Prostate Cancer Detection with a Tactile Resonance Sensor-Measurement Considerations and Clinical Setup.

Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (p < 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.

A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy- first investigations of single biological cells.

The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.

Point-of-care diagnostics for infection and antimicrobial resistance in sub-Saharan Africa: A narrative review.

OBJECTIVES: Sub-Saharan African (SSA) countries are severely impacted by antimicrobial resistance (AMR). Due to gaps in access to diagnostics in SSA, the true extent of AMR remains unknown. This diagnostic gap affects patient management and leads to significant antimicrobial overuse. This review explores how point-of-care (POC) testing for pathogen identification and AMR may be used to close the diagnostic gap in SSA countries. METHODS: A narrative review exploring current clinical practice and novel developments in the field of POC testing for infectious diseases and AMR. RESULTS: POC assays for identification of various pathogens have been successfully rolled out in SSA countries. While implementation studies have mostly highlighted impressive test performance of POC assays, there is limited data on the impact of implementation on clinical outcomes and cost-effectiveness. We did not encounter local studies of host-directed POC assays relevant to AMR. Novel POC assays using real-time polymerase chain reaction, isothermal amplification, microfluidics, and other technologies are in various stages of development. CONCLUSIONS: Available literature shows that POC testing for AMR applications is implementable in SSA and holds the potential to reduce the diagnostic gap. Implementation will require effective regulatory pathways, incorporation of POC testing in clinical and laboratory guidelines, and adequate value capture in existing health financing models.

Optical fibre probe NIR Raman measurements in ambient light and in combination with a tactile resonance sensor for possible cancer detection.

First measurements on a combined instrument with a thin fibre optic Raman probe mounted inside a hollow tactile resonance sensor have been performed in ambient light on porcine tissue. The ambient fluorescent light was removed successfully from the spectra. The stiffness and the biomolecular composition of the tissue were analysed.

Study protocol for a randomized, controlled, multicentre, pragmatic trial with Rehabkompassen®-a digital structured follow-up tool for facilitating patient-tailored rehabilitation in persons after stroke.

BACKGROUND: Stroke is a leading cause of disability among adults worldwide. A timely structured follow-up tool to identify patients' rehabilitation needs and develop patient-tailored rehabilitation regimens to decrease disability is largely lacking in current stroke care. The overall purpose of this study is to evaluate the effectiveness of a novel digital follow-up tool, Rehabkompassen®, among persons discharged from acute care settings after a stroke. METHODS: This multicentre, parallel, open-label, two-arm pragmatic randomized controlled trial with an allocation ratio of 1:1 will be conducted in Sweden. A total of 1106 adult stroke patients will have follow-up visits in usual care settings at 3 and 12 months after stroke onset. At the 3-month follow-up, participants will have a usual outpatient visit without (control group, n = 553) or with (intervention group, n = 553) the Rehabkompassen® tool. All participants will receive the intervention at the 12-month follow-up visit. Feedback from the end-users (patient and health care practitioners) will be collected after the visits. The primary outcomes will be the patients' independence and social participation at the 12-month visits. Secondary outcomes will include end-users' satisfaction, barriers and facilitators for adopting the instrument, other stroke impacts, health-related quality of life and the cost-effectiveness of the instrument, calculated by incremental cost per quality-adjusted life year (QALY). DISCUSSION: The outcomes of this trial will inform clinical practice and health care policy on the role of the Rehabkompassen® digital follow-up tool in the post-acute continuum of care after stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915027. Registered on 4 June 2021. ISRCTN registry ISRCTN63166587. Registered on 21 August 2023.

Assessments of a novel digital follow-up tool Rehabkompassen® to identify rehabilitation needs among stroke patients in an outpatient setting.

Introduction: It remains a huge challenge to identify individual rehabilitation needs in a time-efficient manner for providing patient-tailored rehabilitation during the continuum of stroke care. We have recently demonstrated the usefulness of a paper-version Rehab-Compass as a follow-up tool. The aim of the current study was to develop a digital version of the Rehab-Compass and evaluate its usability and feasibility. Methods: The novel digital tool Rehabkompassen® was developed by an iterative and participatory design process. Patients' rehabilitation needs were visualized by the tool and used before, during, and after the consultation. The usability and feasibility of the tool was assessed by task completion rate, the System Usability Scale, and satisfaction questionnaires among 2 physicians and 24 adult stroke patients in an outpatient clinical setting. Results: Rehabkompassen® identified and graphically visualized a panoramic view of the stroke patients' multidimensional needs in individual- and group levels. The instrument appeared to be feasible and time efficient in clinical use with a 100% overall task completion rate for both patients and physicians. A majority of the patients reported that it was very easy or fairly easy to answer the digital questionnaires and to understand their own digital Rehab-Compass graph. Two physicians reported a high mean score on the System Usability Scale (95/100) and were positive about using the tool in the future. Conclusions: The current results indicated that Rehabkompassen® was a feasible, useful, and time-saving follow-up tool for the identification of rehabilitation needs among stroke survivors in the post-acute continuum of care after stroke. Further research is needed to evaluate the efficacy of the digital instrument among stroke patients.

Digital Graphic Follow-up Tool (Rehabkompassen) for Identifying Rehabilitation Needs Among People After Stroke: Randomized Clinical Feasibility Study.

BACKGROUND: Stroke is a leading cause of disability among adults, with heavy social and economic burden worldwide. A cost-effective solution is urgently needed to facilitate the identification of individual rehabilitation needs and thereby provide tailored rehabilitations to reduce disability among people who have had a stroke. A novel digital graphic follow-up tool Rehabkompassen has recently been developed to facilitate capturing the multidimensional rehabilitation needs of people who have had a stroke. OBJECTIVE: The aim of this study was to evaluate the feasibility and acceptability of conducting a definitive trial to evaluate Rehabkompassen as a digital follow-up tool among people who have had a stroke in outpatient clinical settings. METHODS: This pilot study of Rehabkompassen was a parallel, open-label, 2-arm prospective, proof-of-concept randomized controlled trial (RCT) with an allocation ratio of 1:1 in a single outpatient clinic. Patients who have had a stroke within the 3 previous months, aged ≥18 years, and living in the community were included. The trial compared usual outpatient visits with Rehabkompassen (intervention group) and without Rehabkompassen (control group) at the 3-month follow-up as well as usual outpatient visit with Rehabkompassen at the 12-month follow-up. Information on the recruitment rate, delivery, and uptake of Rehabkompassen; assessment and outcome measures completion rates; the frequency of withdrawals; the loss of follow-up; and satisfaction scores were obtained. The key outcomes were evaluated in both groups. RESULTS: In total, 28 patients (14 control, 14 Rehabkompassen) participated in this study, with 100 patients screened. The overall recruitment rate was 28% (28/100). Retention in the trial was 86% (24/28) at the 12-month follow-up. All participants used the tool as planned during their follow-ups, which provided a 100% (24/24) task completion rate of using Rehabkompassen and suggested excellent feasibility. Both patient- and physician-participants reported satisfaction with the instrument (19/24, 79% and 2/2, 100%, respectively). In all, 2 (N=2, 100%) physicians and 18 (N=24, 75%) patients were willing to use the tool in the future. Furthermore, modified Rankin Scale as the primary outcome and various stroke impacts as secondary outcomes were both successfully collected and compared in this study. CONCLUSIONS: This study demonstrated the high feasibility and adherence of the study protocol as well as the high acceptability of Rehabkompassen among patients who have had a stroke and physicians in an outpatient setting in comparison to the predefined criterion. The information collected in this feasibility study combined with the amendments of the study protocol may improve the future definitive RCT. The results of this trial support the feasibility and acceptability of conducting a large definitive RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915027; https://clinicaltrials.gov/ct2/show/NCT04915027.

Market concentration of new antibiotic sales.

We calculate the average sales of new antibiotics during their first 8 years on the market. The discounted net present value is only $240 m in total per antibiotic, well below costs of supplying these products. The reliance on the US for sales is striking: the US market accounts for 84% of sales during the first 8 years. These facts clarify the need for additional revenues, especially from other countries, to support incentives for the development of new antibiotics. Market entry rewards may be of particular value.

A tactile resonance sensor for prostate cancer detection - evaluation on human prostate tissue.

Prostate cancer surgery risks erectile problems and incontinence for the patient. An instrument for guiding surgeons to avoid nerve bundle damage and ensure complete cancer removal is desirable. We present a tactile resonance sensor made of PZT ceramics, mounted in a 3D motorized translation stage for scanning and measuring tissue stiffness for detecting cancer in human prostate. The sensor may be used during surgery for guidance, scanning the prostate surface for the presence of cancer, indicating migration of cancer cells into surrounding tissue. Ten fresh prostates, obtained from patients undergoing prostate cancer surgery, were cut into 0.5 cm thick slices. Each slice was measured for tissue stiffness at about 25 different sites and compared to histology for validation cancer prediction by stiffness. The statistical analysis was based on a total of 148 sites with non-cancer and 40 sites with cancer. Using a generalized linear mixed model (GLMM), the stiffness data predicted cancer with an area under the curve of 0.74, after correcting for overfitting using bootstrap validation. Mean prostate stiffness on the logarithmic scale (p = 0.015) and standardized Z-scores (p = 0.025) were both significant predictors of cancer. This study concludes that stiffness measured by the tactile resonance sensor is a significant predictor of prostate cancer with potential for future development towards a clinical instrument for surgical guidance.

Industry incentives and antibiotic resistance: an introduction to the antibiotic susceptibility bonus.

The scarcity of novel antibiotic compounds in a time of increasing resistance rates has begun to ring alarm bells at the highest echelons of government. Large new financial incentives to accelerate antibiotic research and development, such as market entry rewards (MERs), are being considered. However, there is little focus on how to sustain the efficacy of new, promising antibiotics reaching the market. Currently, inappropriate use of antibiotics is commonplace, which has accelerated resistance development. In an attempt to halt this trend, antibiotic stewardship policies are being implemented in many resource-rich settings. Unfortunately, this has not yet had an impact on the amount of antibiotics being prescribed globally. One important hurdle is misalignment of incentives. While governments and health services are incentivized to promote prudent use of this common good, pharmaceutical companies are incentivized to increase volume of sales to maximize profits. This problem must be addressed or else the major efforts going into developing new antibiotics will be in vain. In this paper we outline an approach to realign the incentives of pharmaceutical companies with wider antibiotic conservation efforts by making a staged bonus a component of an MER for antibiotic developers when resistance to their drug remains low over time. This bonus could address the lack of stewardship focus in any innovation-geared incentive.

Effects of snap-freezing and near-infrared laser illumination on porcine prostate tissue as measured by Raman spectroscopy.

Most Raman spectroscopic studies on tissue are performed in vitro. To assure that the results are applicable to in vivo examinations, preparation protocols and measurement procedures of tissue for in vitro studies should preserve tissue characteristics close to the native state. This study had two aims. The first was to elucidate if photoinduced effects arise during 5 minutes' continuous illumination of tissue with an 830 nm laser at an irradiance of approximately 3 x 10(10) W/m2. The second was to investigate the effects of snap-freezing of porcine prostate tissue in liquid nitrogen and subsequent storage at -80 degrees C, by means of multivariate analysis. 830 nm laser illumination of the specified irradiance did not affect the Raman spectra. A decrease of the spectral background was observed, likely due to photobleaching of tissue fluorophores. Snap-freezing and subsequent storage at -80 degrees C gave rise to subtle but significant alterations in Raman spectra, most likely related to changes in the protein conformations.

Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1)F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Antibiotic Pipeline Coordinators.

The World Health Organization (WHO) has published a global priority list of antibiotic-resistant bacteria to guide research and development (R&D) of new antibiotics. Every pathogen on this list requires R&D activity, but some are more attractive for private sector investments, as evidenced by the current antibacterial pipeline. A "pipeline coordinator" is a governmental/non-profit organization that closely tracks the antibacterial pipeline and actively supports R&D across all priority pathogens employing new financing tools.

Simulating Market Entry Rewards for Antibiotics Development.

We design an agent based Monte Carlo model of antibiotics research and development (R&D) to explore the effects of the policy intervention known as Market Entry Reward (MER) on the likelihood that an antibiotic entering pre-clinical development reaches the market. By means of sensitivity analysis we explore the interaction between the MER and four key parameters: projected net revenues, R&D costs, venture capitalists discount rates, and large pharmaceutical organizations' financial thresholds. We show that improving revenues may be more efficient than reducing costs, and thus confirm that this pull-based policy intervention effectively stimulates antibiotics R&D.

Spatial variations in prostate tissue histology as measured by a tactile resonance sensor.

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensor's stiffness-measuring properties can reflect tissue pathology. The change in the frequency of the resonating system and the change in force when contact is made with tissue are used as a stiffness parameter. Earlier stiffness measurements of prostate tissue in vitro demonstrate variations related to tissue composition. In this study, measured stiffness from two human prostate specimens was compared to histological composition of prostate tissue below and around the measurement points. Tissue stiffness was measured with the resonance sensor system. Tissue composition was measured at four different depths in the tissue specimen using a microscopic-image-based morphometrical method. With this method, the proportion of tissue types was determined at the points of intersections in a circular grid on the images representing each measurement point. Numerical values were used for weighting the tissue proportions at different depths in the tissue specimen. For an impression depth of 1.0 mm, the sensing depth in this study was estimated to be 3.5-5.5 mm. Stiffness variations due to horizontal tissue variations were investigated by studying the dependence of the size of the circular grid area relative to the contact area of the sensor tip. The sensing area (grid radius) was estimated to be larger than the contact area (contact radius) between the sensor tip and the tissue. Thus, the sensor tip registers spatial variations in prostate tissue histology, both directly below and lateral to the tip itself. These findings indicate that tumours around the sensor tip could be detected, which in turn supports the idea of a future resonance-sensor-based clinical device for detecting tumours and for guiding biopsies.

Sensitivity improvements of a resonance-based tactile sensor.

Resonance-based contact-impedance measurement refers to the application of resonance sensors based on the measurement of the changes in the resonance curve of an ultrasonic resonator in contact with a surface. The advantage of the resonance sensor is that it is very sensitive to small changes in the contact impedance. A sensitive micro tactile sensor (MTS) was developed, which measured the elasticity of soft living tissues at the single-cell level. In the present paper, we studied the method of improving the touch and stiffness sensitivity of the MTS. First, the dependence of touch sensitivity in relation to the resonator length was studied by calculating the sensitivity coefficient at each length ranging from 9 to 40 mm. The highest touch sensitivity was obtained with a 30-mm-long glass needle driven at a resonance frequency of 100 kHz. Next, the numerical calculation of contact impedance showed that the highest stiffness sensitivity was achieved when the driving frequency was 100 kHz and the contact-tip diameter of the MTS was 10 µm. The theoretical model was then confirmed experimentally using a phase-locked-loop-based digital feedback oscillation circuit. It was found that the developed MTS, whose resonant frequency was 97.030 kHz, performed with the highest sensitivity of 53.2 × 106 Hz/N at the driving frequency of 97.986 kHz, i.e. the highest sensitivity was achieved at 956 Hz above the resonant frequency.

Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

Prostate cancer detection with an improved resonance sensor system: parameter evaluation in a silicone model and on human prostate tissue in vitro.

The purpose of this study was to improve a resonance sensor system for prostate cancer detection and evaluate its performance on silicone with different hardness. Furthermore, to investigate if the instrument could distinguish between cancerous and normal prostate tissue in one in vitro prostate specimen. The system could measure the frequency shift, impression depth and the rise time of the force signal. The frequency shift, impression depth and the rise time described the relative hardness of silicone (n = 50, P < 0.05). The results from measurements on the prostate specimen indicated that there is a significant difference in the parameter data between cancerous and normal prostate tissue (n = 15, P < 0.05). The parameters' impression depth and force rise time adds important information for cancer detection. Further studies on prostate tissue with different tumour types must be performed in order to understand the full value of the new sensor system.

Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

Underestimation of intraocular pressure after photorefractive keratectomy: a biomechanical analysis.

Excimer laser surgery, to correct corneal refraction, induces changes in corneal thickness and curvature. Both factors can cause measurement errors when determining intraocular pressure (IOP). This study evaluates effects of photorefractive keratectomy (PRK) on IOP measurements, using Goldmann applanation tonometry (GAT) and Applanation resonance tonometry (ART), in an in vitro model. Six porcine eyes was enucleated and pressurised to a constant IOP=30 mmHg. After removal of the epithelium, the eyes were PRK-treated for a total of 25 dioptres. The measured IOP decreased 13.2 mmHg for GAT and 9.0 mmHg for ART. The total underestimation by GAT was larger than for ART, and a part of the ART underestimation (3.5 mmHg) was assigned to sensitivity to the change in corneal surface structure resulting from the removal of epithelium. The flat contact probe of GAT, as compared with the convex tip of ART, provided explanation for the difference in IOP measurement error after PRK.