also report on an experiment where DirectPET is trained to map low-count raw data to normal count target images, demonstrating the method's ability to maintain image quality under a low-dose scenario. Conclusion: The ability of DirectPET to quickly reconstruct high-quality, multislice image volumes suggests potential clinical viability of the method. However, design parameters and performance boundaries need to be fully established before adoption can be considered.

A Role of Cholesterol in Modulating the Binding of α-Synuclein to Synaptic-Like Vesicles.

α-Synuclein (αS) is a presynaptic protein whose aggregation is associated with Parkinson's disease (PD). Although the physiological function of αS is still unclear, several lines of evidence indicate that this protein may play a role in the trafficking of synaptic vesicles (SVs) during neurotransmitter release, a task associated with its ability to bind SVs and promote their clustering. It is therefore crucial to identify the cellular factors that modulate this process. To address this question, using nuclear magnetic resonance (NMR) spectroscopy we have characterized the role of cholesterol, a major component of the membrane of SVs, in the binding of αS with synaptic-like vesicles. Our results indicate that cholesterol can act as a modulator of the overall affinity of αS for SVs by reducing the local affinity of the region spanning residues 65-97 in the non-amyloid-ß component (NAC) of the protein. The increased population of bound states that expose the region 65-97 to the solvent was found to induce stronger vesicle-vesicle interactions by αS. These results provide evidence that cholesterol modulates the clustering of synaptic vesicles induced by (α)S, and supports the role of the disorder-to-order equilibrium of the NAC region in the modulation of the biological properties of the membrane-bound state of αS.

International consensus definition of low anterior resection syndrome.

AIM: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. METHOD: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. RESULTS: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSION: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Fatigue Performance of Type I Fibre Bragg Grating Strain Sensors.

Although fibre Bragg gratings (FBGs) offer obvious potential for use in high-density, high-strain sensing applications, the adoption of this technology in the historically conservative aerospace industry has been slow. There are several contributing factors, one of which is variability in the reported performance of these sensors in harsh and fatigue prone environments. This paper reports on a comparative evaluation of the fatigue performance of FBG sensors written according to the same specifications using three different grating manufacturing processes: sensors written in stripped and re-coated fibres, sensors written during the fibre draw process and sensors written through fibre coating. Fatigue cycling of the fibres is provided by a customized electro-dynamically actuated loading assembly designed to provide high frequency and amplitude loading. Pre- and post-fatigue microscopic analysis and high-resolution transmission and reflection spectra scanning are conducted to investigate the fatigue performance of FBGs, the failure regions of fibres as well as any fatigue-related effects on the spectral profiles. It was found that because of the unique fabrication method, the sensors written through the fibre coating, also known as trans-jacket FBGs, show better fatigue performance than stripped and re-coated FBGs with greater control possible to tailor the optical reflection properties compared to gratings written in the draw tower. This emerging method for inscription of Type I gratings opens up the potential for mass production of higher reflectivity, apodised sensors with dense or complex array architectures which can be adopted as sensors for harsh environments such as in defence and aerospace industries.

Immediate-early gene Homer1a intranuclear transcription focus intensity as a measure of relative neural activation.

Immediate-early genes (IEGs) exhibit a rapid, transient transcription response to neuronal activation. Fluorescently labeled mRNA transcripts appear as bright intranuclear transcription foci (INF), which have been used as an all-or-nothing indicator of recent neuronal activity; however, it would be useful to know whether INF fluorescence can be used effectively to assess relative activations within a neural population. We quantified the Homer1a (H1a) response of hippocampal neurons to systematically varied numbers of exposures to the same places by inducing male Long-Evans rats to run laps around a track. Previous studies reveal relatively stable firing rates across laps on a familiar track. A strong linear trend (r2 > 0.9) in INF intensity was observed between 1 and 25 laps, after which INF intensity declined as a consequence of dispersion related to the greater elapsed time. When the integrated fluorescence of the entire nucleus was considered instead, the linear relationship extended to 50 laps. However, there was only an approximate doubling of H1a detected for this 50-fold variation in total spiking. Thus, the intranuclear H1a RNA fluorescent signal does provide a relative measure of how many times a set of neurons was activated over a ~10 min period, but the dynamic range and hence signal-to-noise ratios are poor. This low dynamic range may reflect previously reported reductions in the IEG response during repeated episodes of behavior over longer time scales. It remains to be determined how well the H1a signal reflects relative firing rates within a population of neurons in response to a single, discrete behavioral event.