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Heat treatment was one of the first transformative technologies in the southern African Middle Stone Age (MSA), with many studies in the Cape coastal zone of South Africa identifying it as an essential step in the preparation of silcrete prior to its use in stone tool manufacture. To date, however, no studies have investigated whether heat treatment is necessary for all silcrete types, and how geographically widespread heat treatment was in the subcontinent. The aim of this study is to investigate experimentally whether heat treatment continued further north into the Kalahari Desert of Botswana and northernmost South Africa, the closest area with major silcrete outcrops to the Cape. For this we analyse the thermal transformations of silcrete from both regions, proposing a comprehensive model of the chemical, crystallographic and 'water'-related processes taking place upon heat treatment. For the first time, we also explore the mobility of minor and trace elements during heat treatment and introduce a previously undescribed mechanism-steam leaching-causing depletion of a limited number of elements. The results of this comparative study reveal the Cape and Kalahari silcrete to respond fundamentally differently to heat treatment. While the former can be significantly improved by heat, the latter is deteriorated in terms of knapping quality. These findings have important implications for our understanding of the role of fire as a technical solution in MSA stone tool knapping, and for the extension of its use in southern Africa. Silcrete heat treatment-at least in the form we understand it today-may have been a strictly regional phenomenon, confined to a narrow zone along the west and south coast of the Cape. On the basis of our findings, silcrete heat treatment should not be added as a new trait on the list of behaviours that characterise the MSA of the southern African subcontinent.

Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality. With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.

In this paper, we have investigated the combined effects of Newtonian heating and internal heat generation/absorption in the two-dimensional flow of Eyring-Powell fluid over a stretching surface. The governing non-linear analysis of partial differential equations is reduced into the ordinary differential equations using similarity transformations. The resulting problems are computed for both series and numerical solutions. Series solution is constructed using homotopy analysis method (HAM) whereas numerical solution is presented by two different techniques namely shooting method and bvp4c. A comparison of homotopy solution with numerical solution is also tabulated. Both solutions are found in an excellent agreement. Dimensionless velocity and temperature profiles are plotted and discussed for various emerging physical parameters.

Background Accelerated malignant behaviors induced by insufficient thermal ablation have been increasingly reported, however, the exact mechanisms are still unclear. Here, we investigated the importance of the extracellular matrix (ECM) in modulating the progression of residual hepatocellular carcinoma (HCC) after heat treatment. Methods Heat-exposed residual HCC cells were cultured in different ECM gels. We used basement membrane gel (Matrigel) to simulate the normal microenvironment and collagen I to model the pathological stromal ECM. The alterations of morphology and parameters of proliferation, epithelial-mesenchymal transition (EMT) and stemness were analyzed in vitro and in vivo. Results Increased collagen I deposition was observed at the periablational zone after incomplete RFA of HCC in a xenograft model. The markers of cell proliferation, EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were significantly induced by collagen I as compared to Matrigel ( p values all < 0.05). Importantly, collagen I induced the activation of ERK phosphorylation in heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I-promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I promoted the in vivo tumor progression of heat-exposed residual HCC cells, and sorafenib markedly reversed the collagen I-mediated protumor effects. Conclusions Our findings demonstrate that collagen I could enhance the aggressive progression of residual HCC cells after suboptimal heat treatment and sorafenib may be a treatment approach to thwart this process.

Background Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results Our search identified 6886 studies; 22 studies ( n  = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75–0.96]; p  = 0.008) but not mortality (OR 0.88 [95% CIs 0.62–1.25]; p  = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).

Background Calf muscle strain and Achilles tendon injuries are common in many sports. For the treatment of muscular and tendinous injuries, one of the newer approaches in sports medicine is capacitive-resistive electric transfer therapy. Our objective was to analyze this in vitro, using invasive temperature measurements in cadaveric specimens. Methods A cross-sectional study designed with five fresh frozen cadavers (10 legs) were included in this study. Four interventions (capacitive and resistive modes; low- and high-power) was performed for 5 min each by a diathermy “T-Plus” device. Achilles tendon, musculotendinous junction and superficial temperatures were recorded at 1-min intervals and 5 min after treatment. Results With the low-power capacitive protocol, at 5 min, there was a 25.21% increase in superficial temperature, a 17.50% increase in Achilles tendon temperature and an 11.27% increase in musculotendinous junction temperature, with a current flow of 0.039 A ± 0.02. With the low-power resistive protocol, there was a 1.14% increase in superficial temperature, a 28.13% increase in Achilles tendon temperature and an 11.67% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.063 A ± 0.02. With the high-power capacitive protocol there was an 88.52% increase in superficial temperature, a 53.35% increase in Achilles tendon temperature and a 39.30% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.095 A ± 0.03. With the high-power resistive protocol, there was a 21.34% increase in superficial temperature, a 109.70% increase in Achilles tendon temperature and an 81.49% increase in musculotendinous junction temperature at 5 min, with a current flow of 0.120 A ± 0.03. Conclusion The low-power protocols resulted in only a very slight thermal effect at the Achilles tendon and musculotendinous junction, but current flow was observed. The high-power protocols resulted in a greater temperature increase at the Achilles tendon and musculotendinous junction and a greater current flow than the low-power protocols. The high-power resistive protocol gave the greatest increase in Achilles tendon and musculotendinous junction temperature. Capacitive treatments (low- and high-power) achieved a greater increase in superficial temperature.

Background The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. Results A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h ( p  = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1–4.0] vs. 4.2 [2.7–6.0] h, p  < 0.001), but temperature was also lower on admission (35.0 [34.2–35.6] vs. 35.3 [34.5–35.8]°C; p  = 0.02) and cooling rate was similar (0.4 [0.2–0.8] vs. 0.4 [0.2–0.6]°C/h; p  = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4–0.9] vs. 0.7 [0.5–1.0]°C; p  = 0.007), as was rewarming rate (0.31 [0.22–0.44] vs. 0.37 [0.29–0.49]°C/hour; p  = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p  = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p  = 0.24) between type of devices. Conclusions Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.

Chemotherapy-induced alopecia (CIA) represents the most distressing side-effect for cancer patients. Scalp cooling is currently the only treatment to combat CIA, yet little is known about its cytoprotective effects in human hair follicles (HF). We have previously established in vitro human keratinocyte models to study the effects of taxanes and anthracyclines routinely-used clinically and reported that cooling markedly-reduced or even completely-prevented cytotoxicity in a temperature dependent manner. Using these models (including HF-derived primary keratinocytes), we now demonstrate that cooling markedly attenuates cellular uptake of the anthracyclines doxorubicin and epirubicin to reduce or prevent drug-mediated human keratinocyte cytotoxicity. We show marked reduction in drug uptake and nuclear localization qualitatively by fluorescence microscopy. We have also devised a flow cytometry-based methodology that permitted semi-quantitative analysis of differences in drug uptake, which demonstrated that cooling can reduce drug uptake by up to ~8-fold in comparison to normal/physiological temperature, an effect that was temperature-dependent. Our results provide evidence that attenuation of cellular drug uptake represents at least one of the mechanisms underpinning the ability of cooling to rescue human keratinocytes from chemotherapy drug-cytotoxicity, thus supporting the clinical efficacy of scalp cooling.

his study assessed the effectiveness of head cooling during exercise in the heat on cognitive performance, either alone or with ice ingestion. Ten healthy males, non-acclimatized to heat, ran (70% V̇O2peak) for 2×30 min in heat (35 ± 0.9°C, 68.2 ± 6.9% RH). Participants completed 3 trials: 10 min of head cooling during exercise (HC); precooling with crushed ice (7gikg-1) and head cooling during exercise (MIX); or no-cooling/control (CON). Working memory was assessed using the automated operation span task (OSPAN) and serial seven test (S7). Following MIX, S7 scores were improved compared to CON (12 ± 9.5, p = 0.004, d = 1.42, 0.34-2.28) and HC (4 ± 5.5, p = 0.048, d = 0.45, -0.47 to 1.3) during exercise. Moderate to large effect sizes were recorded for S7 and OSPAN following MIX and HC compared to CON, suggesting a tendency for improved cognitive performance during exercise in heat. Following precooling (MIX), core body temperature (Tc) and forehead temperature (Th) were lower compared to baseline (-0.75 ± 0.37°C, p < 0.001; -0.31 ± 0.29°C, p = 0.008, respectively) but not in HC or CON (p > 0.05). Thermal sensation (TS) was lower in MIX and HC compared to CON during exercise (p < 0.05). The reduction in Tc, Th and TS with MIX may have attenuated the effect of heat and subsequently improved working memory during exercise in heat.

Background Sepsis is often treated with penicillin-binding protein 3 (PBP-3) acting β-lactam antibiotics, such as piperacillin-tazobactam, cefotaxime, and meropenem. They cause considerable bacterial structural changes and have in vitro been associated with an increased inflammatory response. In a clinically relevant large animal sepsis model, our primary aim was to investigate whether bacteria killed by a PBP-3-active antibiotic has a greater effect on the early inflammatory response and organ dysfunction compared with corresponding amounts of live or heat-killed bacteria. A secondary aim was to determine whether the addition of an aminoglycoside could mitigate the cefuroxime-induced response. Method Killed or live Escherichia coli were administrated as a 3-h infusion to 16 healthy pigs in a prospective, randomized controlled interventional experimental study. Cefuroxime was chosen as the PBP-3-active antibiotic and tobramycin represented the aminoglycosides. The animals were randomized to receive (I) bacteria killed by cefuroxime, (II) live bacteria, (III) bacteria killed by heat, or (IV) bacteria killed by the combination of cefuroxime and tobramycin. Plasma endotoxin, tumor necrosis factor alpha, interleukin-6, interleukin-10, leukocytes, and organ function were recorded at the start of the experiment and then hourly for 6 h. Results Differences in dynamics of concentration over time between the four treatment groups were found for the three cytokines ( p  < 0.001). Animals receiving cefuroxime-killed bacteria demonstrated higher responses than those receiving live ( p  < 0.05) or heat-killed bacteria ( p  < 0.01). The addition of tobramycin reduced the cefuroxime-induced responses ( p  < 0.001). The cytokine responses were associated with leucocyte activation that was further associated with pulmonary dysfunction and increases in lactate ( p  < 0.01). Conclusions In comparison with live or heat-killed bacteria, bacteria killed by a PBP-3-active antibiotic induced an increased inflammatory response that appears to be associated with deteriorated organ and cellular function. The addition of an aminoglycoside to the PBP-3-active antibiotic reduced that response.