ICARUS at the Fermilab Short-Baseline Neutrino program: initial operation.

The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous νe appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV2. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

The Patient Beyond the Sphincter-Cognitive and Functional Considerations Affecting the Natural History of Artificial Urinary Sphincters.

Artificial urinary sphincters (AUS) are common. Life expectancy at average implantation (71.5 years) is 14 years. During this period patients must still possess manual dexterity and cognitive capabilities needed to operate the AUS, otherwise it is practically unfunctional. Still, available data regarding AUS durability deal with medical and mechanical factors. Issues as age-related deteriorating manual dexterity and cognitive capabilities precluding patients from operating an apparently intact AUS have not been addressed. We set to focus on these aspects. We review the natural history of manual dexterity, physical, and cognitive deterioration of aging men and propose counseling and screening algorithms for evaluating these aspects.

Functional characterization of two new STAT3 mutations associated with hyper-IgE syndrome in a Mexican cohort.

Hyper-IgE syndrome (HIES) is an immunodeficiency disorder that is characterized by distinctive immunologic and non-immunologic manifestations. Although mutations in signal transducer and activator of transcription 3 (STAT3) have been associated with HIES, the exact nature of the relationship is unknown. Here, we characterized the functional activity of STAT3 and its mutations in 11 Mexican patients with autosomal dominant HIES. STAT3 phosphorylation was evaluated by flow cytometry, and in silico analyses were performed to estimate the impact of allelic mutations on the DNA binding and SH2 domains of the STAT3 protein. Electrophoretic mobility shift assays were used to assess whether the STAT3 mutants could bind to the consensus oligonucleotide target in vitro. Two novel mutations [g.58891A>T (Asn395Tyr) and g.59078A>T (Asn425Tyr)] as well as one possible somatic mosaicism were found in several of the patients who bore some remarkable features. However, there were no direct correlations between genotypes and HIES clinical features. STAT3 phosphorylation was found to be lower in the patient cohort than in healthy controls. Moreover, the mutated STAT3 proteins could bind to the Sp1, but not to the STAT3, consensus sequence. From these functional studies, the STAT3 mutations found in our patient cohort were concluded to be deleterious for normal STAT3 function.

Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay

BACKGROUND: There are two inheritance patterns, the X-linked recessive (XL) pattern and the autosomal recessive pattern. There is no information on the predominant inheritance pattern of male patients with chronic granulomatous disease (CGD) in Mexico. OBJECTIVE: The aim of this study was to determine the inheritance pattern in a cohort of Mexican male patients with CGD by means of the detection of an XL status carrier among their female relatives, and to describe the frequency of discoid lupus (DL) among carriers. METHODS: We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. All carriers were questioned for current or past established DL diagnosis. RESULTS: We detected 33 families with one or more CGD male patients; we found an XL-CGD in 79% of the relatives from at least one female relative with a bimodal pattern. For the remaining seven relatives we were not able to confirm a carrier status by means of a DHR assay. Moreover, we detected one mother with CGD secondary to skewed X-chromosome inactivation. We also found 47 carriers, and only one carrier with DL among them. CONCLUSION: We concluded that XL-CGD is the most frequent form of CGD in a cohort of CGD male patients in Mexico. DHR assay is a fast and practical tool to determine the CGD form in the Latin-American countries. Finally, DL frequency in Mexico is lower than that reported in the literature for other regions of the world

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Detection of inheritance pattern in thirty-three Mexican males with chronic granulomatous disease through 123 dihydrorhodamine assay.

BACKGROUND: There are two inheritance patterns, the X-linked recessive (XL) pattern and the autosomal recessive pattern. There is no information on the predominant inheritance pattern of male patients with chronic granulomatous disease (CGD) in Mexico. OBJECTIVE: The aim of this study was to determine the inheritance pattern in a cohort of Mexican male patients with CGD by means of the detection of an XL status carrier among their female relatives, and to describe the frequency of discoid lupus (DL) among carriers. METHODS: We detected the female relatives within the families of male patients with CGD, and carried out the 123 dihydrorhodamine (DHR) assay in all female participants. All carriers were questioned for current or past established DL diagnosis. RESULTS: We detected 33 families with one or more CGD male patients; we found an XL-CGD in 79% of the relatives from at least one female relative with a bimodal pattern. For the remaining seven relatives we were not able to confirm a carrier status by means of a DHR assay. Moreover, we detected one mother with CGD secondary to skewed X-chromosome inactivation. We also found 47 carriers, and only one carrier with DL among them. CONCLUSION: We concluded that XL-CGD is the most frequent form of CGD in a cohort of CGD male patients in Mexico. DHR assay is a fast and practical tool to determine the CGD form in the Latin-American countries. Finally, DL frequency in Mexico is lower than that reported in the literature for other regions of the world.

Clinical and immunological features of common variable immunodeficiency in Mexican patients

BACKGROUND: Common variable immunodeficiency (CVID) is characterised by hypogammaglobulinaemia and a broad clinical spectrum, mainly showing recurrent bacterial infections accompanied sometimes by increased susceptibility to chronic lung disease, autoimmunity, and neoplastic diseases. OBJECTIVES: To evaluate the clinical and immunological characteristics of patients with CVID in Mexico. METHODS: This is a retrospective analysis of 43 patients with CVID from the Immunology Division of seven different reference centres in Mexico. Patients were diagnosed according to the diagnostic criteria of the European Society for Immunodeficiency Diseases. We collected demographics, clinical and immunological data from each patient and a statistical analysis was performed. RESULTS: There were 23 (53.5%) male and 20 (46.5%) female patients. Median age at onset of disease was 13.7 years, and median age at diagnosis was 19 years. Average delay in diagnosis was 12.5 years. The median total serum levels of IgG, IgM, and IgA at diagnosis were 175, 18, and 17.8 mg/dL, respectively. The mean percentage of CD19+ B cells was 8.15%. Sinusitis (83%), pneumonia (83%), gastrointestinal infection (70%), and acute otitis media (49%) were the most common manifestations. Bronchiectasis was present in 51% of the patients, 44% manifested non-infectious chronic diarrhoea, and 70% experienced weight loss. Autoimmunity was present in 23% of the patients; haemolytic anaemia and autoimmune thrombocytopenic purpura were the most common presentations. Allergy was present in 30.2% of patients, with allergic rhinitis and asthma being the most frequent types. Two patients developed malignancy. All the patients received Intravenous immunoglobulin (IVIG) as a fundamental part of the treatment at a mean dose of 408 mg/kg. CONCLUSION: This is the first cohort of CVID reported in Mexico We found that infection diseases were the most frequent presentations at onset. Moreover, patients had an average diagnosis delay of twelve years and thus a major prevalence of bronchiectasis. We suggest performing an extended analysis of patients with CVID patients in other Latin American countries

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Clinical and immunological features of common variable immunodeficiency in Mexican patients.

BACKGROUND: Common variable immunodeficiency (CVID) is characterised by hypogammaglobulinaemia and a broad clinical spectrum, mainly showing recurrent bacterial infections accompanied sometimes by increased susceptibility to chronic lung disease, autoimmunity, and neoplastic diseases. OBJECTIVES: To evaluate the clinical and immunological characteristics of patients with CVID in Mexico. METHODS: This is a retrospective analysis of 43 patients with CVID from the Immunology Division of seven different reference centres in Mexico. Patients were diagnosed according to the diagnostic criteria of the European Society for Immunodeficiency Diseases. We collected demographics, clinical and immunological data from each patient and a statistical analysis was performed. RESULTS: There were 23 (53.5%) male and 20 (46.5%) female patients. Median age at onset of disease was 13.7 years, and median age at diagnosis was 19 years. Average delay in diagnosis was 12.5 years. The median total serum levels of IgG, IgM, and IgA at diagnosis were 175, 18, and 17.8mg/dL, respectively. The mean percentage of CD19+ B cells was 8.15%. Sinusitis (83%), pneumonia (83%), gastrointestinal infection (70%), and acute otitis media (49%) were the most common manifestations. Bronchiectasis was present in 51% of the patients, 44% manifested non-infectious chronic diarrhoea, and 70% experienced weight loss. Autoimmunity was present in 23% of the patients; haemolytic anaemia and autoimmune thrombocytopenic purpura were the most common presentations. Allergy was present in 30.2% of patients, with allergic rhinitis and asthma being the most frequent types. Two patients developed malignancy. All the patients received Intravenous immunoglobulin (IVIG) as a fundamental part of the treatment at a mean dose of 408mg/kg. CONCLUSION: This is the first cohort of CVID reported in Mexico We found that infection diseases were the most frequent presentations at onset. Moreover, patients had an average diagnosis delay of twelve years and thus a major prevalence of bronchiectasis. We suggest performing an extended analysis of patients with CVID patients in other Latin American countries.

[Role of the community pharmacist in the management of drug related problems in home care patients]. / Rôle du pharmacien d'officine dans la gestion des problèmes liès aux médicaments dans le cadre des soins à domicile.

Medication management in home care is an error prone process. In a small pilot project in Flanders, community pharmacists collaborated with physicians and home care nurses through a shared electronic care plan, to optimize the medication management of their home care patients. The pilot project shows that GPs and nurses are positive about the possible contribution of the pharmacist in medication management of home care patients. A larger follow up study is necessary to further identify possible roles of pharmacists in home care and to show related health benefits.

Near-surface nanoscale InAs Hall cross sensitivity to localized magnetic and electric fields.

We have measured the room temperature response of nanoscale semiconductor Hall crosses to local applied magnetic fields under various local electric gate conditions using scanning probe microscopy. Near-surface quantum wells of AlSb/InAs/AlSb, located just 5 nm from the heterostructure surface, allow very high sensitivity to localized electric and magnetic fields applied near the device surfaces. The Hall crosses have critical dimensions of 400 and 100 nm, while the mean free path of the carriers is about 160 nm; hence the devices nominally span the transition from diffusive to quasi-ballistic transport. With certain small gate voltages (V(g)) the devices of both sizes are strongly responsive to the local magnetic field at the center of the cross, and the results are well described using finite element modeling. At high V(g), the response to local magnetic fields is greatly distorted by strong electric fields applied near the cross corners. However we observe no change in behavior with the size of the device.

Clinical validation of the "in silico" prediction of immunogenicity of a human recombinant therapeutic protein.

Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted promiscuous T-cell epitope(s) within the 14-amino-acid carboxy-terminal region of the peptide portion of FPX. On administration of FPX in 76 healthy human subjects, 37% developed antibodies after a single injection. A memory T-cell response against the above carboxy-terminus of the peptide was observed in antibody-positive but not in antibody-negative subjects. Promiscuity of the predicted T-cell epitope(s) was confirmed by representation of all common HLA alleles in antibody-positive subjects. As predicted by EpiMatrix, HLA haplotype DRB1*0701/1501 was associated with the highest T-cell and antibody response. In conclusion, in silico prediction can be successfully used to identify Class II restricted T-cell epitopes within therapeutic proteins and predict immunogenicity thereof in humans.

Effect of blood donation on maximal oxygen consumption.

AIM: This study determined the effect of donating one unit of blood on various physiological parameters associated with a VO2(max) test. METHODS: Ten healthy, male subjects (23+/-4 years, 178+/-7.6 cm, 74.4+/-12.3 kg) completed a VO2(max) test 24 h before donating one unit of blood (~500 mL) and 24 h after donating blood. The Bruce protocol was used to determine the subjects' VO2(max). Physiological responses were measured at the end of the VO2(max) test. A repeated measures ANOVA was used to determine if there were significant (P<0.05) differences in the subjects' physiological responses between the VO2(max) before and after blood donation. RESULTS: Significant differences were found in VO2(max) (mean+/-SD, 3.18+/-0.74 vs 2.87+/-0.53 L.min(-1)), cardiac output (Q, 25+/-5 vs 22.5+/-3.3 L.min(-1)), stroke volume (SV, 134+/-37 vs 121+/-22 mL.beat(-1)), delivery of oxygen (DO(2), 5+/-.87 vs 3.97+/-.68 L.min(-1)), and hemoglobin concentration (Hb, 153+/-12 vs 135+/-16 gm.L(-1)). No significant changes were observed for heart rate (HR); arteriovenous oxygen difference (a-vO(2) diff), systolic blood pressure (SBP), and diastolic blood pressure (DBP). CONCLUSIONS: These findings indicate that donating one unit of blood decreased VO2(max) due to the decrease in Q, which resulted from the decrease in SV since HR was unchanged. The lower VO2(max) along with the decrease in DO(2) would be expected to have a negative effect on athletic performance.

Role for calbindin-D28K in in vitro classical conditioning of abducens nerve responses in turtles.

Intracellular calcium has a pivotal role in synaptic modifications that may underlie learning and memory. The present study examined whether there were changes in immunoreactivity levels of the AMPA receptor subunits GluR2/3 and calcium binding proteins during classical conditioning recorded in the abducens nerve of in vitro brain stem preparations from turtles. The results showed that abducens motor neurons in unconditioned turtle brain stems were immunopositive for GluR2/3, calbindin-D28K, and calmodulin, but were immunonegative for parvalbumin. After classical conditioning, immunoreactivity for calbindin-D28K in the abducens motor nuclei was significantly reduced, whereas there were no significant changes in GluR2/3, calmodulin, or parvalbumin. This reduction in calbindin-D28K immunoreactivity was not observed following conditioning in the NMDA receptor antagonist AP-5, which blocked conditioned responses, suggesting that these changes are NMDA receptor-dependent. Moreover, the degree of the decrease in calbindin-D28K immunoreactivity was negatively correlated with the level of conditioning. Consistent with the immunocytochemical findings, Western blot analysis showed that calbindin-D28K protein levels were reduced after classical conditioning. The results support the hypothesis that in vitro classical conditioning of abducens nerve responses utilizes intracellular calcium-dependent signaling pathways that require NMDA receptor function and suggest a specific role for the calcium binding protein calbindin-D28K.

Detection and quantification of cocaine metabolites in urine samples from horses administered cocaine.

Cocaine is a naturally occurring alkaloid that is commonly abused by human-beings for its psychostimulatory effects. Occasionally, very small concentrations (i.e. <100 ng/mL) of the primary cocaine metabolite, benzoylecgonine (BZE) have been detected in urine collected from horses competing in athletic events. In this study urine samples, collected from four horses following the administration of 2.5 and 20 mg of cocaine sublingually and 50 mg of cocaine intravenously, were analyzed for the presence of cocaine and/or its metabolites by enzyme-linked immunosorbent assay (ELISA) and gas chromatography-mass spectrometry (GC-MS). The results of ELISA analysis of urine samples collected from all four horses suggested the presence of cocaine and/or its metabolites up to 10, 48, and 72 h after administration of 2.5, 20, and 50 mg of cocaine, respectively. The results of GC-MS analysis confirmed the presence of BZE above the limit of quantification (LOQ = 5 ng/mL) in urine samples collected from all four horses for up to 24 h after administration of 2.5 mg of cocaine and for up to 48 h after administration of 20 and 50 mg of cocaine. No obvious behavioral effects or overt alterations of heart rate or rhythm were noted in any of these horses after cocaine administration.

Application of disposable plastic microfluidic device arrays with customized chemistries to multiplexed biochemical assays.

Plastic microfluidic array platforms and synergistic multiplexed assay chemistries are under development for a variety of applications, including assays of gene expression, proteomics, genotyping, DNA sequencing and fragment analysis, sample preparation and high-throughput pharmaceutical discovery. The low production costs of plastic substrates makes possible economical single-use device arrays, eliminating cleaning and sample-to-sample carryover contamination. Hundreds of microchannels and reservoirs are readily included on a single microtitre-plate-size substrate, enabling the manufacture of highly parallel fluidic array systems to increase throughput and speed.

IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice.

IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform a was produced as fusion construct with human IgG1 Fc and assessed for binding and neutralizing IL-18. IL-18BP-Fc binds human, mouse, and rat IL-18 with high affinity (K(D) 0.3-5 nM) in a BIAcore-based assay. In vitro, IL-18BP-Fc blocks IL-18 (100 ng/ml)-induced IFN-gamma production by KG1 cells (EC(50) = 0.3 microg/ml). In mice challenged with an LD(90) of LPS (15 mg/kg), IL-18BP-Fc (5 mg/kg) administered 10 min before LPS blocks IFN-gamma production and protects against lethality. IL-18BP-Fc administered 10 min before LPS blocks IFN-gamma production induced by LPS (5 mg/kg) with ED(50) of 0.005 mg/kg. Furthermore, IL-18BP-Fc (5 mg/kg) abrogates LPS (5 mg/kg)-induced IFN-gamma production even when administered 6 days before LPS but shows no effect when administered 9 or 12 days before LPS. Given 10 min before LPS challenge to mice primed 12 days in advance with heat-killed Propionibacterium acnes, IL-18BP-Fc prevents LPS-induced liver damage and IFN-gamma and Fas ligand expression. Given at the moment of priming with P. acnes, IL-18BP-Fc decreases P. acnes-induced granuloma formation, macrophage-inflammatory protein-1alpha and macrophage-inflammatory protein-2 production and prevents sensitization to LPS. IL-18BP-Fc also prevents Con A-induced liver damage and IFN-gamma and Fas ligand expression as well as liver damage induced by Pseudomonas aeruginosa exotoxin A or by anti-Fas agonistic Ab. In conclusion, IL-18BP can be engineered and produced in recombinant form to generate an IL-18 inhibitor, IL-18BP-Fc, endowed with remarkable in vitro and in vivo properties of binding and neutralizing IL-18.

Metabolic cost of walking with and without a shoe lift on the contralateral foot of an immobilised extended knee.

The purpose of the present study was to determine the metabolic cost of walking with and without a shoe-lift on the contralateral foot of an immobilised extended knee. Eight male subjects were randomly allocated and participated in both the treatment (walking with a 2.5 cm shoe-lift) and control (walking without a shoe-lift) conditions. Cardiac output (Q) and related cardiovascular measurements were analysed to determine the effect of a shoe-lift on central (heart rate (HR); stroke volume (SV)) and peripheral (arteriovenous oxygen difference (a-vO2 diff)) components of oxygen consumption (VO2). A metabolic analyser was used to determine VO2 (ml x kg(-1) x min(-1)), which was converted to oxygen cost (ml x kg(-1) x m(-1)). The shoe-lift had no significant (p > 0.05) effect on VO2 or oxygen cost. There were no significant differences in Q, HR, SV, a-vO2 diff, systemic vascular resistance, carbon dioxide production, respiratory exchange ratio, expired ventilation, tidal volume and respiratory rate between the two walking conditions with and without a shoe-lift. These findings demonstrate that a shoe-lift added to the contralateral foot of an immobilised extended knee does not produce clinically important effects on oxygen cost or efficiency during walking.

Does nocturnal deactivation of the artificial urinary sphincter lessen the risk of urethral atrophy?

OBJECTIVES: To compare nocturnal deactivation with nocturnal activation of the artificial urinary sphincter (AUS) to determine whether nocturnal deactivation reduces the risk of urethral atrophy and subsequent recurrent incontinence. To the best of our knowledge, no review comparing these two approaches has been performed. METHODS: At the Mayo Clinic, all patients are instructed to deactivate their AUS at night; at Baylor, all patients keep their AUS activated all the time. At each institution, a group of consecutive men with comparable severe urinary incontinence after radical retropubic prostatectomy were selected; 61 and 46 patients from the Mayo Clinic and Baylor, respectively, were available for review. All Mayo Clinic patients strictly adhered to nocturnal deactivation of their AUS and all 46 patients from Baylor kept their AUS activated at all times, except during voiding. Each patient was reviewed for the long-term risk of subsequent reoperation, especially regarding recurrent incontinence due to urethral atrophy. RESULTS: Seventeen (27.8%) of the 61 patients from Mayo (mean follow-up 40 months) required a repeated operation. Of the 17 AUS failures, 6 (35%) were due to urethral atrophy. Of the 46 patients from Baylor (mean follow-up 28 months), 16 (34.7%) required a repeated operation. Of the 16 AUS failures, 10 (62%) were due to urethral atrophy. Overall, the patients who nocturnally deactivated their AUS had a 10% risk of atrophy-related incontinence compared with a 21% risk in the nocturnally activated group. CONCLUSIONS: Although not statistically significant, nocturnal deactivation appears to decrease the risk of urethral atrophy and recurrent incontinence (10% versus 21%). Nocturnal deactivation should be considered in men who are dry at night and have sufficient motivation to lessen the risk of urethral atrophy secondary to cuff compression.

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Effects of a 10-minute back rub on cardiovascular responses in healthy subjects.

This study determined the cardiovascular responses to a 10-minute back rub. Twelve healthy, college-age males and females (mean age = 22 years) volunteered to participate as subjects. Using an ABA design, the subjects tested for 10 minutes (Control #1) on a padded plinth lying on one side. During the Treatment period, the back rub was administered, which was followed by Control #2. Oxygen consumption (VO2) was determined via the Medical Graphics CPX/D metabolic analyzer, which also estimated cardiac output (Q) using the CO2 rebreathing (equilibrium) method. A repeated measures ANOVA was performed to statistically compare the cardiovascular responses across the three periods. The back rub, when compared to Control #1, had no significant effect on VO2, but the central and peripheral components of VO2 were changed. Cardiac output was decreased as a result of the decreased stroke volume (SV), as a function of the increased peripheral vascular resistance (PVR). We also found an increase in the extraction of oxygen (a-vO2 diff) in the peripheral tissues. These results indicate that the VO2 response during the back rub was achieved by reciprocal central (SV,Q) and peripheral (a-vO2 diff) adjustments. Following the back rub, (i.e., Control #2 vs. Treatment), the decrease in VO2, VCO2, Ve, and a-vO2 diff appears to indicate that it was effective in inducing relaxation. Since HR, SV, and Q were unchanged, the VO2 response was a result of the decreased a-vO2 diff. Hence, the findings suggest certain positive implications for the health care industry.