Inaugural Review Prize 2023: The exercise hyperpnoea dilemma:A 21st‐century perspective

During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the ‘exercise hyperpnoea dilemma’ can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood‐gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory ‘engram’ encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till‐now intractable exercise hyperpnoea dilemma

Flora of an unusually diverse old growth forest in the southeastern Adirondacks

A lowland, virgin white pine-hemlock stand and associated old-growth habitats were studied at Pack Forest Preserve, Warren County, NY. An area of 48.1 acres, interrupted only by nature trails, has white pines up to 58 inches in diameter, and supports 355 native plant species-an unexpectedly high number, considering its location in the climatically severe Adirondack Mountains. This minimally disturbed old-growth forest and its associated wetlands are not only diverse, but essentially weed-free, making them ideal for future ecological research, botanical teaching and monitoring activities

Cadaveric renal transplantation at the University of Pittsburgh: a two and one-half-year experience with the point system.

From January 1, 1986 to July 30, 1988, 530 consecutive cadaver kidney transplantations were performed with patient selection by a point system that took into account time awaiting an organ, donor-recipient matching, degree of presensitization, and some less important factors. The effect of the system was to diminish judgmental factors in case selection which in the past, had probably operated to the disadvantage of "undesirable" potential recipients, including older ones. Primary 1-year graft survival (74%) and graft survival after retransplantation (71%) were lower than in the earlier time. However, the results with triple-drug therapy using CsA, AZA and P demonstrated 88% 1-year graft survival for primary graft recipients and 74% in highly sensitized patients, with comparable patient mortality. These latter observations provide some assurance that the concepts of equitable access and efficient utilization of a scarce resource are not mutually exclusive

Prevalence of liver fluke (Fasciola hepatica) in wild Red Deer (Cervus elaphus): coproantigen ELISA is a practicable alternative to faecal egg counting for surveillance in remote populations

Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p < 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable geographic, temporal, sex and age related differences in F. hepatica prevalence in wild Scottish Highland red deer

Kidney transplantation in Pittsburgh: experience and innovations.

1. The introduction of combined CsA and steroid treatment as the baseline immunosuppressive medication significantly enhanced the results of kidney transplantation in our series. But various other preexisting recipient or donor conditions may still have an important effect on kidney transplant survival and should not go unrecognized. 2. Living-related kidney transplants were almost totally abandoned at our institution. Reasons for this approach are the increased availability of cadaveric donor organs, the improved results with cadaveric transplants under CsA and the possible risks to the living donors. 3. Combined liver/kidney transplants have been shown to offer a favorable treatment modality for patients with endstage liver and renal failure. 4. A newly developed center-oriented Transplant Information Management System (TIMY) significantly facilitates the clinical and research tasks in our department. 5. An integrated, computerized scoring system for equitable allocation of donor organs has proven to be highly effective during routine clinical use