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Kristian Hoffman and Lance Loud were best pals at Santa Barbara High School, bonding over a shared love of the Stooges, Velvets, Kinks and Sparks. They played music together in the Louds’ garage. And then the PBS docu-series An American Family was aired in 1973, changing everything. Kristian and Lance moved to New York, started Mumps, built up a following but never released an album…until now, nearly 50 years later, with a career-spanning retrospective. Though Lance Loud died in 2001, Kristian Hoffman carries on. Michael Shelley spoke with him for PKM.
Kristian Hoffman met Lance Loud in art class at Santa Barbara High School. The two formed an instant, lasting and complicated bond. Their musical collaboration started in the Louds’ garage with an ever-changing cast that included most of the Loud siblings and various musicians from high school and the neighborhood. When the Loud family was chosen to be the subjects of the PBS docu-series An American Family, often referred to as the first reality television show, it catapulted the naturally charismatic Lance into the national spotlight. Songwriter/keyboardist Kristian and frontman Lance ended up moving to New York City, forming Mumps, becoming regulars in the early CBGB/Max’s Kansas City scene, touring, releasing two singles, building a loyal following and eventually, after seven years of flirting with breaking through, breaking up.
The Mumps’ new release Rock & Roll This, Rock & Roll That: Best Case Scenario, You’ve Got Mumps has been called their “Great lost album.” It is a career-spanning retrospective that includes the band’s released output (two singes) along with previously unissued demos and early recordings. The release has been getting a fair share of press, some focusing on the band’s music, and some taking this time to re-visit the frenzy surrounding the original release of An American Family and the coverage of Lance Loud, and how his, and the band’s sexuality was perceived. Because we’re inundated with reality television, and because attitudes toward sexuality have changed so much since the show’s debut in 1973, and L.G.B.T.Q. characters are commonplace in mainstream entertainment, it’s hard to imagine how viewers reacted to An American Family, or how groundbreaking it was. Kristian Hoffman takes a look back at the music making, and the sexual politics.
PKM: When did you first meet Lance Loud?
Kristian Hoffman: I was in Santa Barbara High School, which was a very nice high school, very fancy. Santa Barbara is a real bastion of white privilege. It was kind of upper crusty, but it was lovely there, and he was in Mr. Baker’s art class, and that is where I met him. I saw him from across the room and he was making a paper-mache dodo bird. He was stapling avocado leaves on instead of feathers and I thought “My God, that guy is fucking weird.”
It turned out he was already the teacher’s pet, and the teacher was kind of a slightly closeted queen—you could say he was clever in the old-fashioned parlance of a euphemism for being gay—and Lance was already his favorite. They would sit at the desk and judge all the art of the other art students and say mean sarcastic things, and I thought “That’s a club I want in to,” and it was easy for me to sneak my way in there. We enjoyed each other’s company a lot and we sort of became best friends quickly. Later on, I learned the fact that, even though I was only 15 and a half, I had my own car… he liked that there was a sense of convenience that he could get around with a chauffeur.
PKM: The phrase upper-middle-class is often used when talking about the Loud family and Santa Barbara. Do you think that’s accurate?
Kristian Hoffman: No, it’s less upper. I come from incredible wealth and privilege, though my mother got disinherited because my grandfather supported Nixon and had a silver platter with Nixon’s profile on it. So I’m the one who came from the fancy background, but the Louds were kind of newly rich. They lived in a little Brady Bunch-type suburban home in a very nice neighborhood, but it was a typical late ‘50s-early ‘60s suburban development, so the whole idea of their incredible wealth… They succeeded because they were fun and interesting and charming and smart. Pat Loud [Lance’s mother] did come from a background of some privilege, but they were mostly just an up-and-coming couple in a moderate suburban area and they had big aspirations, but most of all they were really welcoming and funny.
PKM: So, at what point did it go from you and Lance being art class pals to “Let start a band”?
Kristian Hoffman: It was pretty quick. We connected over music. We had four favorite albums: Raw Power, The Velvet Underground & Nico, the first Sparks album and The Kinks’ Village Green Preservation Society. So that set us apart from absolutely everyone we knew. The Louds were very welcoming musically, so I remember we used to play Raw Power at swimming parties at their house all the time. So our tastes were kind of arcane and we really enjoyed that. And, of course, we soon learned to shoplift…I was the designated shoplifter because Lance didn’t want to go to jail, so we got new records every weekend and we used to listen to everything.
The Louds had a garage and here’s the cliché, they let all the kids play, because all the kids wanted to be in bands. Kevin was a fantastic bass player, Grant was a really good guitar player and songwriter and he was the good-looking one in the family so he had everything going for him. Both Lance and I were kind of goony and couldn’t do anything but it just turned out ultimately that we were the ones who stuck with it, but we were all allowed to play it in the garage and Pat said, “I’ll let everyone practice back there as loud as you like and as long as you like, but you have to let everyone in the band who wants to be in it.” So we ran through all kinds of high school students. Ultimately, we got Jay Dee Daugherty on drums, who we also went to high school with, and he later went on to fame with Patti Smith without us.
PKM: So everyone in town wanted to be in a band… or were you guys outcasts?
Kristian Hoffman: It was a social thing at the end of the Sixties. It was what you did with your spare time in California. You were either going to go be a surfer, which we made fun of, or you wanted to be in a band. Almost everyone we knew from high school wanted to be in a band.
Everyone would listen to KIST [107.7 FM] and check the Hit Parade in the back of the Santa Barbara newspaper. Everyone I knew was just into music. There was another guy who shoplifted records in Santa Barbara High School and I’d see him walking up and down the high school halls with the big shopping bag full of records, and he’d sell you a record for a dollar, so everyone was doing it. Music was kind of the Bitcoin of the time. You could decide whether or not you liked somebody. We loved The Beatles, but if you were too into them… or if you loved The Beatles but hated The Monkees, then we hated you, because those songs were good… so everybody was snooty and divisive and sarcastic, which is fun.
PKM: As a teenager at the time, was Lance out? Was that a thing to do at that time and place?
Kristian Hoffman: At that time, I was under-versed in sexuality. I just didn’t know anything about it. I even had girlfriends for a brief time, although I didn’t really know they were my girlfriends. Then I became best friends with Lance, and I didn’t have any schooling in homosexuality… so when we met we felt a kind of bon ami… which if you rephrase it as a gay word, it’s pretty gay. I didn’t really understand it, but I felt at home with him, and he sort of was an outcast in high school, but he wasn’t specifically outcast for being gay. Although I did hear that Tim Bottoms, who was also a friend of ours, who went on and had a splash at movie stardom in The Last Picture Show and then was never heard from again, although he was in the movie that Sparks was in “Rollercoaster,” but in any case… he used to call Lance a faggot, which at first I didn’t even know what it meant, and then when I knew what it meant it didn’t bother me because I just thought “He’s a fucking idiot, and who cares what he thinks.”
But over the course of the end of high school, Lance brought me into my own sexuality and schooled me about that stuff and even arranged for me to have my first sexual experience because I didn’t know how to go about it and was very clumsy and inept. He arranged for me to have sex with his then-boyfriend and then it turned out it really wasn’t for me to learn about having gay sex, he was actually testing his boyfriend, and when his boyfriend went ahead and had sex with me, I had to drive Lance home and he cried the entire time, and I thought, “Why are you mad? I thought you were setting this up for me so I’d understand this stuff.” He didn’t speak to me for a few weeks afterwards. It was high teen drama.
So it became known to each other that we were gay, but it didn’t really figure into my self-image. I never really fit into regular society. I wasn’t really interested in it.
PKM: Tell me about the filming of An American Family.
Kristian Hoffman: When it started happening it just seemed ridiculous. I didn’t think anything would ever happen to it. The producer, Craig Gilbert, came to Santa Barbara and he’d been brought there to meet another family, this is as I remember it as a 17 year old, but I was at the cocktail parties where they all discussed this kind of stuff, and he just happened to go to a cocktail party at Bill’s work [Bill Loud, Lance’s father], and he picked the Louds as the family he thought was going to be interesting enough to document. It all seemed very random.
Lance Loud in conversation with his mother, from An American Family:
PKM: I always wondered if there were some nefarious motives behind choosing the Louds. You know, did the filmmakers have a sense that this All-American family might actually have a lot of dysfunction, and was that their plan all along to show the underside all along?
Kristian Hoffman: I can’t speak for their mindset. but it was not a troubled marriage to the point of divorce when they started filmmaking. I know the family was looking forward to showing off all their good sides. They were all articulate and had these wonderful dinner parties and everyone just loved them, so their home life was admirable and full of interesting people and I think what happened over the course of the filming was once people became cognizant of the camera as a witness, things that might have happened over the course of a few years got sped up.
Pat, as a person who was being cheated on, now had a witness. So, I don’t think the producers, even if they were psychic, they couldn’t have smelled out how much action there would be. Lance wasn’t transparently gay. He didn’t have a lisp, he wasn’t effeminate, and he was actually very muscular and talked like a regular guy.
There’s a scene where Lance is putting on makeup with his sisters in the bathroom and that got captured on film. Lance was just trying to be outrageous like David Bowie. We were very much of a musical bent, whether we could play or not, and music was central to our lives, and we always tried to dress like Marc Bolan or David Bowie and they opened us up to our sexuality in a way that might have been harder for generations before or after. So having a camera there almost seemed natural, like “We’re crazy and interesting, and we’re smarter than the other kids in the room,” and now we got to play it to the camera and be ridiculous.
PKM: How old were you when An American Family came out and what was watching it a surreal experience?
Kristian Hoffman: Lance and I moved to New York when I was 17, I had graduated high school early, and we only stayed there for about eight months because we didn’t really realize you have to pay your rent on time and stuff like that, but we’d already met David Bowie’s drug dealer, so it was very exciting. So, we went back with our tails between our legs, we were humbled and back in Santa Barbara. I get mixed up on these times, that was 1970 or 71… so anyway we thought the series was unbelievably boring, so we didn’t even care to watch it religiously. It just seemed like the moments that were kind of crazy were fun to watch and then in between it just seemed like a lot of filler and we’d already lived that shit anyway. It didn’t seem that revolutionary or interesting to us, and the other thing is, Lance never comes out in the documentary. Everybody put that on him. There’s a scene where he’s walking around the park with Pat and she’s troubled by his sexuality and the world he chose to live in in New York, at the Chelsea Hotel with this strange guy… he always found a guy who would let him live with him… maybe there was sex involved… I was too stupid to figure that out at the time… and Pat came and was just overwhelmed, and that was entertaining to us, but the series itself wasn’t that interesting to us, and when the reviews came out and it turned out it was an opportunity not to review the documentary as a documentary but to review how sad and misguided and middle class and blinkered the family were, that was a total shock to us. As an art student I would think “Does it show a truth that we haven’t seen before?” and I think the truth it showed was that any prejudices against the middle class are okay.
PKM: I take it that you and Lance and the family and the community in Santa Barbara did not accurately predict the effects of the documentary.
Kristian Hoffman: We had no idea. We were just kind of doing it as a lark. As I said, the family, I think, was glad to have a witness. They did have the sense of providence. Like “We’re a great family,” which they were, “We’re an interesting family,” which they were. You know Bill was kind of an amazing, hilarious guy and a really good friend to me over the course of our lives, but he was more of an old-fashioned “cheat on the wife – I’m the breadwinner – what I say goes” kind of guy. But, when Lance came out, he was completely accepting of him.
PKM: So, you and Lance eventually moved back to New York. How long did it take until you had the first version of Mumps ready to play gigs?
Kristian Hoffman: It’s confusing to me… When we got there, Jay was still in the band and we played one or two gigs with him, but then when Jay quit to play with Patti Smith and we kept switching drummers, and we lost our bass player, so it took quite a while to assemble the final Mumps who played Max’s and CBGB all the time. It was around the same time everybody else started playing there, in 1976, but we couldn’t hold it together, we’d go for months at a time without a gig, but we were writing songs and being musicians that entire time.
PKM: Were you commercially ambitious? Did you think the thing you were doing was going to connect to the top 40?
Kristian Hoffman: No. Our model was kind of a cross of all the things we loved at first, the songwriting of The Village Green Preservation Society, which I think was the worst-selling record in Warner Brothers’ history. And we loved the Stooges and we were both completely obsessed with The New York Dolls. I used to go see them five times a week. So we love the raucous rock & roll, but also the crisp, clever wordplay. So our idea was we could get a big enough following to maybe make some albums, maybe be as big as Sparks or maybe get lucky and become a one-hit wonder. We believed we could tour and make albums. That’s as far as our aspirations went.
PKM: I’m interested in that time and that cultural change, from the early ‘70s hippie and glam time to the 1976 New York City scene…
Kristian Hoffman: Don’t get me wrong, we hated hippies. We were in that tweener moment where we thought hippies were stupid stoners, when we thought “They just lie around and don’t do anything” and the Grateful Dead is the worst band in history.
PKM: Did you feel that change coming in the air?
Kristian Hoffman: We always felt “other”. And we always felt that the music we loved was “other”. Even though The New York Dolls were transparently based on The Rolling Stones and David Johansen was transparently the “other” Mick Jagger. To us they were the anti-Stones. They were more radical and weirder and welcoming and their lyrics were in your face and divisive and crazy and clever, and so that’s what we liked and we never identified with mainstream music.
PKM: So, did a light go off at a certain point? Did you make any 90-degree turns in presenting your music when you got to New York?
Kristian Hoffman: No, that moment is made up by journalists. That didn’t happen at all. Maybe later it became more ROTC, and you had to have certain aspects if you wanted to appear Punk. We understood it was a label foisted upon us by journalists as an easy way to describe the scene, but we didn’t mind being called punks because we were anti. Punks were differentiated from the mainstream and we didn’t mind that.
The first band we played with was Television, who I loved, but they transparently loved The Grateful Dead. That’s not Punky. They had 18-minute guitar solos, which we would snore through. When they did those kind of orchestral inter-exchanges of beautiful fluid guitar playing it was really well done and it wasn’t just jamming. They were trying to make something really transcendent and poetic, but were we like them? No. But did they like us? Yes. When Blondie came along, a band like The Shangri-Las, that’s a great idea. When The Ramones came along, a band like The Shangri-Las, that’s a great idea. They’re both based on the same songs and the same chord structures.
The thing that we liked was how everyone was different, but we all supported each other. All those bands were excited about the differences between them.
PKM: With you being the musical force, the songwriter of the band, and being Lance’s best friend, there must have been some frustrating times. I’m sure that Lance’s celebrity opened doors for you but, did you sometimes wish you could just concentrate on music?
Kristian Hoffman: I loved being in a band with Lance, but Lance was at times very difficult. He was the only person who sometimes didn’t show up for rehearsals.
PKM: When the band broke up was there an event or what did it just kind of putter out?
Kristian Hoffman: The specific thing was… there was this thing in the Soho News… they were very supportive and they were trying to help us get signed and they did this thing where they had four guys from the scene, one of them was Walter Lure, one of them was Cheetah Chrome, one of them was me, and I can’t remember the fourth one… and they put us all on the cover and they interviewed us all and of course I just was learning to drink. I didn’t have a drink until I was 26. So I was maybe two years into my drinking career and I had no idea how to control it, so I was completely plastered by the time they were interviewing us and they asked what I liked in music and I just said whatever labels I could think of, and I said “I love Seymour Stein, I love that label Swan Song” and I just joked about all these label owners because I thought “One of these people is gonna sign me,” because I was drunk. So the next day I get a call from Seymour Stein and he says “Do you really love me?” And I didn’t know what to do. I said “You’ve given so many bands chances and support that never would have had another chance, you really helped invent the audience for this kind of music…” I actually came out of that line of tripe in the middle of a hangover. So then he said, “We want you to come up and we’ll make a demo with you.” So we had a meeting with the Mumps afterwards and everybody was really excited, but with reservations because we were all getting along really poorly at that time because of the lack of success. We were like brothers, and we got upset at each other like brothers, so we were a little bit at each other’s throats. So we made the decision that if we got signed we’d stay together and if we didn’t get signed we would break up. So we did the demo, which is on all of the reissues, and it’s middling, but I think the songs are good, they gave us a kind of a rote producer who was trying to force us into a smaller sound and to be less crazy, and he thought he was helping us when he made the songs sound more normal, and we had three hours to record it and while we were recording it, this was actually in the Sire building, Seymour Stein invited me up to his office and he talked to me about that article and about loving him and I was kind of put on the spot and I thought “What the fuck? Is he still carrying that around with him? Doesn’t he run this entire label and doesn’t he have 300 other bands to take care of?” But I knew I was negotiating some kind of crazy moment, and then he pulled out a drawer and said, “Last night I had coke with Dee Dee all night.” I had never taken any drugs, but I knew that this was kind of an offer of friendship and kind of what people in the music industry share, and if I sat around and maybe took some coke with him it might make the meeting go more smoothly… but then I went back to the recording session and Lance started yelling at me “You just lost us our record contract! Maybe if you’d offered to give him a blow job or something!” so then I started crying in the middle of the session. I didn’t know what to do, and I don’t know if anything had happened between us if it would have made any difference at all. And it never occurred to me that I was attractive to anyone. Since then, people have told me I was good-looking, but I always thought I was ugly. So we had that plan, if they passed on us we’d had enough sour-pussing around and we wouldn’t continue any more.
PKM: It must feel cathartic that the new re-release is reaching a new audience. How do you feel about that?
Kristian Hoffman: We feel really blessed.
PKM: A lot of the coverage of the new reissue has focused on the sexuality of the band. I’m guessing it is nice to get some credit for being “pioneering”, but that you are not 100% comfortable with the idea of being labeled a “gay band,” is that right?”
Kristian Hoffman: This is a complicated question that used to be very simple. I haven’t ever liked being compartmentalized into a diminished field of comparison. Once you typify an artist as a member of a subset, it feels like a vehicle for marginalization, or dismissal.
I never aspired to be, a “gay” musician. I was never a “gay” songwriter or artist. I never started a “gay” band. I was blessed to work with magnificent artists who were “gay”. I can name drop: Klaus Nomi, Rufus Wainwright, Joey Arias, Kid Congo, Prince Poppycock. But they were not defined by “gay” either. Importantly, I also worked with, toured with, wrote songs for, played piano with, arranged and produced for loads of “straight” people too. Is their name prefaced with the word “straight”? Is Dave Davies a “straight” artist?
I am a songwriter. I am an observational songwriter, and I write from experience like many songwriters I dearly revere. I am also a postulatory songwriter: I can imagine a story or an instance or happenstance with which I have not been personally involved, and I can write about it from feeling, life experience, research and extrapolation. I am NOT a “Gay” songwriter. That unasked for qualification seems to limit the expected scope of my songwriting abilities, my experience, and my imagination.
In the Bay Area Reporter (and I know I’m wildly privileged to have so much support in the “gay” press), it was suggested that the Mumps’ song “Muscleboys” was “camp”. That song (which I did not write!) does have an obvious gay subtext, but it was not “camp” – it was about cruel disinclusion for superficial differences, and an unfortunate ROTC-like mental regimentation about what was then acceptable or desirable in “gay” culture. That isn’t “camp”. That is angrily and disappointedly observational.
I am completely ready to fail in cringeworthy lack of skill or inspiration, and be found inexcusably wanting in talent or vision, or just possibly to excel as an artist, without the word “gay”. I’m ready to fail at the feet of the great masters whether that master is Leonard Cohen or Jobriath. John Lennon or Cole Porter. One thing I am not wanting for: aspiration.
But then the “gay word” IS complicated. I don’t claim to be unique except as all humans are unique. But my story is peculiar.
Not everyone was in An American Family, thought to be the first televised delivery system of an openly “gay” character. Not everyone drew the insert for the first New York Dolls album. Not everyone was in one of the very first “punk” bands to ever play CBGB.
Not everyone got Mumps fan mail with enclosed hand drawn pictures of Lance, and heartfelt gratitude that he (and even later “we” – Lance, me and Kevin Kiely) had given them the courage to come out to their parents, no matter what the result.
Not everyone lived with openly gay artist David McDermott. Or was close friends with openly gay Diego Cortez. Or was told he has “cute legs’ ‘ by Arto Lindsay. Or was good friends with “gays” Brian Grillo and Tomata DuPlenty. Not everyone was close friends with all three of the “gay” Zone brothers from the Fast. That part is confusing. Not everyone had a boyfriend who was the drummer for Teenage Jesus and the Jerks. Not everyone was boyfriends with fantastic “gay” playwrights Donald Kreiger and Justin Tanner, or fabulous “gay” chef (and Elvis impersonator) Kash Brouillet.
So, although I did not purposely comport myself in any of those experiences as if “gay” were at the forefront of my persona or art or commentary, I was indeed “gay”. I was out to all my friends, gay and straight, since I was about 16. We made fools of ourselves everywhere! I went to gay bars with gay friends (and some straight friends too!) I had gay sex. I was beaten and left for dead on a New York City sidewalk for being gay. I know it’s not an oppression competition.
In fact, that last incident seemed oddly unremarkable to me, because everyone I knew was always getting beaten up in that era for something, or nothing, by some violent stranger. I had an SF Hippie chase me down the street and actually stab me with a knife, “to the bare bone” as they say, while he was screaming in my face: “You fucking punks! Punks! Punks! Punks!” after playing a night at the Mabuhay with the Avengers.
But the continuing oppression of gays, either by typecasting as a de-legitimizing ploy, or being found too “amusing” to be taken seriously, or being thought of as “pretty good for a ‘gay’ songwriter”, or most recently being inexcusably oppressed by a U.S. Supreme Court ruling that institutionalizes that homophobia is now protected by law for “Catholic Charities”- it does make it wildly important to stand up and be counted for gay rights. It is a source of some troubling confusion for me. Can you spell Matthew Shepard? I wrote a song about him, upon which I duetted with that other “gay” artist, Rufus Wainwright. Is being appalled at that murder of an innocent young man who was found somehow unacceptable by prejudiced morons – is that “gay”?
“Sing, sing, if you’re glad to be gay!” I’m no Tom Robinson. I guess I’m an idealist. I’m not “proud” or “glad” to be gay. I don’t need to be “gay” to be “other”. I am proud to be “other”. I am proud to be renegade in my tastes and aspirations!
In retrospect, mostly because of “An American Family”, Lance and I were given an odd platform. Or had one thrust upon us. Maybe we were not adult enough to recognize it. Or smart enough to use it for public good. Or maybe that responsibility was too great for us.
Maybe we weren’t “activist” enough, although I do think by being resolutely openly gay and expecting to be treated as completely equal to our companions and idols, we were always default activists.
But does that mean that I can’t write a song that will resonate with a “straight” audience in equal measure as a “gay” audience? I don’t know. Is being “clever”, “melodic”, “satirical”, or “amusing” merely “gay”? I don’t know. Can I, as “gay”, not identify with every human feeling of want or deprivation or love or adoration or comfort or family?
All I know is this “gay” qualification or surname is put upon me. I don’t choose it. But I will stand up for my sexuality and the sexuality of others as, ultimately, completely unremarkable. What is remarkable in all artists and human beings is how they comport themselves in relation to their fellow humans, and the world. In what I dare to hope is an amusing fashion.


text:
Today’s report was written by a guest blogger, Alex Johnson, who also happens to be my husband.
26 August 2020
In the late afternoon last Saturday, the wind shifted and we got our first breaths of fresh air all week. We even saw actual clouds and blue sky for the first time in 5 days! Also fortunately, the thunderstorms predicted over the weekend bypassed us, and since then the weather has been much more cooperative for the firefighters: our marine layer came back (which at least helps in the lower elevations near the coast), the winds have been relatively calm, and the temperatures have been more moderate.
We no longer have ash and burnt vegetation falling continuously from the sky. Only sporadic ash fall now. However this morning the smoke came back, so our air quality is terrible again.
Finally, the fire crews were able to construct fire lines over the weekend to protect our area of town. Two lines were constructed. The primary line runs from Wilder Ranch at Highway 1 up to the far upper reaches of the UCSC campus (at Twin Gates) and then down to Highway 9 south of Felton. A secondary line runs through private land between the Moore Creek Preserve and Wilder Ranch up to Empire Grade Road just south of the west entrance to the UCSC campus.
Yesterday I took a hike to have a look at the secondary break. Here’s what I saw:
In the areas I took a look at, they used bulldozers to widen existing ranch roads (dirt), to about 50 feet in width. While digitizing the lines on the map, I noticed that the firefighters appeared to do this where ever possible. In other areas it was evident they had to cut through heavy timber/brush.
Needless to say, with these fire breaks in and the improved weather, we are feeling very much relieved and more secure. We still have our bags packed and are ready to leave, however.
Also because I’m a mapping geek I created my own web maps, pulling together data from various sources so I can keep track of what’s happening. It includes these photos, the fire breaks, evacuation areas, and other info I’ve found useful. The maps above came from those web maps, so here’s a link if you’d like to explore:
The situation remains fluid, but at least the weather is cooperating for now. The breaks that have been established are protecting both the city of Santa Cruz and the UC Santa Cruz campus. Smoke in the air remains a problem, and air quality has ranged from not-too-bad to don’t-breathe-if-you-have-to-go-outside. Still, at least we aren’t likely to have to evacuate any time soon.

domain: geography


Lecturers set for strike over cuts plans
The biggest outbreak of industrial action by college and university lecturers in London for over two years is threatened next month in a worsening row over funding cuts, union leaders warned today.
The University and College Union (UCU) said education in the capital could face "widespread disruption" on May 5, the day before the general election, because of planned protests over "massive" cuts which would lead to job losses.
Union members at 11 further education colleges have all backed strikes which will lead to action next month unless there is a breakthrough in the row.
Staff at the University of Westminster and University College London (UCL) voted earlier this week in favour of industrial action, following a walkout last month by staff at King's College in London.
The university staff are threatening to join the May 5 walkout in protest at cuts the union said were nearing £1 billion, on top of £340 million of savings further education has to make in the next academic year.
UCU general secretary Sally Hunt said: "All the tough talk about cuts has moved on and it is no longer figures on paper, but people's jobs and access to education that are disappearing.
"We believe in the power of education to make a real difference to people's lives and do not think we should be slashing funding at a time when more people than ever need access to education. UCU members are still on the side of education and they will be fighting to save jobs and defend education."
The UCU also warned that a second round of strikes could be held at the University of Sussex in Brighton on May 5 in a row over plans to cut jobs.
The union said it had "little option" but to move towards strike action as up to 107 staff were due to receive redundancy notices in the next few weeks.
Ms Hunt said: "Industrial action is always a last resort but the bottom line is that serious job losses will impact massively across the University of Sussex and result in a far worse experience for students.
"It is essential that management properly addresses the concerns of staff and students and that talks progress in good faith."
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In a residence-based tax system, residents are taxed on both their local and worldwide income. South Africa has such a tax system, and legislative updates in the form of the Taxation Laws Amendment Bill effectively brought residents living overseas back into the tax ambit, where previously they could claim exemption on foreign income where they met certain legislative requirements. Now, South African tax residents abroad will be expected to pay tax on their foreign employment income, where they earn more than R1.25 million per year. This means that if you’re a South African abroad, you need to seek clarity on your tax status, in order to correctly determine your tax liability to the South African Revenue Service. As a South African abroad for work, it’s important to be aware of how these tax law amendments impact your situation – where you meet the requirements for tax residency, you will be expected to pay expat tax back home.
In South Africa’s residence-based tax system, there are three possible classifications for individuals that determines their relationship with the South African Revenue Service (SARS):
- Tax resident: an individual that meets the physical presence/ordinarily resident requirements for tax residency, who is expected to pay income tax on foreign and locally-sourced earnings.
- Tax non-resident: an individual who does not meet the requirements for tax residency and who is expected to pay income tax only on income sourced in South Africa.
- Tax resident temporarily abroad: A South African resident currently living and working abroad, with no intention to permanently relocate.
What is the current tax position for South Africans working overseas?
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- 60 of which must be consecutive
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Do you have to pay tax in South Africa if you work abroad?
Long story short, the answer to this question is affirmative. Before 2021, South African tax residents working abroad could claim tax exemption on income, as long as they met the requirements of the 183-day rule of being physically outside SA. Now, South Africans earning foreign employment income must pay tax of up to 45% (according to their individual margins) if they meet the requirements for tax residency back in South Africa.
South African tax residency: determines how much and where you’ll pay tax
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What happens if you are not ordinarily resident in SA? It’s possible to still be counted as a South African tax resident in a particular tax year if you have been on South African soil for more than 91 days in that specific tax year, as well as in each of the five prior tax years, a total that adds up to more than 915 days in the five years. This is what is known as the “physical presence” test. That’s right. If you stand still for long enough in South Africa, you’ll get taxed.
How does the foreign income exemption work now?
Section 10 of the Income Tax Act specifies how income earned for employment services rendered outside of South Africa is eligible for exemption from income tax. The threshold for this exemption is R 1.25 million per annum from 1 March 2020, which must include the value of package benefits such as accommodation, travel allowances, security and so forth.
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- You earn a certain type of remuneration
- You spend at least 183 days (+/- 26 weeks/6 months) in a consecutive 12-month period outside of SA providing services for a foreign employer, and
- Of these 183 days, at least 60 of them must be consecutive, or unbroken.
The foreign income exemption does not apply automatically just because you earn foreign income. You will still be expected to file a tax return back in South Africa and it is at this point that you will declare this income and request that the exemption be applied in your favour. This will mean having to show that you qualify for this tax relief, which will then be deducted from your South African liability in the form of a tax credit.
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- Ghee or Butter
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- 4 Whole Garlic Cloves
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- Peel vegetables and place on a baking tray.
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Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols
Reproductive Biology and Endocrinology volume 10, Article number: 9 (2012)
Variability in the subfertile patient population excludes the possibility of a single approach to controlled ovarian stimulation (COS) covering all the requirements of a patient. Modern technology has led to the development of new drugs, treatment options and quantitative methods that can identify single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted based on genotype. Unfortunately, despite the predictive power of these measures, no single biomarker can stand alone as a guide to determine the best treatment option. In the future, hormonal, functional and genetic biomarkers will be used together to personalise COS.
Modern medical science has made great advances in the understanding and treatment of subfertility. This review is not an evidence-based meta-analysis, but rather provides our opinion on what we foresee as the future for controlled ovarian stimulation (COS) and how treatment protocols could be optimised to improve the outcome for individual patients. It is worth noting that some of the studies available in the literature and reported here have limited sample sizes and may not be adequately powered to show significance.
Novel technologies have created new ways to evaluate and treat patients and provide them with a prognosis for overcoming their subfertility. Basic and clinical research coupled with advances in technology have led to the development of a wide variety of new treatment options, particularly in the area of COS. Follicle-stimulating hormone (FSH [urinary or recombinant (u-FSH/r-FSH)]) levels can be used alone or associated with luteinising hormone (LH) activity, which in turn can be provided in the form of human menopausal gonadotrophin (hMG), recombinant human LH (r-hLH) or human chorionic gonadotrophin (hCG [urinary or recombinant (u-hCG/r-hCG)]). In addition, the optional use of steroid hormones such as progesterone, oestrogen, testosterone or dehydroepiandrosterone (DHEA), and even the possibility of growth hormone treatment, could be considered following further research. Taken together, all these options tend to increase the complexity of treatment decisions. The discussion around gonadotrophin-releasing hormone (GnRH) agonist versus antagonist protocols during COS is another example highlighting the expanding number of treatment options and the urgent need to develop a rationale for making the best choice of treatment for each single patient.
Currently, demographic and anthropomorphic data are the primary sources of information used to provide a prognosis and guide treatment. Along with basic medical and nutritional information, functional, hormonal and genetic biomarkers are tools that could provide more accurate diagnostic and prognostic information. Nonetheless, there is currently no consensus in the literature around the world as to how these newly available tools should be applied for a personalised treatment plan in order to improve the outcome of COS. Presently, general patient characteristics determine treatment, disregarding unique characteristics that might influence the needs of the individual patient, and thus, the chance of success. Empirical decision-making based on broad generalisations translates to similar patients receiving similar treatments. Thus, conventional factors like age and previous cycle data are used to make vital treatment decisions. Quantitative biomarkers are utilised mainly to predict prognosis and to inform patient counselling, but the strong potential of these indicators as tools to personalise COS is often underestimated .
The multidimensional variability of the subfertile patient population renders a single treatment approach unsuitable to dealing with a wide range of patient characteristics. This diversity in the fertility patient population, together with the ever-expanding number of treatment options (Table 1), creates both the need and the opportunity for personalised treatment, including an individualised approach to COS. The goal of 'personalised COS' can be achieved by taking advantage of the information provided by advancing science and new technologies. Using hormonal, functional and genetic biomarkers to develop a standard method of customising COS will make it possible to consistently match the correct treatment to the right patient. The improvements in treatment decision-making will lead to less burdensome protocols, less risk of adverse events, better outcomes and cost efficiency.
How can we predict ovarian response and personalise treatment?
Age versus biomarkers
Age is the most commonly used predictor of fertility; increasing age inevitably results in substantial germ cell loss by the age of 40 . Statistics for pregnancy, live birth and singleton live birth rate also decline rapidly from the mid-thirties on . However, even though age is clearly linked to declining fertility, it does not affect all women equally. On an individual basis, the chronological age of an individual may not be as valuable a predictor of fertility as their 'biological age', which is defined by the hormonal and functional profiles. Thus, biomarkers quantifying hormonal and functional profiles are more useful as prognostic factors than age alone when predicting response and choosing treatment strategy. Finally, genetic screening can provide specific information about a woman's reproductive system that would not be accurately predicted by age, hormonal or functional biomarkers. By considering hormonal (FSH and anti-Müllerian hormone [AMH]), functional (antral follicle count [AFC]), and genetic biomarkers in combination, a complete picture of an individual patient's overall reproductive status can be formulated to provide a basis of designing an optimal treatment plan.
Hormonal biomarkers: AMH
Inhibin-B, FSH and AMH are hormonal markers that can be used to predict ovarian response to COS and success with assisted reproductive technology (ART). Although FSH levels are more commonly used to evaluate a woman's probable response to COS, AMH (as a paracrine product of immature follicles) is a more direct measure of ovarian status compared with other endocrine reproductive hormones. AMH is primarily produced by the pre-antral and small antral follicles, and correlates with the number of primordial follicles at the gonadotrophin-independent stage of follicular development [4, 5].
A small study showing the potential use of AMH measurement in a routine in-vitro fertilisation (IVF) programme prospectively enrolled 316 patients and considered 132 oocyte retrievals in women undergoing a GnRH agonist long protocol. When the calculated optimal AMH cut-off of ≤1.26 ng/ml was used to predict responses to COS, it was found to have a 97% sensitivity for predicting poor responses (< 4 oocytes retrieved) and a 98% accuracy in predicting a normal COS response. These findings indicate that circulating AMH levels may be a good indicator of ovarian reserve, and are highly correlated with ovarian response to COS .
In the first study designed to evaluate the use of a hormonal biomarker to determine treatment strategy, Nelson and colleagues compared the safety, tolerability and success rates of different AMH-based COS strategies in two IVF centres. In this prospective cohort study, 538 women were stratified according to their AMH levels prior to COS (low: 1- < 5 pmol/l, medium: 5-15 pmol/l and high: > 15 pmol/l). In both centres, doses were similarly determined by each patient's AMH level; high, medium or low doses of FSH were given to women with low, medium and high AMH levels, respectively. However, in one centre, the choice between the GnRH agonist long protocol versus a milder GnRH antagonist protocol was also determined based on AMH levels. Specifically, most patients at the first centre (regardless of AMH level) were treated with a GnRH agonist long protocol, while in the second centre, those with high or low AMH levels were treated with a GnRH antagonist protocol.
In both centres, low AMH levels were associated with a reduced clinical pregnancy rate (CPR), but the cohort of low AMH patients receiving the antagonist protocol had a median duration of treatment of 10 days with a cancellation rate of 5% compared with a duration of 14 days and cancellation rate of 19% for the group treated with GnRH agonist long protocol. As expected, women from both centres with normal AMH levels had similar good outcomes with no poor response and no incidence of excessive stimulation. However, the group of patients with high AMH levels, similar to the group with low AMH levels, had better outcomes using the GnRH antagonist compared with the agonist protocol. No patients with high AMH who underwent the GnRH antagonist protocol were hospitalised due to ovarian hyperstimulation syndrome (OHSS) compared with 13.9% in the high AMH level group who received the GnRH agonist long protocol. In addition, use of the antagonist protocol did not result in any cases of 'total freeze' to avoid OHSS. Furthermore, the improvements in COS safety and tolerability observed with the GnRH antagonist protocol were accompanied by higher CPRs in both the low AMH (11.1% vs 18.7%) and high AMH (40.1% vs 63.6%) groups . The data from this study should be confirmed in large, randomised, controlled trials, but suggest that AMH may be used as a precise and reliable predictive tool to determine treatment strategies that can improve safety, tolerability and pregnancy outcomes (Figure 1).
Currently, a limiting factor in the use of AMH as a biomarker is the variability seen between commercial kits and variation in results reported from different laboratories . This variability may be one of the reasons for the lack of consensus on the cut off values of AMH when deciding whether or not to proceed with ART.
Functional biomarkers: AFC
The number of antral follicles detected by ovarian ultrasound has gained acceptance as an indicator of ovarian reserve, a COS response prognostic tool and predictor of IVF success [9, 10]. In a study including 149 treatment cycles, Chang and colleagues found that AFC declined with age and was negatively correlated to day 3 FSH and cancellation rate. In the same study, when patients were grouped by AFC (AFC < 4, 4-10 or > 10), the mean number of retrieved oocytes was 2.0, 6.3 and 14.0, and ongoing pregnancy rates were 0%, 13.2% and 26.3%, respectively .
Another study investigated 113 women undergoing their first ART cycle. In this group, AFC was found to be significantly associated with AMH levels and the number of retrieved oocytes, with the number of follicles between 5 and 6 mm having the highest correlation to both endpoints. AFC was also found to be predictive of poor responses to COS, with the number of follicles sized 2-4 mm, 2-5 mm, 2-8 mm and 2-10 mm being approximately equal in predicting response .
AFC is a relatively easy-to-perform technique that is widely accessible due to the availability of ultrasound equipment. Despite its general acceptance as a predictor of ovarian response, the routine use of AFC has been hampered by the lack of a standard methodology that would permit valid comparisons of data from different centres, and thus facilitate the consistent assessment of AFC. In order to address this issue, Broekmans and colleagues suggested recommendations for the standardisation of AFC assessment in routine clinical practice. Basic clinical and technical requirements for AFC evaluation were defined and a systematic method of measuring and counting antral follicles in clinical practice was proposed (Table 2) . Hopefully, as these guidelines are adopted around the world, the accumulation of standardised, universally relevant AFC data will make this quantitative, functional biomarker an even more useful prognostic tool.
Similarly to AMH, AFC was initially used as a simple prognostic factor and subsequently become a decision-making variable. Following the initial establishment of AFC as a reliable prognostic factor, its use in matching patients with COS protocols was hypothesised. A first attempt to address this was the Consolidated Standards of Reporting Trials (CONSORT) analysis, which aimed to determine whether specific factors could optimally predict a response to stimulation in ART and then develop a treatment algorithm to determine the optimal starting dose of r-FSH . Results from a subsequent CONSORT study demonstrate that AFC, combined with other patient characteristics, can be used to personalise treatment and maximise COS response and, at the same time, minimise patient risk and treatment burden . The CONSORT dosing algorithm was used to calculate the dose of r-FSH with 37.5 IU incremental increases based on basal FSH, body mass index (BMI), age and AFC. Patients were assigned to r-FSH doses of 75 IU (n = 48), 112.5 IU (n = 45), 150 IU (n = 34), 187.5 IU (n = 24) and 225 IU (n = 10). Oocytes retrieved per cycle were 8.5, 8.0, 10.0, 12.0 and 8.0, and CPRs per cycle of 31.3%, 31.1%, 35.3%, 50.0% and 20.0%, respectively, were observed . The favourable retrieval and pregnancy rates seen in this preliminary study demonstrate the successful use of multiple biomarkers, including AMH, to achieve effective individualised COS (Figure 2).
The influence of genetic research continues to shape the scientific and medical landscape. Pharmacogenetics is the science of predicting drug effects based on the genotype of an individual. In the future, the treatment of a patient could be based on her individual DNA. Presently, even though the biological response to any given drug may be influenced by hundreds of genes, progress is being made in the identification of specific genetic variances, called single nucleotide polymorphisms (SNPs) that can predict the safety and effectiveness of certain drugs in individual patients. In the field of reproductive health, hormonal and functional biomarkers are more established as tools to predict ovarian response, but in the future, genetic biomarkers may well be the best predictive tool to guide individualised treatment.
Genetic traits that influence fertility may not have visible clinical signs or abnormalities. If a patient's genetic profile also diminishes her response to fertility treatment, the failure to consider the genotype when designing the treatment consequently leads to a suboptimal treatment strategy. For example, a subset of young, normogonadotrophic IVF patients may produce an adequate number of retrieved oocytes and normal oestrogen levels, but not respond to COS as anticipated. These women require high doses of FSH (> 2,500 IU) over long treatment periods and, despite good prognostic indicators, have low implantation and pregnancy rates [16–19]. One possible reason for this hyporesponder 'normal' population is that they may have a genetic predisposition to a reduced sensitivity to FSH.
FSH and LH synergistically regulate normal ovarian function and oocyte development, and the disruption of either hormonal signal could have an impact on normal ovarian function and stimulation response. Thus, the genetic variability that affects the innate activity of these hormones could provide valuable predictive information and help guide COS treatment choices. Mutations in the genes coding for LH [20–24], the LH receptor [25–27] and the FSH receptor [28–32] have been identified as possible causes of subfertility, as well as factors that may influence fertility treatment.
A common variant of the β subunit of the LH molecule (v-LH) is identified by an additional sulphonated sugar at asparagine (Asn)-13 . The v-LH polymorphism is found in populations worldwide, but has so far been most commonly identified in northern European countries . There is clear clinical evidence that the v-LH polymorphism affects FSH sensitivity and the ovarian response to COS. For example, in a group of 60 normogonadotrophic women aged 18-37 years with normal menstruation, basal FSH ≤10 IU/l and at least five oocytes retrieved, one homozygote and seven v-LH heterozygotes were identified. When these women were stratified by the cumulative dose of FSH used (> 3,500 IU, 2,000-3,500 IU or < 2,000 IU), one heterozygote fell in the middle range with the rest having had doses greater than 3,500 IU . In another study of 204 normogonadotrophic women, 21 v-LH heterozygotes and three v-LH homozygotes were identified. The FSH dose needed was positively correlated with the presence of the mutation, with a gradient in which the v-LH homozygotes and heterozygotes received a substantially higher cumulative dose when compared with the wild-type carriers (Figure 3) . These preliminary analyses suggest that the v-LH genotype may help identify a subgroup of potential COS hyporesponders who are less sensitive to FSH, and who would benefit from LH supplementation rather than stimulation with higher doses of FSH.
Hyposensitivity to FSH may also be caused by a genetic variant of the FSH receptor. Two FSH receptor variants that have SNPs in the coding region have been identified and well characterised . The SNP known as the Serine680 (Ser680) variant causes the replacement of Asn with Ser at the 680 position, which is located in the intracellular domain of the FSH receptor protein . Consistent with reduced sensitivity to endogenous FSH, carriers of this trait have higher FSH levels throughout most of the menstrual cycle, and a significant increase in both total menstrual cycle length and number of antral follicles . When this SNP was studied in a group of 161 women below the age of 40 years undergoing ART, the distribution was 45% for the wild-type (Asn/Asn), 29% for the heterozygote (Asn/Ser680) and 26% for the homozygote (Ser680/Ser680). Although peak oestradiol levels, numbers of pre-ovulatory follicles and numbers of retrieved oocytes were similar in the three groups, basal FSH levels were significantly higher for carriers of the Ser680 variant (6.4 IU/l, 7.9 IU/I and 8.3 IU/l for the Asn/Asn, Asn/Ser680 and Ser680/Ser680 groups, respectively). Furthermore, both the heterozygotes and homozygotes required significantly more FSH during COS compared with the wild-type group (Figure 4) . The second receptor variant, known as the Alanine307 (Ala307) variant, is generated through substitution of threonine (Thr) with Ala at the 307 position, located in the extracellular domain of the FSH receptor . There is a very strong linkage disequilibrium between the two SNPs. This means that women who possess Thr307 nearly always have Asn680 present on the same allele, and women who have Ala307 have Ser680 on the same allele . The link between FSH receptor SNPs and polycystic ovarian stimulation (PCOS) has been studied extensively; however, there is some variation in the results seen. Some studies have demonstrated higher levels of patients with Ser680 in the PCOS population , whereas other investigators have shown differences in basal levels of FSH depending on the presence of the SNP . Interestingly, it has recently been demonstrated that PCOS patients with the Ser680 mutation have a natural resistance to clomiphene citrate . This may prove to be very important in the field of ovarian stimulation in the future with clinicians devising their COS protocols according to factors including FSH receptor genotype. Additionally, the effect of the Ser680 SNP has been studied in the general population receiving subfertility treatment and results have been reviewed previously . Studies have reported conflicting results with some demonstrating worse outcomes with the mutation and others demonstrating positive outcomes. For example one study demonstrated higher pregnancy rates in the patients with Asn680  and another showed higher pregnancy rates in patients with Ser680 .
An additional study looked at FSH-induced oestradiol levels in women who were homozygous for the Ser680 variant compared with women with the wild-type (Asn/Asn). This represented the first attempt to develop a pharmacogenomical approach to COS. Ser680/Ser680 carriers were randomly allocated to two subgroups to receive a daily FSH dose of 150 IU or 225 IU, respectively. Age and BMI-matched Asn/Asn carriers, receiving a daily dose of 150 IU, constituted a third (control) group. Even though the treatment details, number of oocytes retrieved and fertilisation rates were similar, the wild-type group had higher oestradiol production after treatment with 150 IU/day of FSH compared with the Ser680 group given the same dose; conversely, when Ser680/Ser680 carriers were treated with 225 IU/day, this difference disappeared . These findings are consistent with carriers of the Ser680/Ser680 variant experiencing lower biological activity of both endogenous and exogenous FSH due to lower sensitivity of the FSH receptor to FSH. However, it should be noted that two further studies did not confirm that adjustment of the starting dose of FSH improved the hormonal response [43, 44]. Despite this, the findings of FSH starting dose modification studies raise an intriguing question about the interpretation of isolated markers, including AFC. In fact, the current literature suggests that AFC is effective in predicting ovarian response and choosing the right FSH dose; nevertheless, a pharmacogenomical approach to COS strongly indicates that, in at least one out of four patients with normal AFC (which reflects the frequency of Ser680/Ser680), the optimal FSH dose should be higher. This provides further support that AFC and genetic approaches should be integrated into determination of COS treatment protocols.
In addition to the two SNPs described above, there are also many genotypic SNPs found in the introns and untranslated regions of the FSH receptor gene; however, it is not currently known what physiological effects these mutations confer . Further mutations have been identified in young women (< 35 years) undergoing COS in the form of receptor splice variants . FSH receptor messenger RNA was isolated from the cumulus cells of women who demonstrated high or low response to FSH when treated with a GnRH agonist long protocol. Abnormal splicing products were identified that affected the ligand-binding extracellular domain. One variant was associated with a low response to FSH, and another variant was associated with a high FSH response .
Each patient's individual characteristics must be considered in order to determine treatment that will provide her with an optimal response to COS, while keeping the adverse events and treatment burden as low as possible. Specifically, the hormonal, functional and genetic biomarkers described here can provide the critical information needed to personalise treatment to best serve the individual patient. AMH represents ovarian reserve and can help determine how much longer a woman will remain fertile and if ART is a viable option. AFC represents the number of follicles that are maturing in each cycle and provides a prediction of the response to COS. Finally, the individual patient's genetic profile defines the underlying physiology that determines the meaning and interpretation of hormonal and functional biomarkers like AMH and AFC, predicting the effectiveness of FSH when stimulating the ovaries (Table 3).
In addition to using the patient's individual characteristics to determine which treatment protocols should be selected, this patient-specific approach could potentially be used to determine how treatment protocols are administered. The short, ultrashort, micro-flare and stop GnRH agonist protocols are all adaptations of the standard protocol for COS, generated by adjusting the timing and dose of GnRH agonist administration [45, 46]. Preparation of the endometrium is also a crucial step in the success of IVF. Further analysis of hormonal, functional and genetic biomarkers and their relationships with patient response to variations in treatment protocols could be used in the future, and additional clinical data are required to support this hypothesis.
Individual patient characteristics can be predictive of ovarian response, and these factors must be used to optimise the individual treatment regimen. AMH and AFC are good predictors of ovarian response to COS, and may be valuable in deciding which protocol and dose to use for COS. Additionally, initial data indicate that the use of AMH to determine protocol selection may reduce the incidence of OHSS, although further studies are required to confirm this. The hyposensitivity to FSH in a subset of women undergoing the GnRH agonist protocol despite other normal indicators was described by De Placido and colleagues . It is possible that this condition may be caused by genetic polymorphisms of LH, the FSH receptor or the LH receptor. Thus, genetic testing of normogonadotrophic women showing reduced sensitivity to FSH (e.g., a high FSH dose in previous cycles) may assist in tailoring subsequent treatment. Patients could be given higher doses of FSH if they are found to carry the Ser680 variant, or have LH added to their treatment if they are found to carry the v-LH polymorphism. As technology progresses and more powerful analytical tools are developed, predicting ovarian response using a single biomarker will not be sufficient to make the most accurate prognosis or to formulate a personalised treatment plan. In the future, the combination of hormonal, functional and genetic testing will be needed to ensure that the right treatment protocol is provided to the right patient. Finally, the patient's response to treatment should be monitored closely to determine if further tailoring of the personalised treatment plan is required.
antral follicle count
assisted reproductive technology
body mass index
Consolidated Standards of Reporting Trials
controlled ovarian stimulation
clinical pregnancy rate
human chorionic gonadotrophin
human menopausal gonadotrophin
ovarian hyperstimulation syndrome
polycystic ovary syndrome
recombinant follicle-stimulating hormone
recombinant human chorionic gonadotrophin
recombinant human luteinising hormone
single nucleotide polymorphism
urinary follicle-stimulating hormone
urinary human chorionic gonadotrophin
variant luteinising hormone
Ezcurra D, Bosch E: Individualised controlled ovarian simulation (iCOS): maximising success rates for assisted reproductive technology patients. Reprod Biol Endocrinol. 2011, 21: 9:82
Baker JW, Morgan RL, Peckham MJ, Smithers DW: Preservation of ovarian function in patients requiring radiotherapy for para-aortic and pelvic Hodgkin's disease. Lancet. 1972, 1: 1307-1308.
Akande VA, Fleming CF, Hunt LP, Keay SD, Jenkins JM: Biological versus chronological ageing of oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment. Hum Reprod. 2002, 17: 2003-2008. 10.1093/humrep/17.8.2003.
La Marca A, Broekmans FJ, Volpe A, Fauser BC, Macklon NS: Anti-Mullerian hormone (AMH): what do we still need to know?. Hum Reprod. 2009, 24: 2264-2275. 10.1093/humrep/dep210.
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A: Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010, 16: 113-130. 10.1093/humupd/dmp036.
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The authors would like to thank Dr Agnese Fiorentino for her helpful discussion of the manuscript. Medical writing assistance was provided by Michael Bankson and Kirsty Ratcliffe of Gardiner-Caldwell Communications, Macclesfield, UK. Funding for medical writing support was provided by Merck-Serono.
CA and PH have no competing interests to declare. DE is an employee of Merck Serono S.A., Geneva.
CA, PH and DE all contributed their opinions and were involved in the reviewing of the literature and writing of the manuscript. All authors read and approved the final manuscript.
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Alviggi, C., Humaidan, P. & Ezcurra, D. Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols. Reprod Biol Endocrinol 10, 9 (2012). https://doi.org/10.1186/1477-7827-10-9

domain: biology


As part of its blitzkrieg against post-Newtown gun control legislation, the National Rifle Association is trying to kill the provision of the Senate bill that cracks down on gun trafficking by imposing harsher penalties for “straw purchases” — that’s when someone buys a gun for someone who is prohibited from owning one, or for someone who is intending to commit a crime with it.
There is broad bipartisan support in both chambers for the measure, which would make straw purchasing a federal crime punishable by up to 25 years in prison. The provision is a key part of the Senate’s gun control package, which may be voted on next week. A House bill making gun trafficking a federal crime has a similar provision.
But this week, the NRA is demanding that the Senate change its drafting language. The Hill reports:
If a person buys a gun and sells it to another person, who in turn sells it to yet another person, the bill’s language could be used to punish the initial buyer of the gun, the NRA says.
“It potentially holds people liable for the intention of parties far down the chain of possession,” NRA spokesman Andrew Arulanandam wrote in an email to The Hill.
The NRA also wants to change language allowing the government to confiscate a convicted straw purchaser’s guns and ammunition, according to a draft copy of the group’s proposed changes to the measure.
The NRA’s position has outraged those who support the legislation as written. Groups supporting stricter gun control laws, like Mayors Against Illegal Guns, believe cracking down on straw purchases — one of the most common ways criminals get guns — and background checks, another key component of the package, are essential parts of the new legislation.
“As long as straw purchasers are willing to buy on behalf of criminals, law enforcement needs effective tools to pursue these individuals by making this activity a federal criminal offense instead of a slap on the wrist,” said Rep. Pete King (R-N.Y.), one of five Republican co-sponsors of the House bill.
Rep. Carolyn Maloney (D-N.Y.), one of the original sponsors of the House bill, told The Hill, “Reports about the draft NRA proposal suggest that it would water down even current law, making it harder — not easier — for law enforcement officials to keep guns out of the hands of criminals by increasing the threshold for convicting straw purchasers.” (On Wednesday, Rep. Maloney vowed to continue the gun control fight despite death threats phoned in Tuesday to her Manhattan district office. Police are investigating.)
Meanwhile, in the wake of last summer’s shootings in Aurora, the Colorado state legislature has passed a series of bills requiring background checks for all gun purchases and limits on the size of ammunition magazines. President Obama visited there Wednesday to draw attention to the state’s new laws and put pressure on Congress to follow Colorado’s lead.
Christi Parsons of the Los Angeles Times reported that after speaking privately with families of some of the Aurora victims, “Obama held Colorado up as an example of a gun-loving state that still embraces ‘common sense’ curbs on firearm and ammunition purchases.”
The state’s new laws are a “model of what’s possible,” Obama said, praising the state’s many “proud hunters and sportsmen” who supported efforts to make it harder for ineligible buyers to get their hands on firearms.
“There doesn’t have to be a conflict between protecting our citizens and protecting our 2nd Amendment rights,” Obama said. “I’ve got stacks of letters in my office from proud gun owners, whether they’re for sport or protection or collection, who tell me how deeply they cherish their rights and don’t want them infringed upon – but they still want us to do something to stop the epidemic of gun violence.”
Opposed to the new Colorado legislation, pro-gun lobbyist Dudley Brown said he and his allies will be going after those who supported it and shared this chilling metaphor with NPR’s Scott Horsley: “I liken it to the proverbial hunting season… We tell gun owners, ‘There’s a time to hunt deer. And the next election is the time to hunt Democrats.’”


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To say that this has been one of the most rewarding projects I’ve ever worked on is a start. But it’s not everything, and I’m not sure I’ll be able to express everything this project has meant to me and everyone else who has worked on it. It would have been cool if we only incorporated the tons of talented players and filmed around the cool locations that we did. But being able to pay tribute to a musician who meant so much to so many of us elevated the project to a special place of significance. It is an honor to be able to dedicate this project to the music and memory of Dante Bucci.
For those interested in the production process (which is often what I talk about on this blog), let me begin by thanking everyone who worked on the film. We had an excellent crew, and excellent players who braved the cold (I still shiver when I think back to those shooting days). Because if the music isn’t good, it doesn’t matter how nice the gear is, or if the microphones were placed in the optimal spots. The music is king, and all of the players rose to the occasion.
The production process ran like a proverbial well oiled machine. The three person crew (myself, Todd on camera, Kyle assisting audio), piled into my car, pulled up to the location with talent waiting, setup audio and video, and ran takes. We gave everyone three takes of the song to do what they wanted to do, then we quickly tore down and drove to the next location, charging the laptop in the car during the commute.
That’s not to say we didn’t have our fair share of problems. People ran late, we had to switch schedules and locations a few times, and we were kicked out of two of our locations (although the second time it wasn’t until we already had recorded 1.5 takes, so we had enough material). I am generally a proponent of the “ask for forgiveness, not permission” style of filmmaking, and in this indie production, it largely benefitted us. Plus, the happy accidents outweighed any of the road blocks. There were multiple times during production where we all thought, “wow, we couldn’t have planned that.” Examples of this can be seen at the Academy of Fine Arts shot, where all three players (who were not originally supposed to be in the same shot) were all dressed complimentary not only to themselves but to the walls of the Academy as well. Also, the 30th St. Station scene featured two musicians who were playing with no acoustic sound – only direct line instruments. So we were able to quietly work without bringing attention to ourselves by making lots of noise.
From there, post-production was the most intensive part of it all. With all of those players doing multiple takes of the song, the audio mix alone was a bear. Going through and finding the best material was a challenge that yielded a great reward, because after I was able to pick and choose the parts I liked best, everything seemed to sit really nicely together. Again, top musicianship.
Once the audio mix was mastered, we could move onto video editing. It was great working with Jay on the edit. Since he’s also a drummer, this job proved to be ideal for a video editor with musical timing.
Thanks to everyone who came out to the premiere on December 1st. It was a great evening of sharing music and stories. And we raised a bunch of money for charity. I’m feeling thankful all around, and am pleased to share this project with the world.

domain: artistic


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Harwich: Man suspected of shoplifting alcohol and chocolate
- Credit: Archant
A CCTV image has been released of a man wanted in connection with the theft of alcohol and chocolate from a shop.
The shoplifting offence happened when a man entered the Co-op store on Fronk’s Road shortly after 7pm on Wednesday, May 1, and stole a bottle of wine and a large chocolate bar.
He is described as white, aged in his late 40s and has grey hair.
Anyone with information on the man’s identity is urged to contact investigating officers at Harwich police station on 101 or Crimestoppers anonymously on 0800 555111.