As Dr. Thomson eloquently notes in his valuable letter [1], underlying respiratory diseases appear to be less of a risk factor for poor outcome in COVID-19 patients than either underlying cardiovascular disease or diabetes. This intriguing finding emerged from several studies that examined underlying medical conditions in COVID-19 patients.In a single-center retrospective analysis of critically ill adults admitted to the intensive care unit of a hospital from China between late December 2019 and January 26, 2020, 22% of the non-survivors had cerebrovascular disease, 22% had diabetes, and 6% had chronic respiratory disease [2]. The analysis of data from patients with laboratory-confirmed COVID-19 from hospitals in China through January 29, 2020 found that 16.2% of those with serious disease had diabetes, 23.7% had hypertension, and 3.5% had chronic obstructive pulmonary disease [3]. A study of electronical medical records of COVID-19 patients admitted between January 16 and February 3, 2020 to a hospital from Wuhan found that hypertension and diabetes mellitus, the most common comorbidities, were present in 37.9%, 13.8%, of the patients with severe disease, respectively, but only in 3.4% of the patients with chronic obstructive pulmonary disease [4]. Finally, an analysis of all COVID-19 cases reported through February 11, 2020, extracted from the Infectious Disease Information System in China, found that case fatality rates in individuals with cardiovascular disease, chronic respiratory disease, and diabetes were 10.5%, 6.3%, and 7.3% respectively, as compared to 0.9% among patients with no comorbidities [5]. In a case series of COVID-19 patients hospitalized in Wuhan, China, ICU patients were more likely to have underlying diabetes than patients that did not receive ICU care (22.2% vs 5.9%) [6].The studies mentioned above did not stratify patients by therapies they were receiving. However, one commonality between cardiovascular disease and diabetes is that they are often treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-I receptor blockers (ARBs), widely used to inhibit the formation and action of angiotensin II.ACE shares 42% amino acid identity with ACE2 [7], a membrane-bound aminopeptidase [8] extensively expressed on type II human alveolar cells [9]. The genes encoding these two proteins are thought to have emerged by duplication [10]. ACE2 is distributed on many tissues and shows highest expression levels in the heart, kidney, lung, small intestine, and testis [11]. On the apical surface of polarized respiratory epithelial cells, ACE2 is a crucial and primary receptor for the cellular entry of SARS-CoV, the virus that caused the 2002-2003 SARS outbreak [12-16]. SARS-CoV binding to ACE2 mediates entry into human or animal cells [17]. ACE2 is also the receptor for SARS-CoV-2, the etiologic agent of COVID-19 [18]. Structural analyses indicate that SARS-CoV-2 binds the ACE2 receptor with a 10-20-fold higher affinity than SARS-CoV [19, 20].The entry of SARS-CoV and SARS-CoV-2 into their target cells is mediated by the viral spike (S) glycoprotein, which is located on the outer envelope of the virion [21]. The S glycoprotein has two functional subunits, S1, which binds the cellular receptor, and S2, which contains domains required for the fusion between viral and cellular membranes [22, 23]. Viral binding and membrane fusion represent the initial and critical steps during the infection cycle of the coronavirus [24] and the first step in establishing the infection [25, 26]. Binding is followed by internalization of ACE2 and down‐regulation of its activity on the cell surface [27-29].SARS-CoV binds ACE2 through a region of the viral S1 subunit called the minimal receptor-binding domain (RBD) [17]. RBD is the most important determinant of the SARS-CoV host range, and studies about the “species jump” during the 2002-2003 SARS outbreak revealed that changes of only one or two amino acids in this region were sufficient to make the virus “jump” to a new host [26, 30, 31].ACE and ACE2 are two members of the renin angiotensin system that negatively regulate each other [32, 33] and are distinct in their substrate specificity and function [34]. ACE converts angiotensin I to angiotensin II and mediates aldosterone release, vasoconstriction, sodium retention, cell proliferation, and organ hypertrophy [35]. ACE2 cleaves a single residue from angiotensin I to form angiotensin-(1-9), and a single residue from angiotensin II to form angiotensin-(1-7). In humans, ACE2 has a 400-fold higher catalytic efficiency when it uses angiotensin II as a substrate as compared to when it uses angiotensin I [36]. ACE2 and angiotensin-(1-7), through the Mas receptors, oppose ACE and mediate vasodilation and anti-proliferative, anti-hypertrophic, cardioprotective, and reno-protective effects [8, 35, 37]. ACE2 has physiological and pathological importance [25] and its dysregulation was implicated in heart disease, hypertension, and diabetes [36, 38-40]. ACE2 is not inhibited by ACE inhibitors [32] and several studies indicate that the ACE2/Angiotensin-(1-7)/Mas axis has anti-inflammatory effects [41, 42].It was recently hypothesized that treatment with ACE inhibitors and/or ARBs may lead to ACE2 overexpression and this could increase the risk of severe COVID-19 [43], possibly by increasing the internalization of SARS-CoV-2. Several lines of evidence indicate that pharmacological manipulation of the renin-angiotensin-aldosterone pathway could affect ACE2 receptor levels. In animal studies, the selective blockade of angiotensin II synthesis or activity increased cardiac Ace2 gene expression and activity [44, 45], and treatment with ARBs increased the levels of cardiovascular ACE2 receptors [46-49]. While this link is thought-provoking as a possibility, there isn’t currently sufficient evidence to contemplate changing patients’ existing therapeutic regimens in order to minimize their risk of COVID-19 complications. The first clinical evidence exploring this link indicated that the use of ACEI and ARBs appear to improve the clinical outcome of COVID-19 patients with hypertension [50]. We will only learn about any possible associations, along with their magnitude and direction, from carefully conducted and adequately powered clinical trials.It is also important to consider that an increase in ACE2 levels does not necessarily entail a negative impact for the course of COVID-19. ACE2, by forming angiotensin-(1-7) from angiotensin II, could diminish the deleterious effects of angiotensin II and, consequently, it is also possible that ACE inhibitors or ARBs could, in fact, lower the risk of complications [51]. However, increased ACE2 and the formation of angiotensin-(1-7), by inhibiting COX-2, could exert anti-inflammatory effects [52, 53], underscoring the multitude of possible effects and the need to conduct studies to interrogate these connections. Finally, it is not known whether an increase in the expression of ACE2 would also lead to an increased shedding and increased levels of soluble ACE2, which could act as a decoy receptor and lower viral entry into cells [54]. In support of this, recombinant human ACE2 ameliorated the lung injury induced by the avian influenza H5N1 virus in mice [55]. It is also important to consider that from the relatively limited amount of human data, plasma ACE2 activity does not appear to be statistically different between individuals taking ACE inhibitors or ARBs and those not taking these medications, but these results do not reflect the levels of cellular receptors [56]. Structural analyses indicate that the binding of the SARS-CoV spike protein to ACE2 does not occlude the catalytically active site of the receptor [26, 57], and it was hypothesized that angiotensin II binding to ACE2 could induce a conformational change in the receptor, which will no longer be favorable for SARS-CoV-2 binding [54]. The mining of existing datasets, preclinical studies, and clinical trials will help shed light on these complex and sometimes conflicting scenarios.A decrease in the number of ACE2 receptors appears to be involved in acute lung injury and cardiovascular pathology [58, 59], and may be detrimental during coronavirus infection. A mouse Ace2 knockout developed severe cardiac contractility defects and increased angiotensin II levels, and the additional deletion of Ace rescued this phenotype [60]. In acute lung injury models, the loss of Ace2precipitated severe acute lung failure, and this was attenuated by the exogenous recombinant human ACE2 in both Ace2 knock-out and in wild-type mice [59]. Attenuation of the Ace2 catalytic function perturbed the pulmonary renin-angiotensin-aldosterone system and increased inflammation and vascular permeability [61], and Ace2 overexpression decreased lung inflammation in an animal model of acute lung injury [62]. In vitro and in experimental animals, SARS-CoV and the SARS-CoV spike protein downregulated ACE2 expression [12, 28]. In mice with lung injury, injection of the SARS-CoV spike protein worsened the acute lung failure and caused lung edema, increased vascular permeability, and decreased lung function, and this pathology was attenuated by blocking the renin-angiotensin-aldosterone pathway [12]. Thus, animals infected with SARS-CoV or treated with the spike protein resemble Ace2 knockout animals [12]. It is relevant that a pilot study of patients with acute respiratory distress syndrome reported the accumulation of angiotensin I and the decrease of angiotensin-(1-9), indicating decreased ACE2 activity, among non-survivors [63]. Thus, SARS-CoV and SARS-CoV-2 might contribute to severe respiratory symptomatology partly because the viruses, by binding the ACE2 receptors, also deregulate protective pathways in the lungs.Thus, either increased or decreased numbers of pulmonary ACE2 receptors may be detrimental during SARS-CoV or SARS-CoV-2 infection, most likely for distinct reasons. An increased number of ACE2 receptors may lead to a higher viral load and more severe clinical disease. Diabetes increases ACE2 expression, as shown in several experimental models, and the resulting increased viral load might explain the more severe course of COVID-19 in diabetic patients [64, 65]. Interestingly, in a rodent model of diabetes, ibuprofen inhibited the ACE/angiotensin II/angiotensin type 1 receptor axis and enhanced the ACE2/angiotensin-(1-7)/Mas receptor axis [66]. Too few functional ACE2 receptors, which decrease even more as a result of high viral loads and enhanced receptor internalization [67], might exacerbate acute lung injury, increase angiotensin II levels, and alter the balance between pro- and anti-inflammatory responses. It is relevant that in a study on twelve COVID-19 patients from China, plasma angiotensin II levels were markedly elevated as compared to healthy control individuals, and linearly associated with the viral load and with the lung injury [68]. The animal studies that documented an age-dependent decrease in ACE2 expression in the lung and the aortic might also explain, at least in part, the age-dependent increase in the risk of serious COVID-19 complications [69, 70].SARS-CoV can also bind cells through alternative receptors that include the C-type lectins DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) and/or L-SIGN (liver/lymph node-SIGN) [14, 71-73]. It will be critical to understand the potential involvement of the same, or alternative receptors in the pathogenesis of COVID-19.It has been less clear why SARS-CoV and SARS-CoV-2 lead to severe lung disease [57], in contrast to other, previously known coronaviruses, which usually result in mild upper respiratory infections and cause pneumonia only rarely, mostly in newborn, the elderly, and immunocompromised individuals [74-77]. One of the possibilities advanced for SARS is that the burden of viral replication and the immune status of the host may both shape the severity of the infection [57, 78, 79]. The same might be true for COVID-19, and further exploring the link between viral burden, chronic medical conditions, long-term medication usage, and the severity of the infection will be critical.An important lesson from SARS and MERS is the association between the incubation period and disease severity. For any infectious disease, the incubation period varies among individuals, even for the same outbreak, and depends on the initial infective dose, the speed of pathogen replication within a host, and host defense mechanisms [80]. During the 2002-2003 SARS outbreak, a study in Hong Kong revealed that patients with shorter incubation times developed more severe disease [81]. The same was found in MERS patients from South Korea, where longer incubation times were associated with a lower risk of death [82]. Interestingly, during the SARS outbreak in Hong Kong, healthcare workers, who have a higher infecting dose, had 34% shorter median incubation times than non-healthcare workers [83]. It will be interesting to examine whether the same is true for SARS-CoV-2, and whether the incubation period is different in COVID-19 patients when they are stratified by age, coexisting morbidities, and therapies they receive for chronic diseases. While the association between the incubation period and mortality might simply indicate that the disease was confirmed earlier in patients with longer incubations, and reflect earlier treatment opportunities [82], it is also plausible that high viral loads might mediate the link between the two.Two factors decisive for the successful control of outbreaks are the ability to isolate asymptomatic individuals and the ability to trace and quarantine their contacts [84, 85]. Several studies reported asymptomatic shedding of SARS-CoV-2, indicating that asymptomatic carriers, or individuals with very mild symptoms, may sustain transmission [86-89]. For example, nearly 18% of the passengers who tested positive for SARS-CoV-2 on the Diamond Princess cruise ship were asymptomatic [88]. Another valuable finding that emerged from the COVID-19 outbreak analysis in Singapore, and has a strong impact on infection control, is that after becoming asymptomatic, some patients continued to shed the virus for up to several days. In one instance, a patient continued to have detectable respiratory shedding, as shown by PCR, for eight consecutive days after becoming asymptomatic [90]. Another study revealed that several children with COVID-19 persistently tested positive for viral RNA on fecal swabs after their nasopharyngeal cultures became negative. Even though replication-competent virus was not detected in the fecal swabs, this finding leaves open the possibility of SARS-CoV-2 fecal-oral transmission [91]. These findings illustrate the challenges in understanding SARS-CoV-2 transmission and in identifying infected individuals, tracing their contacts, and implementing preparedness plans. One of the absolute requirements, to clarify these questions and overcome these obstacles, is ensuring the prompt and large-scale testing of symptomatic individuals and of their asymptomatic contacts. This, together with the social distancing measures, are currently our only available assets in facing a pandemic that, even though it was preceded by multiple warnings in recent years, is unlike any other infectious disease that we experienced in modern history.

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Specific therapies in pregnant women are discussedThe health crisis caused by the novel SARS-cov-2 (2019-nCoV) related pandemic requires urgent and necessary therapeutic response. Pregnant women are just as exposed as the general population and should not be excluded, because of their status, from discussions on effective and well tolerated candidate treatments. While in countries that have opted for national containment, daily non-emergency medical and surgical activities are suspended, obstetric services continue to operate relentlessly and are experiencing a surge in so-called ”at-risk” pregnancies. Some countries have now recommended routine screening of all pregnant women 1 but the low availability and performance of the current tests limits their use. Management of an infected pregnant women is essentially conditioned by maternal symptomatology. Women with little or no symptoms do not require routine treatment or in-patient care and simply need to be monitored for up to 15 days for evidence of respiratory deterioration. In the absence of validated specific treatment, the primary approach to therapy is mainly symptomatic and delivery is considered in the event of critical respiratory distress in order to maximize oxygenation and lung capacity2–4 . However, it has been reported that women with respiratory signs may be given antiviral treatment to improve their clinical condition 2,4To date, there is no proven effective strategy, although many teams are working tirelessly to identify an effective treatment. Four molecules are leading in this race:1) Remdesivir is a novel nucleotide analogue prodrug which incorporates into nascent viral RNA chains and results in pre-mature termination. Its effectiveness has been already demonstrated against others coronaviruses such as SARS-Cov and MERS-Cov5, and it has proven to be highly effective on in vitro 2019-nCoV infection6. Compassionate use in human were also reported 7 and phase 3 studies are currently underway.2) (Hydroxy)chloroquine has been known for years because of its effectiveness in the treatment of inflammatory diseases and against malaria. Recent studies have shown antiviral effects of chloroquine and in vitro studies concluded that it was highly effective in the control of 2019-nCoV 6,8. Elevation of endosomal pH and interference with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2 conduct to block virus infection. (Hydroxy)chloroquine has been used in 2019-nCoV infected humans with highly controversial restuls9,10 and well-designed randomized studies should be available soon.3) Lopinavir, a viral protease inhibitor, with its pharmacological booster Ritonavir (LPV/R) are commonly used in HIV positive patients. It has already been used for SARS-Cov. Some countries such as China and India approved its use in symptomatic infected patients although a first randomized, controlled, open-label trial showed no benefit of LPV/R over standard care in patients with severe 2019-nCoV disease11.4) Ribavirin, is a guanosine analog that interferes with the replication of RNA and DNA viruses. It has been used for years in the treatment of chronic hepatitis C. Based on its direct anti‐viral activity against 2019‐nCoV in vitro and some evidence for its potential efficacity during the prior SARS-Cov and MERS-Cov outbreaks, it has been suggested as a potential candidate for the treatment of 2019-nCoV diease12. 2019-nCoV infected patients treated with Ribavirin have been reported by Chinese studies4,13but its exact benefit remains to be demonstrated in well designed randomized studies as well.To date, all four drugs are being independently tested in Phase 3 studies, mostly national, to investigate their efficacy and safety in the management of 2019-nCoV disease. Several European countries have also set up, as a result of joint efforts since mid-March, a randomized, multicentre, open-label trial to evaluate and compare the efficacy and toxicity of the first three treatments mentioned above.14With regard to the possibility of treating pregnant patients with these molecules, few data are available for Remdesivir. Only one study reports its use in six pregnant women in a randomized trial during Ebola epidemics. The authors reported no adverse effect15.Many more pharmacological studies on maternal-fetal tolerance of Hydroxy(chloroquine), Lopinavir and Ribavirin are available. The historical use of (hydroxy)chloroquine in antimalarial treatment, but also in connective tissue diseases, has resulted in a well-documented safety and tolerance profile in pregnant women16. Animal studies, undertaken during the Zika virus epidemic, have also suggested that chloroquine may also reduce the risk of viral transplacental transmission to the fetus17. The optimal dosage to be used in pregnant women will have to be specified, but it appears that there is no pharmacokinetic difference between chloroquine and its major metabolite between pregnant and non-pregnant women18. With respect to the use of protease inhibitors during pregnancy, such as Lopinavir, some teams have reported an increased risk of preterm delivery. However, a specific analysis of more than 4,000 pregnant women found a similar incidence and rate of adverse pregnancy outcomes than in controls at all three trimesters of pregnancy, including preterm birth, low birth weight and birth defects19. Significant teratogenic effects have been demonstrated in all animal species exposed to Ribavirin, it is therefore currently contraindicated in pregnant women and in their male sexual partners, although the ribavirin pregnancy registry did not bring evidence of teratogenicity in humans20.The use of antiviral therapy in infected pregnant patients should follow the same indication as in the general population, but some obstetric specificities should be emphasized.1) The main goal should be to slow down and at best stop the clinical progression of the disease, i.e to remain asymptomatic and to avoid progression to acute respiratory distress syndrome in symptomatic cases. In the latter, the obstetrician is often called on to perform an emergency delivery and thus to induce extreme prematurity. Expert consensus provided obstetric guidance, but the management of cases at between 25 and 32 weeks’ remains challenging in the absence of effective antiviral treatment1.2) The second objective would be to rapidly decrease viral load and duration of contagiousness in infected pregnant women. The majority of them are doing well, but the infection can disrupt their obstetrical calendar. Some procedures need to be performed at a specific age, such as first trimester serum markers, ultrasound examinations, chorionic villi sampling (CVS). The same applies to access to termination of pregnancy. All such procedures may indeed be delayed, either to limit contagion, to limit the burden on the health care team (due to reinforced barrier measures…) or in the particular case of CVS/amniocentesis, to limit the theoretical risk of fetal transmission.3) Finally, the third advantage could be to introduce preventive treatment in case of maternal contact with an infected person, similar to what is done for seasonal influenza and oseltamivir21.The use of immunotherapy such as Tocilizumab, plasma of recovered coronavirus patient, Interferons, were not discussed here as they are currently understudy only for critically ill COVID-19 patients. No place for these treatments in a patient who is still pregnant should be considered for the time being, since if the pregnant woman presents a very severe form, the birth will be considered as a priority.The results of the Phase 3 therapeutic studies should be available soon. However, it is unfortunate that infected pregnant women are not included in any appropriate research protocols. Consequently, in this period of pandemic, mutual exchanges of experience between all countries’ maternity hospitals must be carried out in order to ensure the best possible management of infected pregnant women.

Structural characterization of alternatively folded and partially disordered protein conformations remains challenging. Outer surface protein A (OspA) is a pivotal protein in Borrelia infection, which is the etiological agent of Lyme disease. OspA exists in equilibrium with intermediate conformations, in which the central and the C-terminal regions of the protein have lower stabilities than the N-terminal. Here, we characterize pressure- and temperature-stabilized intermediates of OspA by nuclear magnetic resonance spectroscopy combined with paramagnetic relaxation enhancement (PRE). We found that the C-terminal region of the intermediate was partially disordered; however, it retains weak specific contact with the N-terminal region, owing to a twist of the central β-sheet and increased flexibility in the polypeptide chain. The disordered C-terminal region of the pressure-stabilized intermediate was more compact than that of the temperature-stabilized form. Further, molecular dynamics simulation demonstrated that temperature-induced disordering of the β-sheet was initiated at the C-terminal region and continued through to the central region. An ensemble of simulation snapshots qualitatively described the PRE data from the intermediate and indicated that the intermediate structures of OspA may expose tick receptor-binding sites more readily than does the basic folded conformation.

Objectives: To investigate the mental status of pregnant women and to describe their obstetrical choices during the outbreak of COVID-19. Design: A cross-sectional study. Setting: Wuhan and Chongqing, two different epidemic areas. Population: A total of 1947 valid questionnaires were received. Methods: We collected information on demographic, pregnancy, and epidemic, along with their attitudes towards the epidemic, anxiety status and obstetrical choices. We described and compared the city-based distribution of all above factors, aiming to explain how anxiety and obstetrical choices existed and differed. Main Outcome Measures: To explore why differences existed, we estimated the impact of the epidemic on women’s anxiety by multivariable analysis. Results: Distribution differences could be seen between cities in employment status, household income, gestational age, fetal number, and exposure history. Women’s attitudes towards COVID-19 in Wuhan were more extreme than that in Chongqing. The anxiety rate was more than double in Wuhan (24.47%) compared to that in Chongqing (10.44%). Generally speaking, obstetrical choices were similar among the 1947 participants, but more obvious in Wuhan. Conclusions: Our study found that the outbreak aggravated prenatal anxiety, and the influence factors could be targets of mental care. Synchronously, vital obstetrical choices changed, followed by pertinent professional advice to prevent irreversible adverse pregnancy outcomes. Online platforms may play crucial roles to address patients’ needs in future PHEs. Funding: National Natural Science Foundation of China (No. 81771614 and No. 81771613), and the National Key Research and Development Program of China (No. 2016YFC1000407). Keywords: COVID-19; Pregnancy; Prenatal Anxiety; Obstetrical Choices.

In this paper, we investigate the decay properties of the thermoelastic Timoshenko system with past history in the whole space where the thermal effects are given by Cattaneo and Fourier laws. We obtain that both systems, Timoshenko-Fourier and Timoshenko-Cattaneo, have the same rate of decay (1+t)^{-(1/4)} and the regularity-loss type property is not present in some cases. Moreover, new stability number χ is introduced, such new number controls the decay rate of the solution with respect to the regularity of the initial data. To prove our results, we use the energy method in Fourier space to build an appropriate Lyapunov functionals that give the desired results.

Expansins have the remarkable ability to loosen plant cell walls and cellulose material without showing catalytic activity and therefore have potential applications in biomass degradation. To support the study of sequence-structure-function relationships and the search for novel expansins, the Expansin Engineering Database (ExED, https://exed.biocatnet.de) collected sequence and structure data on expansins from Bacteria, Fungi, and Viridiplantae, and expansin-like homologues such as carbohydrate binding modules, glycoside hydrolases, loosenins, swollenins, cerato-platanins, and EXPNs. Based on global sequence alignment and protein sequence network analysis, the sequences are highly diverse. However, many similarities were found between the expansin domains. Newly created profile hidden Markov models of the two expansin domains enable standard numbering schemes, comprehensive conservation analyses, and genome annotation. Conserved key amino acids in the expansin domains were identified, a refined classification of expansins and carbohydrate binding modules was proposed, and new sequence motifs facilitate the search of novel candidate genes and the engineering of expansins.

Density functional theory, or DFT, has become ubiquitous for chemical applications in research and in education. The exact functional at the foundation of DFT is unfortunately unknown, and issues arise when choosing an approximation for a specific application. With this tutorial review, we tackle the selection problem and many related ones, such as the choices of a basis set and of an integration grid, that are often overlooked by occasional practitioners and by more experienced users as well. We offer a practical approach in the form of a commented notebook containing 12 experiments that can be run on a simple computer in just a few hours. We propose this review as a primary source for those who are willing to include DFT in their everyday research or teaching activities in a way that reflects the research advances of the field in the last couple of decades

Aim The importance of patient expectations (PEs) on treatment outcomes is poorly understood in clinical practice. The aim of this review is to investigate the evidence behind association between pre-treatment PEs and treatment outcomes such as pain intensity (PI), level of function (LF) and health-related quality of life (HRQOL) among individuals with chronic low back pain (CLBP) Methods A systematic search was conducted for randomised controlled trials published between 1946 and May 2019 across major databases using the key MeSH terminologies. The association between PEs and PI, LF and HRQOL were extracted and categorized into positive, negative or no association for analysing the data. A descriptive synthesis was conducted and the association between PEs and PI, LF and HRQOL were reported. Results Among the total of 7 trials, 2 trials demonstrated a positive association between PEs and PI in short (≤ 6 weeks) and long term (> 6 months), while another 2 trials demonstrated no association at medium term (> 6 weeks - ≤ 6 months). About 4 trials demonstrated a positive significant association between PEs and LF, 2 at medium and 2 at long terms. The only available trial demonstrated no association between PEs and HRQOL at medium term. Conclusion Positive PEs as measured at the start of treatment is associated with PI. Inconclusive evidence exists on the association between PEs and LF. Limited studies show no evidence of association between PEs and HRQOL. Further studies with valid tools to measure PE are warranted among individuals with CLBP.

Leaf soluble sugars and starch are important components of nonstructural carbohydrates (NSCs), which are crucial for plant growth, development, and reproduction. Although there is a large body of research focusing on the regulation of plant NSC (soluble sugars and starch) concentrations, the response of foliar NSC concentrations to continuous nitrogen (N) and phosphorus (P) addition is still unclear, especially in tropical forests. Here, we used a long-term manipulative field experiment to investigate the response of leaf NSC concentrations to continuous N and P addition (3-, 5-, and 8-year fertilization) in a tropical forest in southern China. We found significant species-specific variation in leaf NSC concentrations in this tropical forest. Phosphorus addition dramatically decreased both leaf soluble sugar and starch concentrations, while N addition had no significant effects on leaf soluble sugar and starch concentrations. These results suggest that, in plants growing in P-limiting tropical soil, leaf NSC concentrations are regulated by soil P availability rather than N availability. Moreover, the negative relationships between NSC concentrations and leaf mass per area (LMA) revealed that NSCs could supply excess carbon (C) for leaf expansion under P addition. This was further supported by the increased structural P fraction after P fertilization in our previous study at the same site. We conclude that soil P availability strongly regulates leaf starch and soluble sugar concentrations in the tropical tree species included in this study. The response of leaf NSC concentrations to long-term N and P addition can reflect the close relationships between plant C dynamics and soil nutrient availability in tropical forests. Maintaining relatively higher leaf NSC concentrations in tropical plants can be a potential mechanism for adapting to P-deficient conditions.

Drop breakup experiments were carried out in a stirred tank using the high-speed online camera. Breakup behaviors of drop breakup time, multiple breakage, and breakup rate were investigated. Experimental results show that the drop breakup time is mainly controlled by the interfacial tension and drop diameter, while is almost independent of the rotating speed. Besides, the dispersed phase viscosity has a slight influence on the breakup time. An empirical correlation for the breakup time is proposed and is further verified by comparing with the results of Solsvik and Jakobsen (Chem. Eng. Sci., 2015, 131: 219-234). The percentage of multiple breakage comparing to binary breakup was statistically counted. The results indicated that the dimensionless drop diameter η = d / dmax can be adopted to characterize the proportion of binary breakup. Finally, the breakup rate was experimentally measured and the breakup probability was calculated using the inverse method.

While evapotranspiration (ET) is normally measured as one hydrologic component, evaporation (E) and transpiration (T) result from different physical-biological processes. In the two-source model, a trapezoidal framework has been widely applied in recent years. The key to applying the trapezoidal framework is the determination of the dry/wet boundaries of the land surface temperature-vegetation coverage trapezoid (LST-fc). Although algorithms have been developed to characterize the two boundaries, , there still, however, exists a significant uncertainty near the wet boundary which scatters in a discrete and uneven manner. It thus is difficult to precisely locate the wet boundary. To tackle the problem, a Wet Boundary Algorithm (WBA) was developed in this study and the algorithm was applied in the region of Huang-Huai-Hai plain of China by using Pixel Component Arranging and Comparing Algorithm (PCACA) to retrieve ET from MODIS Data. The latent heat flux (LE) observed by eddy covariance (EC) measurements from China FLUXNET was used to verify the modified model where the coefficient of determination (R2) was found to 0.81 and the root-mean-square-error (RMSE) was 22.8 W/m2. The ratio of transpiration to evapotranspiration (T/ET) varied between 0.5-0.75 over the region of Huang-Huai-Hai plain. The spatial and temporal distribution of ET revealed that agriculture practices had a great influence on the hydrological cycle.

Low-cycle fatigue testing of a lead-free solder (InnoLot) based on Sn-3.8Ag-0.7Cu (SAC387) with three simultaneous additions of bismuth, nickel and antimony was conducted using miniature-sized fatigue specimens at different temperatures and strain amplitudes. The experiments show a decline of the load capacity of the solder alloy with the number of loading cycles. The fatigue life of the solder is also decreased by the level of imposed temperature. The modified Coffin-Manson and Morrow models were used to analyze the behavior under fatigue and predict lifetime. The parameters in the two fatigue models which were determined by considering different temperatures and total strain amplitudes. Compared to other reference lead-free solders, the InnoLot solder shows much better fatigue strength. The better fatigue strength is found to result from the effect of BiNiSb elements. Also, lifetime predictions were made with both models for the solder alloy under different conditions.

We study the existence of global bounded smooth solutions to the one-dimensional nonisentropic Euler system with large initial data. We find a sufficient condition on the initial data to obtain the existence of global bounded classical solution to the Cauchy problem.

Studying spread of epidemics and diseases are world wide problems especially during the current time where the whole world is suffering from COVID-19 pandemic. Antimicrobial resistance (AMR) and waning vaccination are classified as world wide problems. Both depend on the exposure time to antibiotic and vaccination. Here, a simple model for competition between drug resistant and drug sensitive bacteria is given. Conditions for local stability are investigated which agree with observation. Existence of positive solution in the AMR complex networks is proved. Dynamics of the identical AMR models are explored with different topologies of complex networks such as global, star, line and unidirectional line networks coupled through their susceptible states. Chaotic attractors are shown to be existed as the AMR models are located on all the indicted topologies of complex networks. Thus, it is found that the dynamics of the AMR model become more complicated as it is located on either integer-order or fractional-order complex networks. Furthermore, a discretized version of the fractional AMR model is presented. Complex dynamics such as existence of Neimark–Sacker, flip bifurcations, coexistence of multi attractors, homoclinic connections and multi closed invariant curves are investigated. Basin sets of attraction are also computed. Finally, the discretized system is located on complex networks with different topologies which also show rich variety of complex dynamics. Also, 0-1 test is used to verify the existence of unpredictable dynamics. So, studying the dynamics of AMR models on complex networks is very helpful to understand the mechanism of spread of diseases.

Purpose:There have been concerted efforts towards cataloging rare and deleterious variants in different world population using high throughput genotyping and sequencing based methods. The Indian populations are underrepresented or its information w.r.t. clinically relevant variants are sparse in public datasets. The aim of this study was to estimate the burden of monogenic disease causing variants in Indian populations. Towards this, we have assessed the frequency profile of monogenic phenotype associated ClinVar variants. Methods: The study utilized genotype dataset (global-screening-array, Illumina) from 2795 individuals (multiple in-house genomics cohorts) representing diverse ethnic and geographically distinct Indian populations. Results: Of the analyzed variants from GSA, ~12% were found to be informative and were either not known earlier or underrepresented in public databases in terms of their frequencies. These variants were linked to disorders, viz. Inborn-errors of Metabolism, Monogenic-diabetes, hereditary cancers and various other hereditary conditions. We have also shown that our study cohort is genetically better representatives of Indian populations than its representation in1000 genome project (South-Asians). Conclusion: We have created a database, ClinIndb [(http://clinindb.igib.res.in) and (https://databases.lovd.nl/shared/variants?search_owned_by_=%3D%22Mohamed%20Faruq%22)], to help clinicians and researchers in diagnosis, counseling and development of appropriate genetic screening tools relevant to the Indian populations and Indians living abroad.

Holoprosencephaly (HPE) is the most common congenital anomaly affecting the forebrain and face in humans and occurs as frequently as 1:250 conceptions or 1:10,000 livebirths. Sonic hedgehog (SHH) is one of the best characterized HPE genes that plays crucial roles in numerous developmental processes including midline neural patterning and craniofacial development. The Frizzled class G-Protein Coupled Receptor (GPCR) SMOOTHENED (SMO), whose signalling activity is tightly regulated, is the sole obligate transducer of hedgehog-related signals. However, except for previous reports of somatic oncogenic driver mutations in human cancers (or mosaic tumors in rare syndromes), any potential disease-related role of SMO genetic variation in humans is largely unknown. To our knowledge, ours is the first report of a human hypomorphic variant revealed by functional testing of seven distinct non-synonymous SMO variants derived from HPE molecular and clinical data. Here we describe several zebrafish bioassays developed and guided by a systems biology analysis. This analysis strategy, and detection of hypomorphic variation in human SMO, demonstrates the necessity of integrating the genomic variant findings in HPE probands with other components of the hedgehog gene regulatory network (GRN) in overall medical interpretations.

Conservation agriculture (CA) systems represent a set of three soil management principles that include minimal soil disturbance, permanent soil cover and crop rotations whereas the CA-based systems in this study add the bed and furrow tillage structures as integral elements of CA. This study aimed at investigating the long-term (2005-2013) influence of CA-based systems on soil health and crop productivity in northern Ethiopia. The treatments include two types of CA-based systems (permanent raised bed PRB and contour furrowing CF) and conventional tillage (CT). The experimental layout was arranged in a randomized complete block design. Soil samples were collected at 0-10 cm soil depth to assess soil health. Wheat root samples were used to measure arbuscular mycorrhizal fungi (AMF) colonization percentage using grid line intersect method. Piecewise structural equation modeling (PSEM) was used to understand linkages between management practices, soil health and crop productivity. Higher soil microbial biomass carbon (SMBC), AMF spore abundance and root colonization were recorded in PRB followed by CF as compared to CT (P < 0.05). Carbon sequestration rate, nutrient availability, plant available water capacity and air capacity were significantly higher in PRB and CF compared to CT. Outputs of the PSEM highlighted two pathways in which CA-based systems contributed to improved productivity: (1) via higher density of bacteria and improved hydraulic conductivity, and (2) via higher density of fungi and increase soil organic carbon content in the topsoil. The study concludes that CA-based systems have the potential to improve crop productivity through improved soil health.