Blood transfusions are extremely important, and potentially life-saving medical procedures. Though not highly common, transfusion errors can have fatal consequences. A recent study tracking hospital transfusions from 2005 to 2010 found that 60 percent of errors occurred during the actual transfusion, while the remaining 40 percent occurred in clinical services (handling, labeling, and transportation of samples). The two most common mistakes identified in the study were sample labeling and inappropriate ordering of blood. Complications may occur as early as during the transfusion or as delayed as months or years later.
- Febrile Transfusion Reaction – This complication typically occurs shortly after the transfusion begins. The patient experiences an accelerated fever spike, accompanied by chills, shaking, increased blood pressure, increased respiration, anxiety, and headache.
- Acute Hemolytic Transfusion Reaction (AHTR) – This occurs when the wrong blood type is transfused. The recipient’s body rejects and then attacks the red blood cells of the incompatible donated blood. As the donated blood cells die, they release a substance harmful to the kidneys. This process happens quickly after the start of the transfusion, with symptoms including low back and chest pain, nausea, fever, and chills. AHTR is potentially life-threatening.
- Delayed Hemolytic Transfusion Reaction (DHTR) – Like acute hemolytic transfusion reaction, DHTR occurs when the wrong blood type is transfused into the recipient’s system. However, with DHTR, the rejection and attack on the donor cells happen gradually, generally taking one to four weeks to cause symptoms.
- Transfusion-related Lung Injury (TRALI) – Not fully understood by medical experts, this reaction involves antibodies within the blood and affects the lungs. It can make breathing extremely difficult. TRALI symptoms usually present within one to six hours after the transfusion. Fatalities typically only occur among patients with certain pre-existing conditions.
- Blood-borne infections – Failure to screen properly for contaminated blood may result in blood-borne infections including HIV, hepatitis B and C, West Nile virus, parasites, and bacterial infections. Symptoms of these may not present until weeks or months after the transfusion.
- Iron overload – Multiple transfusions may result in hemochromatosis, or iron overload. This can result in serious damage to the heart and lungs.
While transfusion errors can have numerous causes, the majority of transfusion errors result from mistakes made by doctors, nurses, and other medical professionals. If you contract an illness or suffer a harmful medical condition as a result of a mistake made during your procedure, you may have a claim for medical malpractice. Some of the more common examples of mistakes that can give rise to malpractice claims include:
- Blood contamination resulting from improper storage.
- Failing to follow transfusion protocols, which can lead to clotting or cause bubbles to form in the blood.
- Improper labeling or misreading of labels, resulting in administration of the wrong blood type.
- Improper screening, resulting in transfusion of contaminated blood.
- Patient misidentification.
- Performance of unnecessary blood transfusions.
- Other procedural and administrative errors resulting in administration of the wrong blood type or contaminated blood.
Berkowitz and Hanna LLC – Medical Malpractice Attorneys
Medical conditions resulting from blood transfusion errors can result in serious, debilitating, and life-threatening medical issues. If you have experienced pain and suffering, incurred medical expenses, or missed time from work due to a blood transfusion error, contacting a medical malpractice attorney may be in your best interests.
At Berkowitz and Hanna LLC, we have over 40 years of experience helping clients obtain financial compensation for medical malpractice. Our attorneys have extensive experience in the field, with a seasoned understanding of how to effectively pursue claims maximum compensation. To find out if you may have a claim for medical malpractice as a result of a blood transfusion error, contact Berkowitz and Hanna LLC today for a free consultation. We will be by your side every step of the way.


The concept of this work is the question of presenting today’s educational system through the eyes of children. I wonder as to how and where the pupils experience and practice in everyday life the following educational achievements: appropriateness, regularity, vigorous proof, restriction, appointment keeping, empowerment?
In the performance, I instruct the audience to read the Pupils’ Rights from the Act on Education in Primary Schools of the Republic of Croatia.
I repeat the statements after audience members, all the while tightening a bushy branch around my neck. When the audience are done reading the seven rights of pupils, I tell them to invent a new right based on their experience at school, be it good or bad. Afterwards, as materialised memory of that moment, I give out corn seeds to the audience, to be planted somewhere in the yard of the Cultural Centre of Peščenica (Zagreb).
- * the right to be informed of all matters pertaining to them.
- * the right to counselling and assistance in solving the problem in accordance with their best interests.
- * the right to have their opinion respected.
- * the right to assist other pupils at school.
- * the right to make a complaint that can be referred to teachers, the Director, and the School Board.
- * the right to participate in the work of the School Council of Pupils.
- * the right to suggest improvements in the educational process and work.


Learn How to become a good fashion designer
According to a dictionary, the word “fashion” has two meanings one is (noun) “a popular or the latest style of clothing, hair, decoration or behaviour.” And other is (verb) “to make into something”. There are three important phrases in these definitions latest or new, style and make into something. So there are two aspects underlined by the definition. One is style and the second one is someone who creates that style.
Simply put, fashion is an art of transforming a simple looking attire into an elegant one. It refers to a style or practice, especially in clothing, footwear, accessories, makeup, or furniture. The genius who creates that style is a fashion designer.
A fashion designer is responsible for the creation of new designs that aim to set a trend. He/she creates designs for new clothing and accessories. A fashion designer has to keep track of the latest trends, analyze them and come up with a unique piece of design. His work does not stop at the design. He has to convert his idea into reality, into a garment or accessories by taking help of various departments like production, sales, and marketing.
Opportunities for Fashion Designers
Fashion designers can pursue a career at various organizations like a retail store, fashion firms, costume design department etc. If we search on popular job portals, we will find demand for fashion designers from many cities.
Search for “fashion designer” on job portals, you will find around 400to 500 jobs posted as recent as last 30 days
Responsibilities of fashion designer
Let us study some of the job descriptions available on different job portal on the internet. Here are some of the common roles and responsibilities observed on job portals.
- Track latest fashion trends and anticipate new designs.
- Track general trends relating to fabric, colors, and shapes.
- Decide on a theme for launching a collection.
- Creating or visualizing an idea and putting it on paper.
- Select fabrics, embellishments, colors, or a style for each garment or accessory to be produced.
- Use computer software and create fashion designs.
- Work with other designers or team members to create a design prototype.
- Oversee the final production of their designs.
Sometimes, very specific things are mentioned.
- A designer should be able to create & design Men’s Wear Items like T-Shirts, hoodies, Jogger’s Pants with different patterns
- Should be very good in designing ladies wear such as dresses, rompers, and jumpers with multicolor prints
- A designer should be very good in creating new prints of florals, nautical or ethnics in alignment with the current trends
- Need to have good taste for Accessories Designs such as Labels & Hang Tags and Embroidery Designs along with Catalog knowledge.
Word of caution
Though the career in fashion is with all the glamour, it is important for one to remember that it is not easy to become the next celebrity fashion designer. There are very few to achieve this feat.
Expect hard work. When the timelines for the planned events like a fashion show or new launches are near, fashion designers have to work hard for long hours. Fierce competition an aspiring fashion designer has to face as more and more people are drawn to the fashion industry.
One needs to be passionate, creative and well-trained to accomplish the dream of becoming a great fashion designer.
What I have to do to become a Fashion Designer
There are various training programs which can be taken for one to become a fashion designer. These courses cover the history of fashion, sewing, tailoring, pattern making, software like computer-aided design (CAD) and various types of designs in clothing.
As an aspiring fashion designer, who should start tracking and reading about fashion trends to know what the new wave is. Searching for and doing an internship while pursuing education will add a lot of value. Rather it will give you a lot of exposure to real work in the fashion industry.
When you will join the fashion industry it is obvious that you would start working under someone who is more experienced. You would start as a design assistant and then become an assistant designer. After growing in skills and experience you may become a design director or fashion director. Explore Career Path after Fashion Designing Courses in Pune
India is one of the fastest growing economies in the world. Increasing disposable income, exposure to international brands, availability of internet and penetration of smartphones, tech-savvy young millennial are some of the key aspects which are driving the growth of retail industry, especially the fashion brands.
With all its glitz and glamour fashion industry attracts many young minds who aspire to pursue a career here. However, this career is just not for everybody’s cup of tea. It is important to check if you have something in you that can make you successful here.
Skills to become a great fashion designer
Here are some of these critical skills which one needs to acquire to become a great fashion designer. These skills can be grouped into three categories namely design skills, soft skills, and business skills.
They are about the new designs a fashion designer creates.
Creativity is an exceptional ability to see mundane, day to day things in the world with a completely different perspective. It is the ability to connect dots amongst things which appear to be completely unrelated. You happen to come across something and are suddenly inspired to create something, maybe a piece of art, which is out of this world. You see the fabric and are able to imagine a finished product which is completely orthogonal to the current trend, awesome and novel. Creativity is about not only imagining a new thing but also bringing it into a reality. And this is the most coveted skill for a fashion designer.
To turn your imagination into reality, what you need is a strong visualization skill. Just by looking at the fabric or a piece of jewelry, you should be able to visualize the complete finished product, the attire, what piece of jewelry would go with what kind of clothes etc. Stronger the visualization, better is the clarity. This will make your life easy while putting your ideas on paper. Your team would be able to perceive your idea with much clarity as it works towards the complete product.
Understanding Texture, Color, and style
As a designer, you require to have a good sense of texture, color, and style. The sense of color and style are like innate skills, you are born with them. You have an eye to understand that this color goes well with the other color or I should make this fabric 10% darker or lighter to enhance the impact. Similarly, the garment which you are making would look flattering if done in silk or otherwise. With a good sense of color and use of fabric, all famous designers have a great sense of style. This makes their work unique.
Drawing skills and Eye for Detail
Fashion designers need to have a good ability to draw either on paper or with software on using the computer. This will help you put your novel concept on paper. Along with drawing skills, you need to have an eye for detail. The small details only make the product really stand out.
This group includes software aspects like communication and teamwork.
Excellent Communication, Interpersonal Skills, and Teamwork
This is one of the key skills you will need to be a great fashion designer. You may be very creative, great at visualization, but if you are not able to effectively communicate your imagination to your colleagues, it will be extremely difficult to produce in reality what you have imagined. One needs to have excellent communication and interpersonal skills so that the entire team works towards making the designer’s vision a reality. Ability to work with the team and taking the team along are also key traits of a great designer.
Passion and Interest in Current Fashion Trends
You need to be passionate about fashion. The person who is a “fashion buff” would track every event, happening currently in the fashion industry. Ethnic lehenga or short kurtas, what is more, trending and dominating in the current market? Such trends are vital and need to be tracked regularly. This will help you not only become a successful fashion designer but also stay ahead of the competition.
These skills depict good understanding of various aspects like sales, finance, and marketing of a business.
Good Business Sense
Successful fashion designers have a very good understanding of the business. In addition to creativity, they are also good at managing budgets, activities for effective sales and marketing. Without these skills, it is not possible to make the fashion brand sustain and profitable.
Acquiring skills to become a fashion designer with INSD Pune
We have discussed the critical skills needed for one to become a successful fashion designer. Some of these skills are innate but many of them can be acquired under the guidance of good mentors and coaches. Even the innate skills need to be honed and polished so that one is ready to stand confidently in the fiercely competitive market like fashion. Taking admission at INSD Pune will prove to be a great first step in this regard. INSD Pune is committed to enhance and nurture your talents and help you pursue your dream career in this glamorous fashion land.
A career in Fashion Designing
“Jennifer wears a black jersey wrap dress by Simon Armstrong, a classic silhouette that flatters every figure. A snow white necklace, hand-carved mahogany bracelet, — a wardrobe must-have this season — all from Needles and Threads Boutique.”
There is an electrifying excitement in the air, you are watching a fashion show. People enjoy such cutting-edge ensembles in fashion shows. It’s the world of glamour.
What is Fashion?
Fashion is a general term for a popular style or practice, especially in clothing, footwear, accessories, makeup, body piercing, or furniture. It refers to a distinctive and often habitual trend in the style with which a person dresses, as well as to prevailing styles in behaviour.
To put it in simple words, it is basically the style of wearing clothes, accessories, and ornaments according to the ruling trends or one’s own individual preferences. Fashion, in essence, is the art of transforming a simple attire into one that of elegance.
Fashion is an essential part of our life, whether we explicitly see and accept it or not. Every day the choices you make about your looks are all related to fashion. Fashion is important because it helps you step your best foot forward. When you wear good clothes you not only look beautiful but confident too.
The best way to enjoy fashion is to wear what you love and be yourself! Fashion has the ability to transform you into a completely new personality. Fashion is important in society because it allows people to express their personality. Fashion has the potential to bring different people together.
What is beyond this? Love for fashion is love for creativity. If nurtured well can get you a very rewarding and career in this glamorous world.
Careers in the world of Fashion
Let us see what are the career opportunities available today in the fashion industry. Fortunately, fashion being a vast field there are various career options for those creative minds who are willing to pursue the untrodden paths like fashion design. Fashion industry offers numerous career choices. Broadly speaking one can classify fashion industry job opportunities into the following categories as shown below
Skills needed for Career in Fashion Design
Many people start their education dreaming to become engineers, doctors and bank officers, and so on. However, there are many others who want to pursue something different, more creative and inspiring. If you are one from a creative type belonging to the second category, the fashion world is the right place for you. Like every other profession, to pursue and become successful one needs to have certain qualities and skills. Fashion design is no exception.
One needs to be highly creative to pursue a career in fashion design. You should have a great sense of style and ability to come up with new fashion ideas. Coupled with creativity, strong drawing skills are needed so that one can put his/her new ideas on paper. The successful fashion designer has exceptional visualization. They can visualize how the complete garment would look like, even before they have touched their pencil to paper.
Fashion is changing every day. One who is passionate about designing his/her own garments also needs to track what is happening in the world around. Tracking new trends in the fashion world is crucial. One should be good at anticipating what your audience would expect next or be crazy about. Along with all these qualities, good communication and sense of business are also equally important.
Some of these qualities and skills can be inborn, but many of them can be learned under good mentorship and guidance.
How to Become Successful Fashion Designer with INSD Pune
There are many institutes which provide the necessary training through well-planned courses. But it is imperative that you select reputed, acclaimed and well-known institute for pursuing fashion designing. A strong foundation goes long way in developing a successful career in Fashion Designing.
INSD Pune is the institute where you want to take admission as it helps and motivates you to realize your own potential and make your mark in the fashion industry. You get guidance at every step, throughout the duration of your chosen course and then some. You can rest assured that INSD provides 100% placement assistance + Fixed Internship.
Your career as a Fashion Designer gets a massive boost by beginning work at famous brands such as Vogue, Orient Craft, P.C. Chandra to name a few. So lay the foundation of your successful career by taking admission at INSD.


Roles of Human Respiratory Syncytial Virus Proteins in Immune Responses
Fengjie Wang, Linqing Zhao*
Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, P. R. China
*Corresponding author: Prof. Linqing Zhao, Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Chaoyang District, Beijing 100020, P. R. China
Received: 03 March 2021; Accepted: 15 March 2021; Published: 25 March 2021
Citation: Fengjie Wang, Linqing Zhao. Roles of Human Respiratory Syncytial Virus Proteins in Immune Responses. Archives of Clinical and Biomedical Research 5 (2020): 185-200.View / Download Pdf Share at Facebook
Human respiratory syncytial virus (hRSV) has evaded active vaccination or effective antiviral therapy for decades and continues to be the leading cause of morbidity and hospitalization in infants, the elderly, and the immunocompromised worldwide. Inadequate understanding of the antigenic intricacies of its viral proteins and the immune responses they generate in the host is the greatest obstacle to the progress of hRSV prevention and treatment. Currently, the prefusion F protein is considered the most effective antigen for inducing protective immunity. Other molecular components of hRSV, such as the G or N proteins, have also been explored as potential targets for disease control. However, important knowledge gaps remain about the role played by various hRSV proteins in immunobiology and pathology. This review summarizes the unique immunomodulatory aspects of hRSV infection, the viral proteins involved in intracellular immune signaling, and the viral interactions in play with the host’s immune system.
Human respiratory syncytial virus; Virus proteins; Immunobiology; Pathology; Immune signaling; Immune system
Human respiratory syncytial virus (hRSV), the leading cause of acute lower respiratory tract infections (LRTIs) in infants and young children worldwide, is also responsible for severe respiratory disease in the elderly and the immunocompromised. It is estimated that hRSV infections cause the hospitalization of about 3.2 million young children with LRTIs, and about 59,000 children younger than 5 years died from them in 2015 [1, 2]. hRSV infections can cause bronchiolitis and result in chronic lung diseases such as wheezing and asthma in later life [3, 4]. Accumulating data now supports a causal role for hRSV LRTIs in the development of hypertension caused by inflammation around the small vessels in the airways [5, 6]. Although hRSV is a major public health burden, effective prevention and therapeutic measures are lacking. Passive prophylaxis with palivizumab, a humanized anti-F monoclonal antibody (mAb), is restricted to premature infants. Vaccines face multiple issues, such as the low activity of neutralizing antibodies after immunization, or the aggravation of pathological reactions from the imbalance of Th1/Th2 cytokine secretion after formalin inactivated hRSV is administered. The biggest barrier to hRSV prevention and treatment is the multiple gaps in our understanding of the pathogenesis and protective immunity mechanisms underlying hRSV infection. This review summarizes the unique immune-modulatory aspects of hRSV infection that are associated with the roles performed by viral proteins in intracellular immune signaling, their interactions with the host immune system, and their possible implications for disease pathology.
Based on the distinct phylogeny of the polymerase (L) protein and the presence of a conserved M2 gene, both of which are involved in transcriptional regulation and virus morphology, hRSV was renamed human Orthopneumovirus to fit with its taxonomical classification as a member of the Orthopneumovirus genus (Pneumoviridae family) . hRSV is an enveloped virus with a negative-stranded, non-segmented RNA genome containing 10 genes distributed along 15.2 kilobases in the order 3′-NS1-NS2-N-P-M-SH-G-F-M2-L-5′ and encoding 11 proteins . The lipid envelope surrounding the nucleocapsid is derived from the host cell plasma membrane during the budding process. This envelope contains three virally encoded surface transmembrane glycoproteins: G, F, and SH. It has been confirmed that G and F surface glycoproteins can induce protective immunity in animal models and are believed to be the main targets for neutralizing hRSV antibodies. Investigations on the mechanism of hRSV-induced immunopathology have increasingly focused on the G and F proteins, and new therapeutic strategies targeting them have gradually arisen. Based on the antigenic differences in F and G, hRSVs fall into subtypes A and B (hRSV-A and hRSV-B), but the F gene shows sequence conservation between hRSV-A and hRSV-B. HVR1 and HVR2, two highly variable regions present in the extracellular region of the highly variable G glycoprotein, are separated by a highly conserved region of 13 amino acids (positions 163–189). Sequence analysis of the HVRs indicates that there is only 67% (nucleotide level) and 53% similarity (deduced amino acid level) between hRSV-A and hRSV-B, respectively . hRSV A and B subtypes can be divided into a variety of genotypes based on the nucleotide sequences of HVR2.
The virion matrix proteins M1 and M2 are non-glycosylated, and N, P, and L associate with genomic RNA to form the nucleocapsid, whereas two non-structural proteins, NS1 and NS2, are expressed only during cellular infections and are not packaged into the virion . Internal hRSV proteins (e.g., N, M, and M2-1), can induce T cell immunity alone or in combination with surface proteins, and these processes may be important therapeutic targets for regulating immune responses; however, knowledge gaps in this area highlight the need for further research. Nevertheless, the roles played by hRSV proteins in pathogenesis and immunopathology in the host provide clues to their potential contributions to a vaccine.
3. Immune responses and pathology in hRSV infections
The immature infant immune system, the low lymphocyte levels in young children, and the low levels of hRSV-specific neutralizing antibodies in the blood of the elderly and the immunocompromised are the main reasons for the high susceptibility of these people to hRSV. It is important, therefore, to determine how to induce protective antibodies, elicit supportive T helper responses, and invoke sufficient CD8+ T cells to clear the virus in hRSV-susceptible populations. However, the unique immunobiology of infection with hRSV means that obstacles to specific treatments or a safe and effective vaccine remain. The host immune responses to hRSV lack immunological prowess during the primary exposure, and this may leave a suboptimal imprint on the adaptive immune response . Adding to that, neonates tend to have an inherent Th2-biased response that impairs the ability to induce helper T cells and optimal CD8+ T cell responses .
3.1 Innate immune responses
hRSV first invades respiratory epithelial cells through its G and F viral membrane proteins, thereby internalizing the virions and enabling subsequent replication, transcription, and translation of progeny viruses in cells, which can then infect other cells. It has been suggested that hRSV is anchored to respiratory epithelial cells by pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic-acid-inducible gene-I-like receptors or nucleotide binding-oligomerization domain-like receptors , leading to the downstream activation of NF-kB and interferon regulatory factors to regulate the expression of type I and III IFNs, IFN stimulated genes, and pro-inflammatory mediators [14, 15]. The production of these factors can promote the formation and activation of the inflammasome and cell death in some cases, as well as controlling the virus and directing the development of adaptive immune responses .
TLRs are the main extracellular receptors for hRSV recognition. Through its interaction with the F protein present on the viral envelope, the TLR4/CD14 complex provokes an NF-kB-mediated cytokine response, which includes the secretion of interleukin (IL)-8, IL-10, and IL-6 [17, 18]. TLR2 and TLR4 receptor complexes are able to traffic into the endolysosome, from where they can activate the innate immune response. However, TLR2 alone does not contribute to the production of IFN-α and IFN-β . Instead, TLR3 induction activates the innate immune response through the TRIF-mediated pathway to promote the expression of CCL-5, IFN-α, and IFN-β . In addition, TLR3 and TLR7 recognize viral RNA, and their deficiency can change the inflammatory environment in the lungs during hRSV infection, leading to enhanced mucus production and worsened lung epithelial cell hyperplasia, but this does not affect viral clearance [21, 22].
Innate PRR signaling also induces a spectrum of chemokine and cytokine expression (e.g., CXCL3, CXCL5, CXCL8, CXCL9, CXCL10, IL-4, IL-6, IL-11, IL-15 and TNF-α), which is crucial to the initiation of anti-hRSV immune responses by regulating leukocyte infiltration and localization in the lungs, further affecting the balance between pathogenesis and virus elimination [23-25]. In addition to their direct cellular effects on the infection sites, these chemokines and cytokines act as potent chemo-attractants, activating and recruiting circulating immune cells, such as neutrophils, NK cells, and cytotoxic T cells, to the airway mucosa. Otherwise, hRSV infection elicits a strong systemic response, especially in the innate immune cells of the respiratory tract (e.g., neutrophils, natural killer cells, dendritic cells, macrophages, monocytes and eosinophils) to form a critical link between recognition and transportation of the viral stimuli to the draining lymph nodes and activation of cell-mediated antiviral responses, while dendritic cells also provide a critical link between the innate immune response and adaptive immunity induction . Tissue-resident macrophages and intraepithelial dendritic cells continually capture viral particles in the airway lumen and internalize them by phagocytosis and macropinocytosis, thereby activating PRRs and initiating immune responses . These innate immune processes work synergistically to immediately and effectively identify the invading pathogens and orchestrate adaptive immune responses.
3.2 Adaptive immune responses
In the later stage of hRSV infections, virions induce specific adaptive immune responses in hosts, including the production of IgA secretory antibodies by respiratory mucosa cells, IgE by eosinophils, serum IgM and IgG antibodies by B cells and cellular immunity by T cells, all which endow antigenic specificity and diversity of antigen recognition. Evidence shows that the production of hRSV-specific antibodies regulates the T-cell response, indicating that responses mediated by antibodies and T cells are interdependent . Antibody responses in infants mainly targeting F and G glycoproteins show a gradually increasing trend from the acute phase to the convalescent phase during natural primary hRSV infections . With circulating CD5+ and CD19+ B and CD20+ B-cell accumulation, there are higher quantities of IgM, IgG, and IgA plasma cells in the lungs of infants with hRSV bronchiolitis . In children with hRSV bronchiolitis or pneumonia, higher serum IgE levels on hospital admission are reportedly associated with prolonged fever and more serious symptoms . The existing natural hRSV-specific nasal IgA and serum IgG with high neutralizing titers in adults are correlated with protection against naturally acquired reinfection with hRSV .
The T cell response plays a critical role in host defenses against hRSV infection. An appropriate cellular immune response is essential for generating protective antibodies and clearing primary hRSV infection. However, an unbalanced and dysregulated T cell response can cause pathology. In a murine model of hRSV infection, CD4+ T cell production of IL-9, IL-13, and IL-17 contribute to hRSV-induced disease . The types of improper CD4+ T cell responses (e.g., Th2-, Th9-, and Th17-related cytokine induction) observed in hRSV-infected infants, which also induce disease in the mouse model of primary hRSV infection, are also seen in various vaccination settings . CD8+ T cells can control acute viral infections by secreting cytokines and lysing infected host cells, but also can result in marked disease enhancement . In early life, CD8+ T cell depletion leads to enhanced Th-2 responses during hRSV infection, and virion spreading to the mediastinal lymph nodes results in severe and potentially fatal hRSV infections . CD8+ and CD4+ T cells both play roles in terminating hRSV replication, while the Th1 and Th2 balance manages the progression of the response. During the course of hRSV infection, the expansion of CD8+ T cells is greater than that of CD4+ T cells and is accompanied by the release of a series of cytokines and chemokines, imbalanced Th1/Th2-type cytokines, and aggregation of various inflammatory cells, eventually leading to multi-system pathological damage.
4. Roles Played by Viral Proteins in hrsv Infection-Associated Immune Responses and Pathology
4.1 F protein
The F protein, a type I transmembrane glycoprotein, mediates fusion of the viral envelope to cellular membranes and syncytium formation. Its deletion results in a drastic reduction in viral infectivity. It is relatively conserved across all hRSV strains and varies only slightly in its expression pattern. The F protein is highly conserved, and most candidate vaccines and monoclonal antibody drugs are specifically designed to target it. Synthesized as a single inactive polypeptide (F0), its two furin cleavage sites undergo proteolytic cleavage, a process required for membrane fusion activation , which produces two disulfide-linked polypeptides, C-terminal F1 and N-terminal F2. The mature F glycoprotein is a homotrimer of F1 and F2 subunits . The F1 region is immunogenic in that it contains the main epitope of the F protein. In addition to promoting viral–cell membrane fusion, studies have shown that the F protein is also involved in viral attachment via its interaction with several cell surface proteins, such as ICAM-1, TLR4, nucleolin, and the epidermal growth factor receptor (EGFR) [39-42]. When F binds to EGFR, mucin production and the secretion of cytokines such as IL-13 occur; therefore, mutations in key sites of the F protein in a live attenuated hRSV vaccine that blocks F binding to the EGFR should weaken the ability of hRSV to generate a successful infection . In murine, the F protein has been shown to interact with, and subsequently signal through, components of the lipopolysaccharide receptor system . The latest research shows that the interaction between the F glycoprotein and the insulin-like growth factor-1 receptor is the mechanism used for viral entry, a finding that may provide new opportunities for the treatment of hRSV infection .
It has been shown that the hRSV F glycoprotein stimulates innate immunity by activating the parts of the receptor complexes involved in the innate immune response to hRSV; that is, CD14 and TLR4. Activated TLR4 triggers a signaling cascade by activating the NF-κB transcription factor and by activating multiple mediators of innate immunity to secrete cytokines, such as IL-8, IL-10, and IL-6, and by sensitizing airway epithelial cells to endotoxin [46-48]. The F protein is involved in both humoral and cellular immunity, and chemokine release mediated by whole viral particles or the F protein has been shown to initiate neutrophil, CD4+ T cell and eosinophil chemotaxis. Activated Th1 CD4+ T cells can cause changes in the T cell response to infection as well as creating Th1/Th2 cytokine secretion imbalance, which further leads to delayed hypersensitivity in the host and abnormalities in pulmonary function, such as asthma .
The F protein is a major target of the neutralizing antibodies induced by natural infection with hRSV, making it an attractive target for monoclonal antibody development and vaccines. Anti-F antibodies can mediate antibody dependent cell-mediated cytotoxicity (ADCC) in vitro , and this may offer some potential for treating hRSV. Neutralizing antibodies against the F protein can protect against infection by hRSV subtypes A and B. Most neutralizing epitopes are on the prefusion F (pre-F) protein structure, and the stabilized prefusion protein is more immunogenic and protective than the postfusion protein . To date, at least six neutralizing antigenic sites on F (sites I, II, III, IV, V, and Ø) have been identified and antibodies with major neutralizing activities were found to be specific for the pre-F anti-antigenic Ø site . MEDI8897, a highly potent recombinant hRSV mAb optimized from D25 that recognizes the antigenic Ø site on the apex of the pre-F molecule, has opened up new treatment possibilities for hRSV infection in infants .
4.2 G protein
The G membrane protein, a type II putative attachment transmembrane protein embedded in the viral lipid envelope, plays an adhesion function between virions and host cells. In infected cells, hRSV G, which is involved in immune evasion/antagonism, is produced as a full-length membrane-anchored form and a secreted form encoded by an alternative initiation codon in the transmembrane domain . The G protein has highly variable mucin domains at both of its ends, along with a high proline content and extensive O-linked glycosylation surrounding a central conserved domain. Glycosylation changes in G may contribute to hRSV escape from the host’s humoral immune response. The central region of hRSV G contains a CX3C motif that can bind to CX3CR1, which induces leukocyte chemotaxis and may be significant to the biology of hRSV infection and viral pathogenesis.
Accumulating evidence shows that the hRSV G protein has immune modulatory activities. hRSV replication in airway epithelial cells leads to the release of the soluble form of the G-protein, which is involved in the immune modulation process of innate immunity and the T-cell response. During the innate immune response, the G-CX3CR1 interaction influences lymphocyte chemotaxis, and modulates the suppressors of cytokine signaling expression to dampen the production of type I IFN and interferon-stimulated gene (ISG)-15 expression by innate immune cells and the type I cytokine responses of memory T cells [55, 56]. Infections with one hRSV strain lacking the CX3C motif or treated with anti-G monoclonal antibodies to block binding of the CX3C motif to CX3CR1 resulted in increased levels of type I and III IFN . Additionally, through its interaction with CX3CR1, the hRSV G protein induces IL-10 in neonatal regulatory B cells, which downregulates Th1 cell responses. Furthermore, the G protein impedes inflammatory cytokine release by interacting with CX3CR1 and impairs the immune response to hRSV . However, stimulation of naive spleen cells by hRSV or by the G protein induce substantial increases in IL-4 and CX3CL1, suggesting that the expression of G protein during hRSV infection may directly influence the cytokine or chemokine profile. Recent studies have shown that the G-protein can modulate the innate immune system by suppressing TLR4 signaling to baseline levels. Downstream of TLR signaling is a suppressor of the cytokine signaling family of proteins that negatively regulates the type of cytokine and chemokine expression that is inducible via TLR activation. The hRSV G protein also contributes to immune evasion by modifying host cytokine and chemokine responses whose expression is negatively regulated by suppressor of cytokine signaling (SOCS) proteins . The G protein can also interfere with the roles played by the host’s chemokines by reducing their homology to prevent the influx of natural killer cells and CD4+ and CD8+ T cells, suggesting that G protein expression during hRSV infection may have the adjunct property of reducing the antiviral response to promote hRSV infection or replication .
The membrane-bound version of hRSV G is possibly a target of neutralizing antibodies that bind to epitopes in its central conserved domain. Antibodies induced by the G protein are mainly involved in inhibiting viral replication and in immune modulation by interfering with the antibody-mediated neutralization response . It has been suggested that the G-specific antibodies that block G binding to airway epithelial cells or antigen-presenting cells reduce the disease severity, a finding supported by the fact that vaccine-induced anti-G antibodies can block G-induced disease and essentially have an anti-inflammatory effect that results in decreased disease severity. Recently, anti-G murine mAbs 2B11 and 3D3 have shown high efficacy in reducing viral lung titers and ameliorating virus-induced immune dysfunction by blocking G protein binding to CX3CR1 .
4.3 NS1 and NS2 proteins
NS1 and NS2 nonstructural proteins are the earliest and most abundantly expressed proteins upon infection with hRSV. They are postulated to perform various roles in hRSV pathogenesis, and they both participate in virus replication and suppress a major component of the host’s innate defenses [61, 62]. For example, hRSV infections provoke considerably weaker innate immune responses compared with other respiratory viruses. This characteristic is largely a consequence of strong interference from NS1 and NS2, which induce type I and III IFN signaling in human epithelial cells, macrophages, and dendritic cells by interrupting the Janus kinase-signal transducers and activators of the transcription 1 (JAK-STAT) pathway [63-65]. NS1 and NS2 impair the activation and effector functions of the interferon regulatory factory (IRF) of transcription factors that are critically involved in the induction of IFN, as well as in the proteasome-mediated degradation of signal transducer and activator of transcription 2 (STAT2) [66, 67]. It has been proposed that NS1 and NS2 impair the activation and effector functions of type I and III IFNs by targeting multiple proteins in the signaling cascade (e.g., RIG-I, MAVS, TRAF3, IKKε, TBK1, and IRFs) , as well as delaying the apoptosis of hRSV-infected cells, facilitating prolonged hRSV replication for increased viral yields, and mediating hRSV suppression of the anti-inflammatory activity of the glucocorticoid receptor glucocorticoid receptor transactivation . In the adaptive immune response, NS1 and NS2 inhibit dendritic cell maturation , possibly leading to reduced antigen presentation and T-lymphocyte activation, which in turn results in an incomplete immune response that contributes to hRSV reinfection. NS1 and NS2 were also found to induce abnormal signal transduction in bronchial epithelial cells through their enzymatic activities, with both of them negatively modulating the proliferation and activation of CD103+ CD8+ T cells and driving the abnormal differentiation of CD4+ T lymphocytes . These features can enhance disease severity and may be associated with asthma susceptibility after hRSV infection.
4.4 N protein
The nucleocapsid (N) protein polymerizes genomic and anti-genomic RNAs to form separate RNase-resistant nucleocapsids, thereby providing templates for the transcription and replication of the hRSV genome. The N protein is expressed on the surface of a variety of hRSV-infected cells, including DCs. In the hRSV immune response, the N protein, which acts as a major virulence factor, is the recognized major target for helper T cells and the memory cytotoxic T-lymphocyte (CTL) response in humans. By inhibiting T-cell activation, it impairs the acquired immune response and enhances hRSV reinfection susceptibility [71, 72]. Although the N protein does not induce neutralizing antibodies, the ring-nanostructures formed by the recombinant N protein make it a mucosal vaccine candidate because it affords some protection against hRSV to neonatal mice . In terms of vaccine development, N codon optimization may attenuate the viral virulence.
4.5 P protein
The phosphoprotein (P) forms part of the ribonucleoprotein complex by interacting with N and L proteins. It works as a multifunctional adaptor by regulating the connections among components of the nucleocapsid–polymerase complex, and is necessary and sufficient to direct RNA replication [74, 75]. During transcription and replication the P protein, a chaperone protein of N, helps to keep the newly synthesized N polypeptide in a soluble form. It is an essential cofactor for the large polymerase (L), in that it assists with translocation of the polymerase complex along the helical nucleocapsid. The P protein is thought to interact with a transcription antiterminator, the M2-1 protein. The unique P–M2-1 interface present in hRSV may provide a valuable antiviral target against this pathogen . P protein can subvert the extrinsic apoptosis process in a macrophage-like cell line persistently infected with hRSV, something that may be crucial for establishing persistent infections .
4.6 M protein
The matrix (M) protein, a non-glycosylated phosphorylated protein located in the inner surface of the viral envelope, acts as a bridge between the lipid bilayer envelope and the nucleocapsid and helps organize virion components at the plasma membrane before budding [78, 79]. M has been suggested to transport virions in virus-infected cells by interacting with the actin cytoskeleton . The M protein can also recruit and interact with new host factors, including proteins the involved in the innate immune response, cellular trafficking, and host transcription regulation, which is of great significance for antiviral strategies that target M to improve the efficacy of subunit vaccines .
4.7 SH protein
The small hydrophobic (SH) protein is a short transmembrane protein containing 64 or 65 amino acids. During infection it primarily localizes to the lipid-raft structures of the Golgi complex, and only very small amounts are associated with the viral envelope. Its function is less clear. Studies show that the SH protein is not involved in binding or infectivity; nor is it essential for viral replication in cell cultures, but it is involved in in vivo hRSV survival, at least to some degree . The SH protein is involved in the formation of pentameric ion channels and is not only a target for antibodies with Fc-mediated effector functions, but it can also activate the NLRP3 inflammasome leading to the expression of IL-1β . It was reported that the SH protein also inhibits apoptosis in host cells during infection by blocking the TNF-α mediated signaling pathway, which might be advantageous to in vivo viral replication . Antibodies to the SH protein can affect in vivo viral replication via ADCC . Finally, the live-attenuated hRSV vaccine containing the SH non-coding region has high immunogenicity in children.
4.8 M2 protein
The M2 gene is transcribed as two separate open reading frames (ORFs) that overlap slightly to encode two proteins, M2-1 and M2-2. M2-1, a multifunctional protein, acts as an antitermination factor for the transcriptional process to prevent the synthesis of shortened mRNA, which is a potential target for the development of virus replication inhibitors and contributes to RNA synthesis and mRNA stability by binding to viral RNA and the P protein . The small M2-2 protein is transcribed and translated by the ORF downstream of the M2 gene and is responsible for regulating RNA synthesis during virion assembly. Deletion of M2-2 can cause RNA replication delay, and its overexpression can prevent viral RNA synthesis. As the major targets of CTLs, M2 proteins induce robust T cell responses. A recent study showed that the recombinant hRSV G1F/M2 candidate vaccine, which includes the hRSV G protein domain and a CTL epitope in the M2 protein, can prevent vaccine-associated lung inflammation by regulating the level of CD4+/CD8+ central memory and Th1-type effector memory . Although the M2-2 deletion appears to restrict viral replication, it induces substantial neutralizing serum antibody responses , suggesting that the M2-2 mutant may prove important for the selection of candidate vaccines.
4.9 L protein
The L protein is the largest hRSV protein and, with its function as an RNA-dependent RNA polymerase, it is involved in viral RNA genome replication and mRNA transcription. The L protein is also associated with reduced efficiency of termination at gene-end motifs . Notably, the L protein can interact with the P protein, which is essential for its catalytic activity. There are few studies on the role of the L protein in hRSV immunity. Attenuating mutations in L may reduce virus activity, providing ideas for the development of hRSV attenuated vaccines.
hRSV commonly causes LRTIs with substantial morbidity and mortality in infants and the elderly. Advances in recent years have improved our understanding of both the innate and adaptive immune responses contributing to the control of hRSV infections. Protective immunity against hRSV re-infection is usually suboptimal, however, and recurrent infections are common throughout life. Better understanding of the characteristics of hRSV proteins, host immune responses against them, and the pathology caused by them, should identify new ways to develop more effective preventive and therapeutic tools or vaccines. This reviewed has placed emphasis on the F and G glycoproteins to provide helpful information for determining if, or how, these individual proteins contribute to protective immunity and vaccine antigen design, or could be targeted for antiviral drug development.
Conflict of interest
The authors declare no conflict of interest, financial or otherwise.
This work was supported by grants from Beijing Municipal Health Committee “The Special Fund for Capital Health Research and Development’’ (No. 2018-2-1131) and The Pediatric Medical Coordinated Development Center of the Beijing Hospitals Authority (No. XTZD20180505).
We thank Sandra Cheesman, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
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In reviewing the curriculum, Ysgol y Dderi resolved to adapt its planning to develop literacy and numeracy skills across the curriculum. Staff and pupils jointly contribute and are flexible to change. Visitors to the school have inspired and enriched learning opportunities. This case study represents the school’s curriculum development in relation to their progress in self-evaluation, planning and preparation, and realising change.
Ysgol YDderi is in the village of Llangybi near Lampeter, Ceredigion. It serves a wide rural area.
There are 135 pupils, including 21 who attend part-time. There are five classes, three of which are of mixed ages.
The school has identified a minority of pupils as having additional learning needs, including a very few who have a statement of additional learning needs. A few pupils are eligible for free school meals. English is the main home language of many of the pupils. There are a very few pupils from ethnic minority backgrounds in the school and none speak Welsh at home.
Stage 1: Evaluating the current curriculum within wider self-evaluation arrangements
Following two training days to consider the effectiveness of the curriculum, staff at the school judged that they were “uninspired” with the termly themes and that there was “no spark or excitement’ when they planned activities. The leadership team’s analysis of pupil achievement in language and mathematics showed that outcomes varied according to each cohort and judged that planning was not coherent enough to develop literacy and numeracy skills across the curriculum effectively. They also found it difficult to timetable all curriculum subjects and decided to adapt their planning to meet the school’s specific needs. Staff judged that the pupils did not have the necessary tools to gain full access to every aspect of the curriculum because their literacy and numeracy skills were not strong enough. As a result, they explored the possibility of planning activities that developed literacy and numeracy skills across the curriculum rather than teaching the curriculum subjects in individual, stand alone and unrelated lessons.
Staff have ownership over the school’s evaluation of the curriculum. They drive the agenda for change and ensure that governors, pupils and parents are included in all decisions and kept informed of the changes. The headteacher works in partnership with all key stakeholders to develop a successful and innovative curriculum. The school’s processes enable staff to concentrate fully on what needed to change over the mid-term and in the long-term. The school also had the confidence to be open to change in the short-term. If there is a need and an opportunity to improve provision, even if the school was not planning for this outcome, staff are in a strong position to respond very quickly and they are very flexible to the notion of change. The school plays to its strengths and uses the headteacher’s teaching commitment purposefully to provide ongoing evaluation of provision so that important messages are shared effectively with all members of staff.
While evaluating their current curriculum, the school considered the relevance of what was being presented to the pupils in relation to their day-to-day lives. Monitoring outcomes show that this did not happen every day and that pupils found themes such as ‘our neighbourhood’ and ‘me, myself and I’ both dull and uninspiring.
Stage 2: Planning and preparing for change
Leaders encouraged teachers to change their plans according to pupils’ outcomes, aspirations and interests. As a result, standards in language and mathematics across the whole school showed good progress.
The stimulus to plan in order to revise the curriculum is two-fold:
- the teachers had grown tired of the same old themes
- there were adequate standards across the curriculum
When planning activities, an initial emphasis was placed on providing creative ‘experiences’ for pupils. This is now developing further to include worthwhile opportunities to develop the four purposes outlined in Successful Futures, (Donaldson, 2015). Every visit, activity and visitor is planned in order to develop at least one of the purposes. If the activity does not contribute to the development of these core purposes, then the activity simply does not proceed. This follows a discussion with the staff and pupils at the beginning of each theme. The senior management team work very closely with individual members of the governing body in order to ensure that they understand the principles of the four purposes and the need to develop effective pedagogy. The senior management team believe that their involvement prepares them well to evaluate and develop a broad curriculum in relation to the areas of learning and experiences, especially expressive arts.
An initial focus was placed on the pace of lessons, ensuring that the teaching moved forward using the different themes. Leaders encouraged teachers not to concentrate on one theme for too long by changing the theme every half term at least and to include sub-themes as part of the main theme for up to a week at a time.
Leaders encouraged teachers and pupils to take risks and the headteacher gave freedom for this to happen in the classroom in order to develop the thinking skills of teachers and pupils.
Every stakeholder scrutinises books together before providing constructive written feedback that informs future planning well. The parents receive comprehensive information about the work that will be done during each half term. This enables them to take an active role in curriculum development. The school makes very good use of parental expertise. For example, a ship’s captain, the director of IBM, doctors and engineers, as well as clothes designers, have inspired many pupils following their visits to school.
Every new teacher is given the freedom to experiment with new learning styles during the first year. This is done by providing them with regular opportunities to observe their colleagues teaching in order to adopt a positive approach towards exciting teaching based on experiences. Following observations, every teacher writes a report that includes references to aspects of strength and areas that need to be developed. These are reviewed every term when the cycle of observations is repeated. The teachers plan lessons jointly, in order to develop the ability of new teachers to plan in accordance with the school’s vision.
Every member of staff looks for exciting learning opportunities independently and shares their ideas with others. When planning activities, teachers learn alongside the pupils – they share their frustrations at times as well as their excitement and enthusiasm. They take great pride in developing unique projects, for example creating marigold ointment using Meddygon Myddfai recipes, opening an international pop-up café for parents, recreating Ann Boleyn’s prosecution, and hosting a music festival named Glastondderi.
Stage 3: Realising change
A long-term overview of the subjects ensures that they meet the requirements of the curriculum. The school’s plans focus on more specific aspects of the curriculum and provide deeper learning opportunities. All pupils contribute to the planning at the start of every half term. This means that the pupils take ownership of their learning. Although there is a whole-class plan in place at the start of every half term, the pupils and staff are flexible to change, and current issues change the direction of the learning.
Every half term, each class plans an off-site visit and also invites a guest to visit them. This enriches the children’s learning experiences and improves their extended writing work when writing for a purpose and from experience. It brings the world of work into the classroom and opens doors for possible interesting careers. Staff are passionate and open to continuous learning, and take pride when a pupil leads the learning. By inviting local, national and international visitors to the school, the children become very aware of their Welsh identity.


February 16, 2007
Florida’s Central Gulf Coast: Lightning Capital of North America
By Darack, Ed
Barely above sea level, dotted with lakes and swamps, and surrounded by semi-tropical waters, the Florida Peninsula is so dominated by moisture that this land is probably best described not as terrestrial at all, but as terraqueous.Enveloped by warmth and humidity for much of the year, the peninsula's skies deliver wave after wave of rain, most famously from lumbering hurricanes, but far more frequently from swift, ephemeral thunderstorms. Sometimes solo, sometimes marching in groups across the landscape like armies, the towering storms form more often in the skies above the Florida Peninsula than in any other location on the continent. The highest concentration of thunderstorms occurs over the state's central Gulf Coast, the lightning capital of North America.
A map view of the Florida Peninsula grants quick insight into why so many thunderstorms sweep across Florida each year: the warm Gulf of Mexico lies to the peninsula's west, the Caribbean Sea to its south, and the Atlantic Ocean to its east. A more detailed analysis of the peninsula's climate reveals the influence of the tepid Gulf Stream current, which originates in the Gulf of Mexico, runs southward along the peninsula's west coast, and then wraps around the Florida Keys before shooting north along the state's east coast.
The peninsula is practically immersed in warm, moist air- thunderstorm fuel. Furthermore, while rolling hills define a few parts of the Florida Peninsula, this region is largely devoid of topographic relief. The highest point in the peninsula is the 312- foot Sugarloaf Mountain, northeast of Tampa Bay (Britton Hill in Florida's Panhandle is slightly higher at 345 feet above mean sea level, making it the highest point in the state). This flatness allows thunderstorm cells to go freely wherever winds drive them. Wind is the essential factor in why the central Gulf Coast is the thunderstorm-and lightning-capital of North America.
During the height of thunderstorm season, sea breezes drive moisture-laden air from both coasts inland, and seasonal pressure ridges corral these moving air masses into a corridor that runs through the middle of the peninsula. But the Atlantic sea breeze is typically more powerful than that of the Gulf, so the air masses don't meet in the middle of the state. Instead, they collide in the central Gulf Coast region. The amount of incoming solar radiation, called insolation, reaches its zenith in June and July, convectively lifting these air masses during sweltering summer afternoons and evaporating water from the moist landscape below.
As early evening arrives, lightning can be seen flashing as rapidly as 30 times per second in any of these storms. These dramatic cumulonimbus, called by some the "mountains of Florida," eventually succumb to a nighttime death. Just a few hours later, however, the lightning life cycle of the central Gulf Coast will begin anew at dawn.
Lightning strikes the turquoise waters, white sand beaches, and lake-studded flatlands of Florida's central west coast more frequently than in any other region in North America. The city of Tampa, which derives its name from a local Native American word likely describing furious lightning strikes, lies in the heart of this thunderstorm corridor.
Two primary seasons (the cool and the warm) interposed by two transitional seasons (spring and fall) define the Florida Peninsula's annual climate. While thunderstorms can and do strike the state during the cool months of November through February, the skies of Florida-specifically those of the central Gulf Coast region- are most prolific in generating lightning-wielding cumulonimbus cells during the warm season. Once the relatively tranquil winter months have passed, the skies above the state's central Gulf Coast become convectively restive from March through May. In the warm season of June through September, thunderheads roar across the region almost daily.The majority of the average 100+thunderstorm days per year in the Tampa Bay region fall in June and July. And with this North American record number of days with thunderstorm activity comes an average lightning-strike density of 14.5 strikes per square kilometer annually, the highest on the entire continent.
Long before Europeans arrived and decimated the local native population, the Colusa Indians thrived in what would later become known as central Florida. One of the major hubs for the Colusa was a town they called "Tanpa.""Tanpa" ultimately became "Tampa," as the latter is easier for those of European descent to pronounce. However, historians continue to debate the actual meaning of "Tanpa." Some claim the word translates to "place to gather sticks," referring to driftwood found in the area and used for firewood. Other historians contend that "Tanpa" translates to "sticks of fire," indicating "sticks" of lightning.
The two translations aren't necessarily contradictory. Their connection becomes apparent during Florida's rare droughts: lightning storms during the drier, cool season have spawned wildfires that have incinerated tens of thousands of the peninsula's acres.
While Florida's central Gulf Coast can claim more thunderstorms and lightning strikes per year than any other place in North America, it pales in comparison to the global king of cumulonimbus activity; the mountains of Rwanda in Equatorial Africa boast over 200 thunderstorm days annually (Rwanda lies on the equator, so it has two warm, rainy seasons).
ED DARACK is a freelance writer/photographer; visit his website at www.darack.com.


Hans Martin Hanslin, Trond Maehlum, Arne Saebo
DOI: https://doi.org/10.1016/j.ecoleng.2017.06.019 | Published online: 14 July 2017
Area-efficient constructed systems for stormwater management and bioretention may involve large fluctuations in subsurface water levels. Such fluctuations challenge vegetation by forcing roots to explore deeper layers to access water during dry periods. In a controlled experiment, we studied growth patterns and the ability of Phragmites australis roots to track subsurface water level fluctuations of differing amplitude and frequency in substrates with contrasting water-holding capacity. We found that P. australis was able to adjust its rooting pattern to considerable subsurface water level fluctuations (to well below 120 cm), but that substrate characteristics can restrict its ability to adjust to larger fluctuations. Fluctuation amplitude was the driving factor for plant growth and biomass allocation responses, while substrate characteristics and fluctuation frequency were less important. When not exposed to large water level fluctuations, P. australis grew larger shoots and only explored intermediate rooting depths. There was a negative relationship between root and rhizome biomass, showing a resource-based trade-off and short-term costs of adjusting rooting patterns to large water level fluctuations. These results indicate that P. australis is suited for systems with considerable subsurface water fluctuations, but constraints on its flexibility need to be investigated.


I often get emails from well-meaning people who want to do the best thing for their families when it comes to buying nutritious food—but as is the case for so many of us, the best choice is often cost-prohibitive. When it comes to fruits and veggies, we know that eating fresh, organic fare is the optimal choice. Since buying organic can more than double your food bill, it helps to know if there are items for which buying conventionally grown (not organic) is safe, from the standpoint of not being laden with a high number of pesticide residues.
According to the Environmental Working Group, their Shopper’s Guide to Pesticides in Produce ranks pesticide contamination on 48 popular fruits and vegetables. EWG’s analysis is based on the results of more than 35,200 samples tested by the U.S. Department of Agriculture, and the Food and Drug Administration. It’s important to know that these pesticide residues remain on produce even after items are washed and, in some cases, peeled. Recent studies of insecticides used on some fruits and vegetables found that children exposed to high levels were at a greater risk of impaired intelligence and ADHD.
Each year, the Environmental Working Group releases a list of fruits and vegetables called, “The Dirty Dozen.” The Dirty Dozen lists the fruits and veggies that have been contaminated by multiple pesticides and have higher concentrations of pesticides. This year, strawberries ranked at the top of the list for detectable pesticide residues.
We all set goals and we all want the best for our lives. Many of us fall prey to self-sabotage and become our own worst enemies. Why? What are the barriers that hold us back, and how can we break free? These barriers lie between your life right now and the life you want.
If you lack self-worth, at some point in your life someone taught you that you are not worthy. As a child, we believe that which we are told by others. Many of us were given messages that we are not worthy and have less value than others. We internalize the idea and buy into the lie. The good news is that anything that can be learned also can be unlearned.
You were put on this earth to be great and to make a contribution to the world. No one is here just taking up space. Bishop T.D. Jakes says that we have to step out of our HISTORY and into our DESTINY. You have a gift, and your duty is to identify your gift and do something good in the world with it.
Barrier #2: Feeling Unworthy
If the subconscious self-limiting belief that holds you back is lack of self-worth, only YOU can fix this. This is the tricky part. No one else can make you feel worthy or give you self-esteem, as both come from the self.
We all have goals and dreams for our lives. In order to live the life that you really want, you have to break through your self-imposed barriers. We each are where we are today because of what we believe about ourselves to be true and what we tell ourselves about ourselves and life. This is our STORY. We repeat it over and over and brain wash ourselves into believing that we can’t have better because of who we are or what has happened to us. The truth is that we can be whatever we decide to be, but in order to change our external environment, first we have to shift our internal environment. You were put on this earth to be great and to make a contribution to the world. No one is here just taking up space. You have a gift and your duty is to identify your gift and do something good in the world with it. The great Bishop T.D. Jakes says that we have to step out of our HISTORY and into our DESTINY.
We all set goals and we all want the best for our lives. Many of us fall prey to self-sabotage and become our own worst enemies. Why? What are the barriers that hold us back and how can we break through? What lies between your life now and the life you wish you had?
Dear Tara Marie,
I really need some inspiration. I’m having a tough time getting to the gym regularly and eating well. I don’t know what’s wrong with me but I am feeling really unmotivated, and I just hate what’s happening to my body after all of the hard work that I put in to get where I am now. I really need some inspiration. Can you help me?
Thanks, Carolyn, New York City
I have gone through what you are describing many times, especially after a knee surgery, serious injury or an illness that takes me out of my usual routine for an extended period.
Two things are happening: 1) you are physically out of shape and not where you want to be, and 2) you are mentally out of shape and not where you need to be to make a shift in your life.
There is a mind-set that you had when you were at your physical peak, and you need to get this back, as well as get your training on track.
We want to slowly get your body moving toward your goal and, at the same time, get you mentally in the game of consistent training and conscious eating.
Try my 3-week jump start plan to course-correct fast!
Last week I posted a blog that focused on two of the many ways to increase strength training intensity: increasing the total load and decreasing the amount of time between sets. If you missed that newsletter, check out my blog post, “Two Simple Ways to Increase Strength Training Intensity.”
This week I want to highlight two other ways to ratchet up the efficacy of your strength training.There’s a very specific recipe to build muscle: work the muscle; feed the muscle; rest the muscle. Within this recipe are many variables, and depending on how they are manipulated, you will either mitigate or enhance your results.
I’m often asked how to increase the intensity of a strength training workout to maximize results. It’s important to understand that intensity is relative, as what may be hard for you will be easy for someone else. Often when I advise clients to do high-intensity strength training, they remind me that they’re not very strong. Regardless of your current level of strength, you can make your training high-intensity relative to your abilities. If you’re going to make time for a workout, make the time work for you—meaning, if you’re disciplined enough to exercise, do so in such a way that will maximize your results.
With respect to strength training, the important thing to remember is to manipulate different variables that will force your body to work with greater loads. Strength gains occur when you require your muscles to adapt progressively to a higher level of resistance. This occurs when you increase the intensity. If you never increase the intensity of your training, your muscles adapt to the routine and you will eventually cease to progress.
Let’s look at two effective ways to increase the intensity of a strength training session. Remember, strength training can mean weight training with barbells and dumbbells, exercising with bands and tubing, or even cleverly using your own body weight. All of these forms of training can and will increase muscular strength, if done properly. Again, muscles gain strength when you require them to adapt—they will only adapt when you give them a challenge.
As someone who struggled greatly to mold myself into the person I wanted to become, I’ve had a life-long fascination with high-achievers and people who seem to effortlessly succeed. My fascination led me to study people I admire in an attempt to raise the bar in my own life. I do believe that we’re here to constantly learn, improve, and teach what we know to others. In this sense, we’re never done—we can never stop learning or striving to improve, as the point of being here is to do something with our lives that contributes to the world in a positive way.
As part of my study of people who achieve and attain the highest level success, I also had to focus my attention on those who don’t. In this category of people, I identified two distinct groups: those who try and fail and eventually give up, and those who never try in the first place. People in the latter group confound me, yet fascinate me, the most. What would make anyone choose to sit on the sidelines of life while the rest of us are out on the field playing the game?
I’ve had conversations with private clients recently that made me want to address this in greater detail.
As a food addict myself, I understand the knee-jerk reaction to reach for food when what you really need is to feed your soul. It’s when you use food to feed yourself in any way other than to satisfy a nutritional requirement that you go from “eating” food to “using” food. “Using” food can quickly become “abusing” food.
I had a conversation with a client that prompted me to focus this blog post on the importance of indulgence as you learn to control compulsive urges around food, and teach yourself to eat for nutrition rather than comfort.
One thing I know for sure is that we all want and need to indulge. After a long day of work or taking care of the needs of others, we feel like we deserve it. When stress levels are heightened or we face mounting problems, the desire to indulge is magnified.
Since what is happening in our external world is out of our control and stress and anxiety are going to be a part of our lives forever, my advice to my clients is the same advice I follow myself—indulge more to lose fat.
A big shift in my life occurred when I decided that I deserve to indulge, and rather than do so with self-destructive behaviors like binge-eating, I instead learned to indulge in ways that are good for my physical and mental health.
As someone who used to be an emotional eater, I’m always sensitive to my clients who struggle endlessly with this issue. It’s such a complicated matter that I could (and likely one day will) write an entire book about it. For this week, I wanted to at least make it the subject of my blog post, as it seems to be a recurring theme in my work with clients.
I recently hosted a guest on my radio show, TARA MARIE LIVE, named Jesse, age 64. He is suffering terribly and feels trapped in an endless cycle of binge eating and the self-loathing that goes with it. Consumed with despair, he feels like he’s fallen into a dark hole and can’t see the light.
For people who don’t struggle with this problem, it is impossible to explain how FOOD can CONTROL every thought, action, and desire in an otherwise normally-functioning person.
For people who do struggle, it is impossible to put into words how out-of-control they can feel around a gallon of ice cream, a package of cookies, or any other trigger food. I had a client once tell me that she would literally salivate if she walked by a vending machine.
I’m currently working with a private client whose whole life is about food—what he ate for breakfast, lunch, snacks, and dinner; what he wanted to eat; what he should have eaten; what he will eat later, and what he misses eating (when he’s trying to be “good.”)
I remember those days well, but not fondly—when there was hardly room for fun in my life because all of my time was consumed with obsessing over food or being disgusted with myself for losing control around food. It was a horrible way to live and a terrible waste of time.
I always give my clients the same advice—it’s based on knowledge that I learned the hard way, as for years of my life I tried to solve my “food” problems by focusing on food.


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