Naturally acquired immunity to Plasmodium pitheci in Bornean orangutans (Pongo pygmaeus).

Naturally acquired immunity to the different types of malaria in humans occurs in areas of endemic transmission and results in asymptomatic infection of peripheral blood. The current study examined the possibility of naturally acquired immunity in Bornean orangutans, Pongo pygmaeus, exposed to endemic Plasmodium pitheci malaria. A total of 2140 peripheral blood samples were collected between January 2017 and December 2022 from a cohort of 135 orangutans housed at a natural forested Rescue and Rehabilitation Centre in West Kalimantan, Indonesia. Each individual was observed for an average of 4.3 years during the study period. Blood samples were examined by microscopy and polymerase chain reaction for the presence of plasmodial parasites. Infection rates and parasitaemia levels were measured among age groups and all 20 documented clinical malaria cases were reviewed to estimate the incidence of illness and risk ratios among age groups. A case group of all 17 individuals that had experienced clinical malaria and a control group of 34 individuals having an event of >2000 parasites µL−1 blood but with no outward or clinical sign of illness were studied. Immature orangutans had higher-grade and more frequent parasitaemia events, but mature individuals were more likely to suffer from clinical malaria than juveniles. The case orangutans having patent clinical malaria were 256 times more likely to have had no parasitaemia event in the prior year relative to asymptomatic control orangutans. The findings are consistent with rapidly acquired immunity to P. pitheci illness among orangutans that wanes without re-exposure to the pathogen.

Plasmodium pitheci malaria in Bornean orang-utans at a rehabilitation centre in West Kalimantan, Indonesia.

BACKGROUND: Plasmodial species naturally infecting orang-utans, Plasmodium pitheci and Plasmodium silvaticum, have been rarely described and reportedly cause relatively benign infections. Orang-utans at Rescue Rehabilitation Centres (RRC) across the orang-utan natural range suffer from malaria illness. However, the species involved and clinical pathology of this illness have not been described in a systematic manner. The objective of the present study was to identify the Plasmodium species infecting orang-utans under our care, define the frequency and character of malaria illness among the infected, and establish criteria for successful diagnosis and treatment. METHODS: During the period 2017-2021, prospective active surveillance of malaria among 131 orang-utans resident in a forested RRC in West Kalimantan (Indonesia) was conducted. A total of 1783 blood samples were analysed by microscopy and 219 by nucleic acid based (PCR) diagnostic testing. Medical records of inpatient orang-utans at the centre from 2010 to 2016 were also retrospectively analysed for instances of symptomatic malaria. RESULTS: Active surveillance revealed 89 of 131 orang-utans were positive for malaria at least once between 2017 and 2021 (period prevalence = 68%). During that period, 14 cases (affecting 13 orang-utans) developed clinical malaria (0.027 attacks/orang-utan-year). Three other cases were found to have occurred from 2010-2016. Sick individuals presented predominantly with fever, anaemia, thrombocytopenia, and leukopenia. All had parasitaemias in excess of 4000/µL and as high as 105,000/µL, with severity of illness correlating with parasitaemia. Illness and parasitaemia quickly resolved following administration of artemisinin-combined therapies. High levels of parasitaemia also sometimes occurred in asymptomatic cases, in which case, parasitaemia cleared spontaneously. CONCLUSIONS: This study demonstrated that P. pitheci very often infected orang-utans at this RRC. In about 14% of infected orang-utans, malaria illness occurred and ranged from moderate to severe in nature. The successful clinical management of acute pitheci malaria is described. Concerns are raised about this infection potentially posing a threat to this endangered species in the wild.

When Does Physician Use of AI Increase Liability?

An increasing number of automated and artificial intelligence (AI) systems make medical treatment recommendations, including personalized recommendations, which can deviate from standard care. Legal scholars argue that following such nonstandard treatment recommendations will increase liability in medical malpractice, undermining the use of potentially beneficial medical AI.  However, such liability depends in part on lay judgments by jurors: when physicians use AI systems, in which circumstances would jurors hold physicians liable? Methods: To determine potential jurors' judgments of liability, we conducted an online experimental study of a nationally representative sample of 2,000 U.S. adults. Each participant read 1 of 4 scenarios in which an AI system provides a treatment recommendation to a physician. The scenarios varied the AI recommendation (standard or nonstandard care) and the physician's decision (to accept or reject that recommendation). Subsequently, the physician's decision caused harm. Participants then assessed the physician's liability. Results: Our results indicate that physicians who receive advice from an AI system to provide standard care can reduce the risk of liability by accepting, rather than rejecting, that advice, all else being equal. However, when an AI system recommends nonstandard care, there is no similar shielding effect of rejecting that advice and so providing standard care. Conclusion: The tort law system is unlikely to undermine the use of AI precision medicine tools and may even encourage the use of these tools.

Quantitative bond energetics in atomic-scale junctions.

A direct measurement of the potential energy surface that characterizes individual chemical bonds in complex materials has fundamental significance for many disciplines. Here, we demonstrate that the energy profile for metallic single-atom contacts and single-molecule junctions can be mapped by fitting ambient atomic force microscope measurements carried out in the near-equilibrium regime to a physical, but simple, functional form. We extract bond energies for junctions formed through metallic bonds as well as metal-molecule link bonds from atomic force microscope data and find that our results are in excellent quantitative agreement with density functional theory based calculations for exemplary junction structures. Furthermore, measurements from a large number of junctions can be collapsed to a single, universal force-extension curve, thus revealing a surprising degree of similarity in the overall shape of the potential surface that governs these chemical bonds. Compared to previous studies under ambient conditions where analysis was confined to trends in rupture force, our approach significantly expands the quantitative information extracted from these measurements, particularly allowing analysis of the trends in bond energy directly.