The Mockingbird Gap site is one of the largest Clovis sites in the western United States, yet it remains poorly known after it was tested in 1966-1968. Surface collecting and mapping of the site revealed a dense accumulation of Clovis lithic debris stretching along Chupadera Draw, which drains into the Jornada del Muerto basin. We conducted archaeological testing and geoarchaeological coring to assess the stratigraphic integrity of the site and gain clues to the paleoenvironmental conditions during the Clovis occupation. The 1966-1968 excavations were in stratified Holocene eolian sand and thus that assemblage was from a disturbed content. An intact Clovis occupation was found elsewhere in the site, embedded in the upper few centimeters of a well-developed buried Bt horizon formed in eolian sand, representing the regional Clovis landscape. Coring in Chupadera Draw revealed ϳ11 m of fill spanning the past ϳ11,000 14 C years. The stratified deposits provide evidence of flowing and standing water on the floor of the draw during Clovis times, a likely inducement to settlement.

Effective treatment for AML is challenging due to the presence of clonal heterogeneity and the evolution of polyclonal drug resistance. Here, we report that TP-0903 has potent activity against protein kinases related to STAT, AKT, and ERK signaling, as well as cell cycle regulators in biochemical and cellular assays. In vitro and in vivo, TP-0903 was active in multiple models of drug-resistant FLT3 mutant AML, including those involving the F691L gatekeeper mutation and bone marrow microenvironment–mediated factors. Furthermore, TP-0903 demonstrated preclinical activity in AML models with FLT3 -ITD and common co-occurring mutations in IDH2 and NRAS genes. We also showed that TP-0903 had ex vivo activity in primary AML cells with recurrent mutations including MLL -PTD, ASXL1 , SRSF2 , and WT1 , which are associated with poor prognosis or promote clinical resistance to AML-directed therapies. Our preclinical studies demonstrate that TP-0903 is a multikinase inhibitor with potent activity against multiple drug-resistant models of AML that will have an immediate clinical impact in a heterogeneous disease like AML.

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Whipple disease is a rare multisystemic disorder of infectious aetiology caused by Tropheryma whipplei. Pulmonary hypertension is a rare association for which the underlying pathophysiological mechanism is unclear. Our patient was a 54-year-old man with a 1-year history of progressive polyarticular arthritis, and worsening respiratory and gastrointestinal symptoms. Pulmonary artery catheterisation demonstrated moderate-to-severe pulmonary hypertension. Duodenal biopsies, with electron microscopy, were diagnostic of Whipple disease. Involvement by Whipple disease was also evident in the stomach, bone marrow and pulmonary pleura. A 2-week course of intravenous ceftriaxone was initiated and this was followed by a 1-year course of trimethoprim/sulfamethoxazole (160/800), once daily. Nine months into antibiotic treatment, a repeat echocardiogram showed normalisation of the size and function of the cardiac chambers, including the right atrium and right ventricle. There was complete resolution of the severe tricuspid insufficiency and pulmonary hypertension. Whipple disease is not generally considered as a possible cause of pulmonary hypertension but such awareness is important given that it may be potentially reversible with antibiotic therapy.