Why Does My Friend's House in Gurgaon Get More Sunshine on Winter Mornings?

A friend asked me why his house, located in Gurgaon, India, received more morning sunlight in winter, and more evening sunlight in summer. He looked up the angles of sunrise & sunset in summer & winter.

Here's the sunrise and sunset angles for Gurgaon that was posted.

Sunrise : 63* NE
Sunset : 297* NW

Winters :

Sunrise : 116* SE
Sunset : 244* SW

I will deal with the direction, then the angles. Notice that the sun is depicted as rising and setting in the North East and North West respectively in summer and in the South East and South West in Winter. It doesn't change direction. It is simply that in summer, the sun rides much higher in the sky than in winter. As India is in the Northern hemisphere, the position of the sun is higher, i.e. more Northerly, than in winter, when it sits more to the South. That is to say, it follows a much bigger arc, which intuitively makes sense, as the sunrise to sunset time, i.e. the total hours of sunlight, are much longer in summer. That explains the NE, NW in summer and SE, SW in winter.

Now the degrees. This confirms what I said earlier- the arc traversed in summer is much bigger- 297-63=234 degrees than in winter- 244-116= 128 degrees. The sun sits lower, i.e. more to the South in the Northern hemisphere, hence the arc is flatter and lower.

While this explains why the sun should hang around for longer in summer evenings, it certainly doesn't explain why you enjoy sunnier mornings in winter. I looked into this as well. The workings are fascinating and made lovely reading. I would be happy to share if there is any interest at all.

It is commonly believed that the winter solstice in the Northern hemisphere is the day with the most delayed sunrise and the earliest sunset. Indeed, the play of seasons and longer-shorter day length in summer-winter is a function of the earth's inclination relative to it's geometric axis. This angle of inclination ( or "declination" as it's called) is about 23.4 degrees, so that the North pole always faces the sun in summer, while the South pole faces the sun in winter. The inclined axis doesn't change direction. It always faces the Polaris, which is why it's as "Constant as the Northern Star".

However, the earth also revolves around the sun. This orbit is slightly elliptical, so that in December, the earth is closest to the Sun, called Perihelion, while in June, it is at it's furthest, called aphelion. Due to a law of planetary motion, called Kepler's second law, the earth moves faster in its orbit at perihelion, i.e. in December, than at aphelion, i.e. in June. From the vantage point of somebody sitting in the Sun, the earth will appear to be moving almost 7% faster in December therefore*. From the earth however, the Sun's movement through the sky will appear delayed. Thus, towards the end of the year, the Sun is "late". Both sunrise and sunset are later than would be predicted by the earth's declination alone. The reverse occurs in June, albeit less accentuated. That is to say, the sun is "early". Both sunrise and sunset occur earlier than would be expected from the earth's declination alone.

Thus, there are two solar phenomena determining the sunrise-sunset cycle. The first is due to the earth's declination, and can be called the "geometric effect". The second is due to the effect of the elliptical axis, and is called the "clock effect".

In practical terms, what this means is that in December, the delayed sunrise from the geometric effect is augmented by the clock effect, while the earlier sunset from the geometric effect is countered by the clock effect. Thus, say at 40 degrees North, sunset starts to occur later in the day as early as Dec 8, rather than Dec 21, while sunrise starts to occur earlier much later- around Jan 6. The effect is around 16 minutes each way.

The reverse occurs in June. As the sun is "early", sunrise occurs earlier than expected even before June 21, while the peak in late sunset is delayed until July.

It's worth saying here that the Clock effect is invariant, regardless of latitude, while the Geometric effect is more pronounced the further away from the equator you go. At the equator, because the Clock effect predominates, sunset starts occurring later and later as early as November, while it's February before sunrise starts occurring earlier. Timewise, the Clock effect is least pronounced around the equinoxes, and most pronounced around the solstices.

Practically, this means that closer to the equator (Gurgaon 28 degrees North), the Geometric effect is minimal, and the Clock effect occurs for most of the variation in sunrise and sunset. At the equator, this amounts to only around 30 minutes between summer and winter.

In more northerly latitudes ( say Nottingham 53 degrees North), the Geometric effect becomes more pronounced, accounting for the very short days in winter.

Now back to my friend's query. Why are the mornings sunnier in winter? The clock effect should not contribute more than 16 minutes to a change in the time of sunrise, but the problem with invoking it is that sunrise occurs later due to Clock effect in winter, chiming in with the Geometric effect. Hence that doesn't explain the winter morning Sun. The most likely explanation is therefore either less cloud cover in Winter or more likely a South East facing window, which captures most of the sunshine that's available. This latter explains why South facing gardens are prized in more northerly countries such as the UK.

* Kepler's second law - sometimes referred to as the law of equal areas - describes the speed at which any given planet will move while orbiting the sun. The speed at which any planet moves through space is constantly changing. A planet moves fastest when it is closest to the sun and slowest when it is furthest from the sun. Yet, if an imaginary line were drawn from the center of the planet to the center of the sun, that line would sweep out the same area in equal periods of time. For instance, if an imaginary line were drawn from the earth to the sun, then the area swept out by the line in every 31-day month would be the same. (http://www.physicsclassroom.com/class/circles/Lesson-4/Kepler-s-Three-Laws)

Why are West Coasts Warmer in the Northern Hemisphere?

The Coriolis effect diverts winds in the Northern hemisphere to the right, and in the Southern hemisphere to the left. Thus, in the northern hemisphere, winds blowing from north to south will be diverted westwards, while winds blowing from south to north would be diverted eastwards. The reverse will happen in the Southern hemisphere.

The Coriolis effect is more pronounced the further you go from the equator, i.e most pronounced at the poles, and negligible at the equator (which is why you almost never get cyclones at the equator itself. Cyclones rarely occur in the latitudes between 8 degrees north and 8 degrees south).

So far, so good, but this is all in the books, therefore not novel. I tried to think of a practical application of this that cannot be gleaned from the books. If one puts the two things above together, one can hypothesise that winds blowing southwards from the North pole would be directed westwards, and thus hit east facing coasts, while winds blowing northwards from the equator would be directed eastwards, and thus hit west facing coasts. It should follow therefore, that for large landmasses, equilatitudinal places should be warmer on the West coast than the East coast.

But are they?

So I randomly picked three pairs of locations, on East and west coasts, all reasonably to the north (so that the Coreolis effect would be prominent) to compare their average temperatures. By comparing places located at sea level, altitude is largely eliminated as a factor. Here are the results.

Arviat, located at 61 North on the Nunavut peninsula on the East Coast of Canada, has an average annual temp of -9 degree C. Hooper Bay, 61 North, located on the west coast of Alaska, USA, has an average annual temp of -1.7 degree C.

Portland, Maine, 43.66 North, on the Eastern seaboard, has an average annual temp of 7.4 degree C. Newport, Oregon, 44.63 North, on the West coast, has an average annual temp of 10.7 degree C. Note that Newport is actually a degree north of Portland.

To avoid local variations, I then took two places virtually miles apart, facing each other across the Bering Strait at around 65 North. Lorino, located on the East coast of Russia, has an average annual temp of -6 degree C. Teller, Alaska, on the West coast has an average annual temp of -4.9 degree C.

In the Southern hemisphere, things should reverse, and the East coast should be warmer. And it is. Two South American towns located at around 36.5 South-Concepcion, on the West coast of Chile, has an average annual temp of 12 degree C, while Santa Teresita, on the East coast of Argentina, averages 15.2 degree C.

Moving to Australia, we consider Sydney on the East coast, averaging 18.5 degree C annually, compared with Bunbury on the West coast, which averages 16.8 degree C. Both are around 33-34 degrees South.

Interesting, isn't it? Although the pairings were completely random, I deliberately left out places in the extreme south of South America, as it's very mountainous down one coast.

Permissive Haplotypes Are the Fertile Ground for Disease Causation

Fully 95% of subjects with essential polycythaemia and 50-60% of those with Essential thrombocythemia or Primary Myelofibrosis have a JAK2 V617F mutation. What is less well known is that this particular mutation arises preferentially in subjects with a certain haplotype- the so called 46/1 or GGCC haplotype, present in 50% of the general population. In the other 50%, myeloproliferative neoplasms (MPN) are distinctly uncommon.

In around 150 SNP haplotypes drawn from Caucasians in a British population, haplotype 46 and haplotype 1 were almost identical, except for a single base. These two haplotypes, together designated as 46/1 are found ("tagged") in 2 SNPs- rs 12343867 and rs 12340895. When the base present in either of these 2 SNPs is guanine rather than cytosine (GC or GG rather than CC), the V617F mutation is far more likely to arise (around 3.7 times more frequently than if the predisposing haplotype was not present). Why this happens is not known. MPN arising in non-46/1 haplotypes is not phenotypically different to that arising in 46/1 haplotypes.

A similar situation can be seen with Facioscapulohumeral dystrophy (FSHD), except that here the effect of the predisposing haplotype is even more dramatic. FSHD is caused by the accumulation of a toxic protein in muscle cells called DUX4. The DUX4 gene is present next to a microsatellite region called D4Z4 on chromosome 4q35 and is ordinarily not transcribed. Most subjects have 11-100 D4Z4 repeats of CpG and GpC nucleotide base sequences. Subjects with FSHD have only 1-10 such repeats in the D4Z4 region ("contraction" of D4Z4 region). The D4Z4 microsatellite region can be identified by digestion of DNA with a restriction endonuclease called EcoR1.

However D4Z4 is not exclusive to chromosome 4. This microsatellite sequence is also located on chromosome 10. However, here the contraction of the D4Z4 region does not lead to FSHD.

Here's the important bit. Simply having a contracted D4Z4 region on 4q35 will not lead to FSHD. For that to happen, you need a permissive haplotype located just next to the D4Z4 region called 4qA 161 (or rarely, some other 4qA haplotypes). If the person involved has a haplotype containing 4qB rather than 4qA or a non-permissive 4qA haplotype, FSHD will not develop.

Why does this happen? 4qA 161 is responsible for generating the polyadenylate (polyA) tail at the 3' end of the DUX4 mRNA that stabilises it and leads to its translation. Without the polyA tail, the mRNA would be unstable and would be destroyed.

Interestingly in procaryotes such as bacteria, the polyA tail serves the exact opposite function. Polyadenylated mRNA are tagged for destruction.

So why does contraction of the microsatellite D4Z4 region lead to de-repression of the toxic DUX4 mRNA? It is thought that the full length D4Z4 region keeps the DUX4 gene in a "compressed" state. In FSHD, the briefer D4Z4 sequence allows uncoiling of the DUX4 gene and its subsequent transcription, providing of course the polyA tail from the permissive 4qA 161 haplotype was also available.

Men Should Receive Lifelong Anticoagulation Following Unprovoked DVT or PE

The current standard of care is to treat subjects who have a provoked venous thromboembolism (VTE-either DVT or PE) with anticoagulation for 3 months. In those who have an unprovoked VTE (no history of leg fracture, leg in cast, immobility for > 3 days, major surgery within 3 months or diagnosed cancer) for 6 months. However, many subjects in this latter group have "catch-up" thromboembolism once anticoagulation is stopped.

Two observations should prompt a change in current practice.

Firstly, several studies, particularly two papers published in 2008 and 2016 from Canada, have shown that men run a far higher risk of recurrent DVT/PE over a follow up period of around 5 years after stopping anticoagulation following an index event. (7.6% annually in men v 2.8% in women). The average risk of repeat VTE in the first year is around 10% when both genders are combined. In the second year, this falls to 5%. Subsequently, the risk remains constant at around 3% per year. Over 8 years, the cumulative risk of recurrent VTE across both genders is ~30%. For men, this risk is higher at around 40%.

Women are not completely safe, however. Among women, using a risk stratifier called HERDOO2 (explained soon), women with 0 or 1 risk factors had a very low risk of recurrent VTE after stopping anticogulation, while women with 2 or more risk factors, had a risk of recurrent VTE only slightly lower than men (approximately 1% annually in low risk women and 6% in high risk women).

HERDOO2 includes HER-Hyperpigmentation, pretibial Edema, and Redness, all indicators of post thrombotic syndrome measured at ~6 months after the index DVT or PE in either leg. D is serum D-Dimer of >250 ug/ml, measured while on anticoagulation, the first O is Obesity (BMI>30) and the 2nd O is for Old age (>65 years).

HERDOO2 should only be used to risk stratify women. All men are at a higher risk of recurrent VTE.

Across all risk groups, continuing anticoagulation reduces the risk of a repeat VTE episode by around 80%.

What about mortality benefit? In low risk women, the risk of dying from major haemorrhage while on anticoagulation is around the same as the risk of dying from recurrent VTE if anticoagulation is stopped after 6 months. However, in men and high risk women, continuing anticoagulation reduces the risk of death from repeat VTE from 1.4% over 8 years to less than 0.3%. The risk of dying from a major bleed while on anticoagulation over the same period is 1.1%.

The second observation comes from two recent papers that show that in subjects receiving newer oral anticoagulants (NOACs), maintenance treatment with low dose NOAC (10 mg with rivaroxaban or 2.5 mg BD with apixaban daily) has the same benefit in terms of VTE prevention as maintenance with full dose NOAC (20 mg of rivaroxaban or 5 mg BD of apixaban daily) with similar or lower risk of bleeding as placebo (in the first study) or aspirin (in the second study), although the risk of bleeding in general was low across all treatment groups. All subjects received full dose NOAC for the first 6-12 months after the index VTE.

There is thus a strong case for maintaining men and high risk women with unprovoked VTE on lifelong low dose apixaban or rivaroxaban after an initial 6-month period of full dose anticoagulation. Current practice needs to change.

References.
1. Rodger MA, Scarvelis D, Kahn SR, et al. Long-term risk of venous thrombosis after stopping anticoagulants for a first unprovoked event: a multi-national cohort. Thromb Res 2016;143:152-158
2. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708
3. Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. DOI: 10.1056/NEJMoa1700518

Non-Intuitive Medicine: Using Anti-D to Treat ITP

Most people are aware of the consequences of Rhesus incompatibility. It's usually the 2nd pregnancy. The mother is Rhesus negative. The father is Rhesus positive and has the D antigen. The foetus inherits the D antigen from the father. The mother's immune system mounts an attack on the D iso-antigens in the child's blood, resulting in haemolysis, sometimes ending fatally in erythroblastosis foetalis.

Now countenance this. Would you consider infusing a patient known to be Rhesus positive with pre-formed antibodies to the Rhesus(D) antigen, deliberately risking haemolysis?

No, I thought not.

Yet, that is exactly what happens in in subjects with severe Idiopathic Thrombocytopenic Purpura (ITP) who have life threatening haemorrhage. If the patient is D+, he/she is infused with anti-D containing immunoglobulin. IgG antibodies to the D antigen agglutinate the subjects' RBCs. Macrophages, mainly in the spleen, recognise the Fc portion of the anti-D immunoglobulins to bind to the D antigen on RBC and take them up actively. In so doing, the reticulo-endothelial system becomes saturated with millions of antibody-agglutinated RBC and is no longer free to bind to and destroy the platelets.

Medicine in reverse.

Of course, a better known agent for treating ITP is intravenous immunoglobulin (IVIG). It was from observing the small incidence of haemolysis in subjects receiving IVIG that the idea of using anti-D arose. Anti-D has a number of advantages over IVIG. These include a substantially shorter infusion time, markedly smaller infusion volume, longer duration of response demonstrated in HIV-infected patients with ITP, lower cost, and exposure to 1/100th as many donors per dose. Increased platelet count is seen in 70-80% of patients receiving anti-D. The dose is 50-75 ug/kg. It is licensed for this purpose in the USA but not in Europe, where plasmapheresis and romiplostim (thrombopoetin agonist) are used in addition to IVIG for treating major bleeding (intracranial or gastrointestinal) in severe ITP.

Anti-D is not without its dangers with such usage. Approximately 1 in 1000 patients develop severe transfusion reactions, with extravascular haemolysis, and increased risk of DIC and acute renal failure. This has resulted in a Black Box warning being issued by the FDA for such usage. However, in most patients, the degree of haemolysis is mild, with Hb dropping by 0.5-2g within a week, and recovering by 3 weeks.

Understandably, anti-D should not be used in those with pre-existing haemolysis, in those with a positive Coomb's test or those with renal impairment. It is ineffective in those who have had a splenectomy. Some haematologists never use anti-D despite its advantages, and prefer IVIG instead.

IgG anti-D does not bind complement. There is therefore no intravascular haemolysis. Haptoglobin and haemopexin do not fall.

References:

1. Despotovic JM, Lambert MP, Herman JH et al. RhIG for the treatment of immune thrombocytopenia: consensus and controversy. Transfusion 2012;52:1125-6.

Testosterone Replacement Therapy & Risk of Prostate Cancer

Hormone sensitive metastatic prostate cancer is treated with androgen deprivation therapy, typically with gonadotropin releasing hormone analogues, which essentially turn off the pituitary release of luteinizing hormone through sustained stimulation (as opposed to pulsatile release, which is physiological). This results in chemical castration.

The issue assumes relevance when you consider the practice of testosterone replacement therapy (TRT). In recent years, TRT has become popular among primary care physicians, as a sort of panacea for fatigue, lassitude and muscle wasting, particularly in elderly subjects. The FDA recently mandated that preparations for TRT explicitly carry a warning against a higher risk of myocardial infarction and stroke in users. Nevertheless, a subset of subjects with low serum testosterone genuinely benefit from TRT, particularly when associated with diminished libido, or loss of morning or nocturnal erection despite being otherwise healthy, a condition known as adult onset hypogonadism. Such subjects have low total and free serum testosterone and normal LH levels.

When such subjects are elderly, as they often are, it is logical to ask whether such TRT increases the risk of causing hormone sensitive cancers in the future. In fact, TRT can increase the likelihood of developing breast cancer in those who have another risk factor such as BRCA1 or 2 or Cowden's syndrome. However, such cancers are very uncommon. A much more relevant concern is whether TRT stores up a future risk of prostate cancer.

In a disease which, when metastasised, is treated with surgical, or more commonly, chemical castration, it therefore came as a surprise to learn from RCTs that firstly, low testosterone levels were associated with a higher risk of prostate cancer. Secondly, subjects with adult onset hypogonadism had more advanced prostate cancer at diagnosis by stage, grade and volume. Thirdly, TRT was not associated with a higher risk of prostate cancer in any RCT.

Reference

Mayo Clinic Proceedings, Vol. 91, Issue 7, p908–926

Right Colectomy in Mucocoele of the Appendix to Prevent Pseudomyxoma Peritonei

Appendiceal mucocoele is most often caused by benign mucinous cystadenoma, and less commonly by mucinous adenocarcinoma. The commonest malignant tumour of the appendix used to be carcinoid. This is now changing, as mucinous adenocarcinoma becomes more common.

When mucocoele of the appendix is diagnosed, usually incidentally during cross sectional imaging, it mandates appendicectomy. Untreated, appendiceal mucocoeles can rupture, leading to pseudomyxoma peritonei (PMP), an incurable condition.

PMP caused by rupture of mucocoele is also called Disseminated Peritoneal Adenomucinosis or DPAM. Most authorities only use the term PMP when the underlying aetiology is DPAM. However, others use the term PMP to desribe the dissemination of mucin producing cells from carcinomas of the appendix or colon. The distinction is important, because the latter has a materially worse prognosis.

PMP has a striking appearance on imaging. On CT, mucin has the same appearance as water, but in addition, there is widespread calcification, scalloping of the liver and spleen, with a predominantly peripheral distribution of lesions.

PMP is difficult to treat. Repeated cytoreductive surgery (CRT) is required. An approach that is gaining in popularity among surgeons is cytoreductive surgery followed by Heated Intraperitoneal Chemotherapy or HIPEC. The latter involves intraoperative infusion of dialysis fluid containing mitomycin C, heated to 41 degree Celsius to increase penetration of tumour deposits. However, even with heating, the chemotherapeutic agent is unable to penetrate beyond a couple of millimeters.

Pioneering work in this area has been done by Sugarbaker & colleagues. They found that pre-operatively, the prognosis was worse when there was segmental obstruction of the jejunum or proximal ileum or if the peritoneal deposits exceeded 5 mm in size.

When CRT with HIPEC is used, it is standard to follow through with postoperative intra-peritoneal fluorouracil.

Untreated. PMP is fatal as intraperitoneal mucin accumulates inexorably and causes intestinal obstruction. The most well known victim was Audrey Hepburn, who succumbed to this condition.

PMP is more common in women. In the article in JAMA Surgery referenced below, the tumour (mucinous cystadenoma) involved the base of the appendix. To avoid spilling mucin intra-operatively and thus cause PMP, resection margins must be clear. Thus, right colectomy was opted for rather than a simple appendicectomy.

This is an example of a benign tumour behaving like a malignant one.

(Free access is available to most articles in all JAMA group journals through a single registration giving access to the JAMA Network Reader. Thank you, the American Medical Association).

References.

1. http://learningradiology.com/notes/gunotes/pseudomyxomacorrect.htm
2. http://jamanetwork.com/journals/jamasurgery/article-abstract/2601315
3. UpToDate