Category: 8. Health

Australian researchers have visualized a key protein complex in malaria parasites for the first time, uncovering a new target for next-generation vaccines that could help stop the disease from spreading.

Using cutting-edge cryo-electron microscopy, the research team from WEHI captured the first detailed structure of a protein complex essential for malaria parasite fertilization.

The discovery published in Science has led to the development of a promising new mRNA vaccine candidate that stops the malaria parasite from reproducing inside mosquitoes, breaking the cycle of transmission before it can reach humans.

Malaria remains one of the world’s deadliest infectious diseases, responsible for more than 600,000 deaths each year.

At a glance

• WEHI scientists captured the first high-resolution structure of a key protein complex that’s essential for the malaria parasite to reproduce inside mosquitoes.
• They discovered two small domains of the Pfs230-Pfs48/45 fertilisation complex that are crucial for the parasite’s ability to fertilise and spread.
• A new mRNA vaccine induced antibodies targeting these domains which stopped the parasite from reproducing in mosquitoes, cutting transmission by up to 99.7%.

Visualizing malaria’s reproductive machinery

For many years scientists have known that two key proteins that appear on the surface of the malaria parasite, Pfs230 and Pfs48/45, are important for transmission of the disease.

Lead researcher Dr. Melanie Dietrich said the new study revealed for the first time how these proteins interact – revealing a new vaccine target.

Our structural biology approach was the key. Using cryo-electron microscopy, we were able to visualise the full fertilization complex directly from the parasite – not a lab-made version.

This gave us a clear picture of how this fertilisation complex really looks in nature, and revealed a previously unknown region that’s crucial to the process, unlocking a powerful new vaccine target.”

Dr. Melanie Dietrich, a WEHI postdoctoral fellow, lead researcher 

Lead researcher Professor Wai-Hong Tham said that by capturing the fertilisation complex directly from the parasite, the team revealed the precise contact points that make transmission possible.

“We used these findings to develop a vaccine that showed great promise in targeting these contact points,” Prof Tham, a WEHI laboratory head, said.

“To eliminate malaria, we need to stop transmission. This vaccine candidate could be one piece of that puzzle.”

From structural insight to vaccine innovation

Unlike many structural biology studies that rely on proteins made in the lab from bacterial, insect or mammalian cells, the new research successfully purified the fertilisation complex directly from malaria parasites – a technically challenging approach that ensures the structure reflects its true biological form.

The research revealed the critical contact points for binding the Pfs230 and Pfs48/45 proteins. When these were removed in genetically modified parasites, fertilisation failed and transmission was blocked, illuminating a new vaccine target.

Building on the structural discovery, the team designed a next generation mRNA vaccine which was formulated in collaboration with the mRNA Core facility at the Monash Institute of Pharmaceutical Sciences (MIPS).

In preclinical studies, the vaccine triggered high levels of antibodies that recognised the parasite and blocked transmission in mosquitoes by up to 99.7%.

Professor Colin Pouton from MIPS said it was an exciting opportunity for his team to leverage their expertise in mRNA vaccine development to address an important new target for malaria vaccination.

“Drawing on experience through mRNA Core, the MIPS team shifted focus to tackle a new challenge in malaria vaccination,” Prof Pouton said.

“The success of the malaria vaccine program illustrates the versatility of mRNA technology, which has many applications beyond the COVID vaccines. It was particularly rewarding to work on this project with the WEHI team, co-located in the Parkville precinct, where shared expertise has helped drive a new approach to malaria prevention.”

A vulnerable stage in the parasite’s life cycle

Targeting the parasite inside the mosquito offers a strategic advantage due to what researchers call a population bottleneck.

While malaria parasites are abundant in the human host, only a small fraction develop into sexual forms and are successfully fertilised inside the mosquito. This bottleneck means that even modest reductions in parasite numbers at this stage can have a significant impact on transmission.

Transmission-blocking vaccines – like the one designed through this research, targeting the malaria parasite inside the mosquito – offer a strategic way to halt the spread of malaria, where its numbers are lowest and its life cycle most vulnerable.

Multi-stage strategy towards elimination

The team envisions the mRNA vaccine as part of a multi-stage strategy, targeting the parasite in both the mosquito and human host.

By combining transmission-blocking vaccines with those that act on blood or liver stages in people, researchers hope to build a comprehensive defence that could dramatically reduce malaria burden and move closer to elimination.

Prof Tham said the collaboration between WEHI and MIPS highlighted the strength of the Melbourne Biomedical Precinct and the potential of mRNA technology to rapidly translate basic science into vaccine innovation.

“The ability to design, formulate and test vaccine candidates within a single research ecosystem has accelerated the path from discovery to preclinical validation,” she said.

Oxaliplatin-based adjuvant chemotherapy was associated with significantly improved survival but only in patients with colorectal cancer (CRC) aged 70 years or younger with stage III disease, according to one study.¹ No survival benefit was observed in patients aged more than 70 years or in those with stage II disease, and older patients receiving oxaliplatin were more likely to discontinue treatment.

Oxaliplatin use in older adults with CRC remains controversial.² Although adjuvant chemotherapy has improved outcomes overall, the benefits of adding oxaliplatin for patients aged 70 years and older are uncertain. Although some pooled trial analyses suggest survival benefits regardless of age, these come with increased toxicity, and the survival advantage appears diminished in older patients.

This population-based, retrospective cohort study is published in JAMA Network Open.¹

“This study found no association of oxaliplatin use with improved survival in patients older than 70 years,” wrote the researchers of the study. “This highlights the importance of refining age thresholds and incorporating geriatric assessments into treatment planning to identify patients who are likely to benefit from aggressive regimens.”

The researchers used data from the Korea Health Insurance Review and Assessment Service to examine outcomes among patients with stage II to III CRC who underwent curative surgery and received adjuvant chemotherapy between January 2014 and December 2016. Patients were followed until death or April 30, 2024. Researchers compared overall survival between those who received oxaliplatin-based chemotherapy and those treated with fluoropyrimidine alone.

To determine the optimal age cutoff for oxaliplatin benefit, age thresholds from 60 to 80 years were assessed. Additionally, the researchers evaluated the association between oxaliplatin use and chemotherapy discontinuation across age groups.

Among 8561 patients included in the study, 5648 (65.9%) had stage III CRC and 2913 (34.0%) had stage II disease. In patients with stage II cancer, oxaliplatin use was not associated with improved survival at any age threshold, with adjusted HRs (AHRs) ranging from 0.71 (95% CI, 0.34-1.50) to 1.09 (95% CI, 0.73-1.64). In contrast, for patients with stage III disease aged 70 years or younger, oxaliplatin was linked to significantly improved survival (AHR, 0.59; 95% CI, 0.4-0.77; P < .001), with a 5-year overall survival rate of 84.8% in the oxaliplatin group vs 78.1% in the nonoxaliplatin group (P = .003).

However, among those older than 70 years, oxaliplatin was not associated with improved survival (AHR, 0.85; 95% CI, 0.67-1.07; P = .18) and was linked to a higher risk of chemotherapy discontinuation (adjusted OR, 1.55; 95% CI, 1.19-2.03; P = .001).

However, the researchers acknowledged several limitations to the study, including potential selection bias and incomplete data. Additionally, a lower proportion of younger patients received nonoxaliplatin therapy, which may have affected results despite matching. The analysis also lacked molecular data, recurrence-free survival, and adverse event reporting, limiting insights into treatment tolerability, especially for older adults.

Despite these limitations, the researchers believe the study suggests an age cutoff of 70 years for oxaliplatin therapy among patients with stage III CRC.

“In patients with stage II disease, the lack of association between oxaliplatin and improved survival highlights the need for refined risk stratification to guide adjuvant therapy decisions,” wrote the researchers of the study. “Future research should continue to explore innovative approaches to optimize the treatment of older patients with colorectal cancer to ensure a balance between efficacy and safety.”

References

1. Bong JW, Lee H, Jeong S, et al. Older age threshold for oxaliplatin benefit in stage II to III colorectal cancer. JAMA Netw Open. 2025;8(8):e2525660. doi:10.1001/jamanetworkopen.2025.25660

2. Soveri LM, Lamminmäki A, Hänninen UA, et al. Long-term neuropathy and quality of life in colorectal cancer patients treated with oxaliplatin containing adjuvant chemotherapy. Acta Oncol. 2019;58(4):398-406. doi:10.1080/0284186X.2018.1556804

Hundreds more jobs could be axed at Australia’s national science agency, sparking concerns the country is gutting its research capability just as the Trump administration makes deep cuts into the sector in the US.

The latest potential research job losses at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) follow 440 positions being cut last financial year and earlier deep reductions under the Coalition government, including 300 in 2016.

They coincide with the Trump administration slashing science agencies in the US, with warnings the loss of expertise could have global ramifications in health, climate science and weather forecasting.

The Community and Public Sector Union said the Australian cuts were at odds with the Albanese government’s promise to prioritise economic productivity and urged the government to instead increase investment in the CSIRO.

Susan Tonks, the union’s CSIRO spokesperson, said: “There’s a clear disconnect between the government’s talk about boosting productivity and their failure to support the very institution that helps deliver it.”

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A CSIRO spokesperson confirmed the agency was “reshaping its research portfolio” with a goal of making it more financially sustainable, but did not indicate how many jobs might be lost. They said the changes were in part due to the end of Covid-19 “safety net” funding and other government savings measures, and would “ensure we are focused on delivering the science Australia needs now and into the future”.

David Karoly, a University of Melbourne emeritus professor who previously worked at CSIRO, said the cuts were not being offset elsewhere. He said Australia had lower levels of industry funding in research than comparable countries.

“There’s a dilemma as to whether Australia wants to support the research infrastructure that’s needed to support ongoing research activities in science,” he said. “The simple answer is Australia doesn’t appear to want to do that.”

The latest cuts were understood to primarily affect the CSIRO’s agriculture and food research unit, with reductions in health and safety, IT and business development. Research unit staff were expected to be informed about funding and staffing changes by October.

The May federal budget papers showed an expected 450 person reduction in CSIRO staff, from 5,945 in 2024-25 to 5,495 this financial year.

The union said the cuts were the worst since 2014, when the Abbott government oversaw an estimated 20% reduction in staff.

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Tonks said the agency’s staff were experiencing “deep anxiety” over the CSIRO’s strategic direction and the cuts were “directly undermining Australia’s ability to innovate, compete and grow”.

“This will continue to be the case as long as this government sits on its hands while hundreds of staff at the CSIRO are shown the door with little to no explanation,” she said. “If this government is serious about productivity, it must step in, stop the cuts, and back our country’s peak science institution.”

The CSIRO also confirmed it would sell its stake in the Indian Ocean Marine Research Centre, in Perth’s northern suburbs, by the end of 2025. The agency said it was a “small partner”, owning about 15% of the Watermans Bay site.

A spokesperson said the agency remained “committed to the Indian Ocean Marine Research Centre partnership”.

Type 2 diabetes (T2D) is a global metabolic epidemic driven by insulin resistance (IR), chronic inflammation, and β-cell failure. This review synthesizes evidence establishing immune aging-characterized by thymic involution, inflammaging, and immunosenescence-as a critical accelerator of T2D pathogenesis, particularly in aging populations. Central to this nexus is the “ominous octet” framework, which delineates eight interdependent organ dysfunctions perpetuating hyperglycemia. Here, we elucidate how immune aging intersects with cellular stress pathways to disrupt this network, offering novel targets for intervention.

Key mechanisms linking immune aging and T2D

1. Inflammaging and metabolic dysregulation:
   
   Aging triggers chronic low-grade inflammation via senescence-associated secretory phenotype (SASP), releasing pro-inflammatory cytokines (IL-6, TNF-α). This “inflammaging” impairs insulin signaling, exacerbates IR, and induces β-cell apoptosis through oxidative stress and ER dysfunction. Macrophage polarization shifts from anti-inflammatory (M2) to pro-inflammatory (M1) phenotypes, further disrupting metabolic homeostasis.

2. Hyperinsulinemia-inflammation axis:
   
   Compensatory hyperinsulinemia-initially adaptive-evolves into a pathological driver. Elevated insulin activates stress kinases (JNK, NF-κB), promoting serine phosphorylation of insulin receptor substrates (IRS) and impairing glucose uptake. This fuels a self-propagating cycle: hyperinsulinemia begets inflammation, which worsens IR and β-cell exhaustion.

3. Organelle dysfunction as a unifying pathway:

   
   

   • Mitochondrial dysfunction (MD): Reduces ATP synthesis, elevates ROS, and disrupts calcium signaling, impairing insulin secretion and promoting hepatocyte gluconeogenesis.

   • ER stress: Misfolded proteins activate the unfolded protein response (UPR), inhibiting insulin receptor trafficking and GLUT4 translocation. Persistent ER stress triggers β-cell apoptosis via JNK/NF-κB pathways.
     
     These dysfunctions amplify all components of the ominous octet, creating a metabolic-inflammatory vortex.

     
     
     

Impact on the “ominous octet”

The review details how immune aging and organelle stress exacerbate each element of the octet:

• β-cell failure: AGE-RAGE axis and SASP induce inflammasome activation (NLRP3), accelerating β-cell senescence.

• Hepatic glucose overproduction: Inflammation and MD dysregulate PEPCK/G6Pase, increasing gluconeogenesis.

• Adipose tissue (AT) lipolysis: FFAs from inflamed AT promote ceramide accumulation, activating TLRs and NF-κB.

• Muscle glucose uptake: ROS and ER stress inhibit GLUT4 translocation.

• Renal glucose reabsorption: ER stress upregulates SGLT2 expression.

• Incretin deficiency: GLP-1 secretion is impaired by β-cell ER stress.

  
  

• Neurotransmitter dysregulation: Hypothalamic mitochondrial-ER crosstalk disruption alters appetite control.

Therapeutic implications and future directions

The review advocates multi-targeted strategies to break the immune-metabolic cycle:

• Immunomodulation: Senolytics (e.g., dasatinib/quercetin) clear senescent cells; SPMs (e.g., Resolvin D1) resolve inflammation; GLP-1 RAs promote M2 polarization.

• Organelle protection: Enhancing mitophagy (e.g., spermidine), UPR regulators (e.g., 4-phenylbutyrate), and MAM stabilizers (e.g., mitofusin-2 agonists) restore cellular homeostasis.

• Personalized approaches: Biomarkers like CRP, IL-6, and serine-phosphorylated IRS-1 could guide therapies targeting specific immune-metabolic nodes.
  
  Future research must address clinical heterogeneity (age, ethnicity) and explore emerging areas: gut-microbiome-immune crosstalk, circadian disruption, and α-to-β cell transdifferentiation.

Conclusion

Immune aging is not merely a bystander but a catalytic force in T2D progression. By integrating the ominous octet with immunometabolic stress pathways, this review provides a roadmap for mechanism-based therapeutics aimed at preserving β-cell function and immune resilience in aging populations.

Using portable high-efficiency particulate air purifiers at home can significantly lower systolic blood pressure in adults with elevated baseline readings — even in areas with relatively low overall air pollution levels, according to a study published August 6 in JACC, the flagship journal of the American College of Cardiology.

Particulate matter is a major contributor to air pollution and is strongly associated with cardiovascular disease. People living near high-traffic roadways are frequently exposed to elevated levels of particle matter from vehicle emissions as well as tire and brake wear. These fine particles can infiltrate homes and affect residents, increasing the risk of hypertension and elevated blood pressure – both major cardiovascular disease risk factors.

“High blood pressure remains one of the most important modifiable risk factors for cardiovascular disease,” said lead author of the study Douglas Brugge, professor and chair of the Department of Public Health Sciences at the UConn School of Medicine and UConn Health. “This research adds to growing evidence that simple interventions, like in-home air filtration, may help improve heart health for people at risk.”

In this randomized crossover trial of 154 adults living near highways, participants were randomly assigned to receive one month of either high-efficiency particulate air purifiers or sham filtration (the same units with the filter removed) in their homes, followed by a one-month washout period with no filtration and then the alternate treatment. Blood pressure measurements and participant questionnaires were collected at the start and end of each period.

Researchers found that participants with elevated systolic blood pressure (more than 120 millimeters of mercury) experienced an average 2.8 millimeters of mercury reduction in after one month of filtration. In comparison, systolic blood pressure increased slightly (0.2) during a sham filtration period, resulting in a significant 3.0 difference in favor of filtration. There was no significant impact on diastolic blood pressure or among participants with normal systolic blood pressure.

“Overwhelming evidence shows the harmful health effects of PM2.5 exposure, even at levels below current U.S. standards,” said Dr. Jonathan Newman, associate professor in the Department of Medicine at the Leon H. Charney Division of Cardiology at the New York University Grossman School of Medicine, and lead author of the accompanying editorial comment. “As healthcare professionals, we must educate the public and support policies that protect clean air and improve the health of all Americans.”

Dr. Harlan M. Krumholz, editor-in-chief of JACC, noted that the study raises the possibility that even modest improvements in indoor air quality could have a meaningful impact on blood pressure for people at risk.

“While more research is needed, these results suggest that what we breathe at home may matter for our cardiovascular health,” Krumholz said.

Study limitations include limited generalizability due to a predominantly white, higher-income participant pool, exclusion of people on blood pressure medications, potential variation in purifier use and a lack of data during hotter summer months or at times of higher indoor pollution.

By understanding differences in how people’s brains are wired, clinicians may be able to predict who would benefit from a self-guided anxiety care app, according to a new analysis from a clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian investigators.

The preliminary study suggested that young people with weaker connections between two brain areas involved in both attending to and regulating responses to anxiety were more likely to benefit from a self-guided anxiety care app than those with stronger connections.

The study, published July 31 in JAMA Network Open, looked at data from a subset of clinical trial participants who agreed to undergo a brain MRI before using the anxiety care app developed by the investigators. The app, called Maya, is essentially a course in cognitive behavioral therapy, a gold standard psychotherapeutic intervention that provides users with skills to support them in shifting their thinking, completing challenging behaviors and learning new ways to cope. The interactive platform guides young adults with anxiety through videos, exercises and educational content.

Initial results of the clinical trial with 59 participants showed that using the app reduced anxiety symptoms for many patients; now the new analysis may help identify which patients benefit most. “People with weaker connections in key brain networks involved in anxiety and regulating emotions were more likely to see improved anxiety symptoms with the use of the app,” said senior author Faith Gunning, associate professor of psychology and vice chair for research in the Department of Psychiatry at Weill Cornell Medicine. “That makes sense, because cognitive behavioral therapy helps teach people how to regulate their responses to emotions.”

Gunning and her colleagues developed the Maya app to help fill critical gaps in access to care for young adults with anxiety. Young adults between the ages of 18 and 25 are at a stage in life where they are experiencing many life changes, and studies have shown they are at fairly high risk for anxiety disorders. During this time, they may also have gaps in health care coverage or may have difficulties accessing or affording in-person mental health care. Some may also be hesitant to seek in-person care because of stigma surrounding mental health or because of their anxiety symptoms.

For the clinical trial, 59 young adults with anxiety used the app twice a week for six weeks. Investigators tracked participants’ symptoms during that time and for an additional six weeks. Those who used the app experienced reduced anxiety symptoms throughout the 12-week monitoring period. Some continued to use the app after the initial 6-week trial period, and others experienced lasting improvements in symptoms even after discontinuing use of the app after 6 weeks.

The investigators were able to use data from 30 participants who had MRIs before using the Maya app to determine if specific patterns of brain activity indicated individuals who were more likely to experience symptom improvements.

The results suggest that young adults experiencing anxiety whose brains were less efficient at regulating their responses to anxiety-provoking information benefited more from learning cognitive behavioral therapy techniques through the app. In contrast, those with stronger connections in circuits involved with greater attention to potentially threatening or anxiety provoking information were less likely to benefit from using the app.

“App-based interventions like Maya are poised to address a critical barrier to care for people with anxiety, but like any mental health treatment, some people will benefit more than others,” said first author Abhishek Jaywant, assistant professor of neuropsychology in the Department of Psychiatry at Weill Cornell Medicine and a psychologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Our study is among the first to suggest that patterns of brain function are relevant in helping researchers and clinicians understand response to app-based treatments for anxiety. These findings could one day help us to recommend an app like Maya to patients most likely to benefit.”

“Our study will help us better tailor treatments to patients in the future,” said Gunning, who is also a psychologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Anxiety symptoms can be very disabling to young adults at an important life stage, so matching them with an effective therapy as soon as possible is important.”

This study was supported in part by the National Center for Advancing Translational Sciences and the National Institute of Mental Health, both part of the National Institutes of Health, the NewYork-Presbyterian Center for Youth Mental Health, the Khoury Foundation, the Paul and Jenna Segal Family Foundation, the Saks Fifth Avenue Foundation, Mary and Jonathan Rather, the Weill Cornell Medicine Children’s Health Investigator’s Fund, and the Pritzker Neuropsychiatric Disorders Research Consortium.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see profiles for Faith Gunning and Abhishek Jaywant.

Bridget Kuehn is a freelance writer for Weill Cornell Medicine.

The plant pathogen Pseudomonas syringae pv. actinidiae, or Psa, causes kiwifruit canker and contributes to larger issues of food shortage. Finding biocontrol agents that specifically target this pathogen would benefit agricultural production. Endolysin enzymes from bacteriophages have emerged as promising candidates. Endolysins cleave peptidoglycan, a layer of the cell wall in gram-positive bacteria. However, the gram-negative Psa has an outer membrane that shields the peptidoglycan inner layer. Suzanne Warring and Hazel Sisson at the University of Otago and a team of international scientists recently published their research in the Journal of Biological Chemistry on developing an endolysin fusion protein active against Psa.

The authors used VersaTile molecular shuffling, a technique that created a library of phage proteins attached to endolysin. They performed a high-throughput screen for peptidoglycan-degrading activity and identified a lead compound that inhibited Psa growth. This hit compound, called ELP-E10, contains a lipase fused to endolysin, and the authors determined that the antibacterial activity relies on functional active sites for each fusion partner.

Notably, ELP-E10 shows specific activity for Psa, especially when combined with citric acid as a chemical permeabilizer. The researchers tested ELP-E10 activity against pathogens Pseudomonas aeruginosa and Staphylococcus aureus, as well as the commensal soil bacteria Pseudomonas fluorescens, and found that ELP-E10 shows specificity for Psa.

More experiments will help determine the exact outer membrane substrate that the lipase of ELP-E10 targets to allow the endolysin to reach the Psa peptidoglycan. These results suggest that endolysin fusion proteins could form promising antimicrobial candidates for agricultural use.

The addition of blood tests for two biomarkers improves the accuracy of a test used to decide whether people with an irregular heartbeat, known as atrial fibrillation, need to take anticoagulant medication to reduce their risk for stroke.

“Stroke risk scores, such as the guideline-recommended CHA₂DS₂-VASc score, are widely used to assist decision making for anticoagulation in atrial fibrillation,” write lead author Mary Cushman, MD, a professor at the University of Vermont, and colleagues in the Journal of Thrombosis and Haemostasis.

“While this approach has transformed clinical practice, the decision to recommend anticoagulation to patients with atrial fibrillation remains difficult as current risk tools have substantial limitations.”

The researchers set out to discover if adding certain biomarker blood tests to medical assessment of patients with atrial fibrillation could better predict their risk for future stroke.

The study assessed people who developed stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Of 30,239 participants, 2411 had atrial fibrillation and 163 developed stroke over a period of 13 years.

Overall, nine biomarker tests were carried out and assessed, with additional supporting results published in a linked study published concurrently in the same journal. Higher levels of the biomarkers N-terminal pro-B-type natriuretic peptide, growth differentiation factor 15, cystatin C, interleukin 6, and lipoprotein(a) were all linked with higher stroke risk after adjusting for confounding factors.

The researchers also assessed whether they could use their results to improve the accuracy of the existing CHA₂DS₂-VASc score. They found that adding the biomarkers N-terminal pro-B-type natriuretic peptide and growth differentiation factor 15 to the model led to the best results and they released a link to a new online CHA₂DS₂-VASc Biomarkers calculator.

“This could be a game-changer for stroke prevention,” said Cushman in a press statement. “We’re giving physicians a sharper tool to provide a personalized approach to anticoagulation for patients who need it most, while sparing others from unnecessary risk.”