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We demonstrate quantum logic enhanced sensitivity for a macroscopic ensemble of solid-state, hybrid two-qubit sensors. We achieve over a factor of 30 improvement in the single-shot signal-to-noise ratio, translating to an ac magnetic field sensitivity enhancement exceeding an order of magnitude for time-averaged measurements. Using the electronic spins of nitrogen vacancy (NV) centers in diamond as sensors, we leverage the on-site nitrogen nuclear spins of the NV centers as memory qubits, in combination with homogeneous and stable bias and control fields, ensuring that all of the ∼10^{9} two-qubit sensors are sufficiently identical to permit global control of the NV ensemble spin states. We find quantum logic sensitivity enhancement for multiple measurement protocols with varying optimal sensing intervals, including XY8 and DROID-60 dynamical decoupling, as well as correlation spectroscopy, using an applied ac magnetic field signal. The results are independent of the nature of the target signal and broadly applicable to measurements using NV centers and other solid-state spin ensembles. This work provides a benchmark for macroscopic ensembles of quantum sensors that employ quantum logic or quantum error correction algorithms for enhanced sensitivity.

Background: Genealogy and molecular genetic studies of a Swedish river valley population resulted in a large pedigree, showing that the hereditary hemochromatosis (HH) HFE/p. C282Y mutation is inherited with other recessive disorders such as Wilson´s disease (WND), a rare recessive disorder of copper overload. The population also contain individuals with the Swedish long QT syndrome (LQTS1) founder mutation ( KCNQ1 /p.Y111C) which in homozygotes causes the Jervell & Lange Nielsen syndrome (JLNS) and hearing loss (HL).Aims of the study were to test whether the Swedish long QT founder mutation originated in an ancestral HFE family and if carriers had an increased risk for hemochromatosis (HH), a treatable disorder. We also aimed to identify the pathogenic mutation causing the hearing loss disorder segregating in the pedigree., Methods: LQTS patients were asked about their ancestry and possible origin in a HH family. They were also offered a predictive testing for the HFE genotype. Church books were screened for families with hearing loss. One HH family had two members with hearing loss, who underwent molecular genetic analysis of the LQTS founder mutation, connexin 26 and thereafter exome sequencing. Another family with hearing loss in repeat generations was also analyzed for connexin 26 and underwent exome sequencing., Results: Of nine LQTS patients studied, four carried a HFE mutation (two p.C282Y, two p.H63D), none was homozygous. Three LQTS patients confirmed origin in a female founder ( b 1694, identical to AJ b 1694, a HFE pedigree member from the Fax river. Her descent of 44 HH families, included also 29 families with hearing loss (HL) suggesting JLNS. Eleven LQTS probands confirmed origin in a second founder couple (b 1614/1605) in which the woman b 1605 was identical to a HFE pedigree member from the Fjällsjö river. In her descent there were not only 64 HH, six WND families, one JLNS, but also 48 hearing loss families. Most hearing loss was non syndromic and caused by founder effects of the late 16 th century. One was of Swedish origin carrying the WHRN, c.1977delC, (p.S660Afs*30) mutation, the other was a TMC1 (NM_138691),c.1814T>C,(p.L605P) mutation, possibly of Finnish origin., Conclusions: Deep human HFE genealogies show HFE to be associated with other genetic disorders like Wilson´s disease, LQTS, JLNS, and autosomal recessive hearing loss. Two new homozygous HL mutations in WHRN /p.S660Afs*30 and TMC1/ p.L605P were identified,none of them previously reported from Scandinavia. The rarity of JLNS was possibly caused by miscarriage or intrauterine death. Most hearing loss (81.7%) was seen after 1844 when first cousin marriages were permitted. However, only 10 (10.3%) came from 1 st cousin unions and only 2 (2.0 %) was born out of wedlock., Competing Interests: The study was approved by the Regional Ethical Review Board at the University of Göteborg, (Dnr 834/14) ,T 214/16 and T1076-16). Consent for publication of hearing loss and LQTS was obtained.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The coupling and possible nonequilibrium between magnons and other energy carriers have been used to explain several recently discovered thermally driven spin transport and energy conversion phenomena. Here, we report experiments in which local nonequilibrium between magnons and phonons in a single crystalline bulk magnetic insulator, Y_{3}Fe_{5}O_{12}, has been created optically within a focused laser spot and probed directly via micro-Brillouin light scattering. Through analyzing the deviation in the magnon number density from the local equilibrium value, we obtain the diffusion length of thermal magnons. By explicitly establishing and observing local nonequilibrium between magnons and phonons, our studies represent an important step toward a quantitative understanding of various spin-heat coupling phenomena.

Unlabelled: Wilson's disease (WND) and hereditary hemochromatosis (HH) are two metal loading diseases of copper and iron, respectively, and are both recessively inherited. In central Sweden, where HH is common, 9 Wilson kindred (14 members) were identified. Aims of the study were to test whether nine WND families shared a common origin, a common mutation and if carrying HFE mutations affected their phenotype., Results: The nine families were traced through 13 generations to a common founder origin in the mid-seventeenth century. Despite identity of descent, four different ATP7B mutations appeared with homozygosity in four, with two different mutations, W779X and T977M. There were three compound heterozygotes, W779X/T977M, R1319X/H1069Q and one T977M combined with a new, previously not described mutation, probably of Finnish origin. The founder family also included 26 descendant kindred (55 members) with HH as shown by HFE mutations. This admixture coincided with a migration out of the original parish into hemochromatosis-rich localities. One WND patient had iron overload (serum ferritin 672 µg/l and raised liver enzymes), but lacked HFE mutations. In another family with serious hemochromatosis (two sons dying from bronze diabetes), the coinheritance of congenital spherocytosis was probably the cause rather than an additional effect of WND., Conclusions: WND though a rare disease may become aggregated like HH in certain areas due to local founder effects. Despite extensive pedigree studies leading back to the local founder family, the authors were unable to find a single defining mutation of the ATP7B gene.

Unlabelled: The HLA-related hemochromatosis mutation C282Y is thought to have originated in Ireland in a person with HLA-A3-B14 and was spread by Vikings. Irish people with two HLA-A3 alleles had a high risk of hemochromatosis. In this study, from west Sweden, we wanted to test these hypotheses., Methods: HFE mutations in controls, bone marrow donors with HLA-A3/A3 and patients with hemochromatosis. HLA haplotypes, extended haplotype analysis and pedigree studies., Results: The allelic C282Y frequency 0.04, (CI 0.01-0.07) was lower (P < 0.001) in Sweden than in Ireland 0.10 (CI 0.08-0.11), and Swedish bone marrow donors with HLA-A3/A3 (n = 77) had a low risk of hemochromatosis. HLA haplotypes available from 239/262 (91.5%) proband patients homozygous for C282Y showed a dominance of A3-B7 and A3-B14 both in linkage disequilibrium with controls (P < 0.001). Pedigree studies extended into the 17th century supported a local founder effect of A3-B14 in the county of Bohuslän. The A3-B14 haplotype may well be the original and A3-B7 the result of centromeric recombinations. The haplotype diversity and recombination events were not different from a Celtic series. These findings do not support the hypothesis of the C282Y mutation being of an Irish Celtic origin., Conclusions: The C282Y frequency shows a west to east decline from Ireland through the north of Europe. Vikings may have been involved in the spread of C282Y, but the mutation is probably older and may have been spread in Europe by earlier seafarers., (© 2010 John Wiley & Sons A/S.)

Background: The haemochromatosis mutation C282Y occurred once in a person who lived in Ireland or Scandinavia and carried either human leucocyte antigen (HLA)-A3-B7 or A3-B14. With time, recombinations are believed to have taken place introducing new HLA haplotypes. This evolution is mainly unknown. In this study, we tried to find a founder, possible recombination events and effect on the phenotype in descendants., Setting: A Swedish mountain population close to Norway, n = 3529, population density <1/km(2)., Methods: Retrospective genealogy study of HLA haplotypes followed by extended haplotype studies., Results: There were 34 probands (22 men, 12 women) where 31 (91%) shared a common founder origin 12 generations ago. The A3-B14 haplotype was the most common, 39%, in strong linkage disequilibrium (P < 0.0005) with controls, followed by A3-B7, 20% (P < 0.005), probably resulting from a centromeric recombination replacing the B14 allele with the common B7. Possible telomeric recombinations took place close to HLA-A and introduced the haplotypes AW19-B7 (n = 4), AW19-B27 (2), A1-B17 (5) and A2-B12 (4) supported by pedigree studies. Male homozygotes with two copies of HLA-A3 had significantly (P 0.001) higher mean serum ferritin values than those with one, and liver damage (fibrosis and cirrhosis) was also more common (P < 0.001) than in a population with a recombinant (A1-B8) haplotype., Conclusions: A3-B14 may well be the ancestral haplotype with A3B7, the result of centromeric recombinations introducing the common B7 allele. Telomeric recombinations were more common than expected. The ancestral HLA-A3 haplotype may be associated with a more severe phenotypic expression.

Background: The hemochromatosis mutation, C282Y of the HFE gene, seems to have originated from a single event which once occurred in a person living in the north west of Europe carrying human leukocyte antigen (HLA)-A3-B7. In descendants of this ancestor also other haplotypes appear probably caused by local recombinations and founder effects. The background of these associations is unknown. Isolated river valley populations may be fruitful for the mapping of genetic disorders such as hemochromatosis. In this study, we try to test this hypothesis in a study from central Sweden where the haplotyope A1-B8 was common., Methods: HLA haplotypes and HFE mutations were studied in hemochromatosis patients with present or past parental origin in a sparsely populated (1/km(2)) rural district (n = 8366 in the year of 2005), in central Sweden. Pedigrees were constructed from the Swedish church book registry. Extended haplotypes were studied to evaluate origin of recombinations., Results: There were 87 original probands, 36 females and 51 males identified during 30 yr, of whom 86% carried C282Y/C282Y and 14% C282Y/H63D. Of 32 different HLA haplotypes A1-B8 was the most common (34%), followed by A3-B7 (16%), both in strong linkage disequilibrium with controls, (P < 0.001). Twenty-nine different families with A1-B8 had a common founder origin 15 generations ago in small bottleneck populations of the late 16th century. A second A1-B8 founder born 1655 was of Norwegian origin. Most of the A3 carriers (n = 26) had a common founder origin 16 generations ago in an even smaller nearby river valley. A fourth founder family carrying HLA-A2 seems to have originated from a recombination along the descendant lines from the A3 ancestor supported by extended haplotype studies. A1-haplotypes with alleles at the B locus different from B8 had a similar recombination origin as HLA-A2 alleles and a common founder origin 11 generations ago. The intergenerational time interval averaged 35.5 +/- 7.9 yr in men and 31.9 +/- 5.9 in females., Conclusions: River valley populations may contain HLA haplotypes reflecting their demographic history. This study has demonstrated that the resistance against recombinations between HLA-A and HFE make HLA haplotypes excellent markers for population movements. Founder effects and genetic drift from bottleneck populations (surviving the plague?) may explain the commonness of the mutation in central Scandinavia. The intergenerational time difference >30 yr was greater than expected and means that the age of the original mutation may be underestimated.

Background: Hemochromatosis is a recessively inherited disorder caused by a point mutation, C282Y of the HFE gene on chromosome 6p21.3 near the human leukocyte antigen (HLA) locus. It is unknown why some homozygotes develop a severe iron loading, while others do not. A recent study suggested that the A1-B8 haplotype may be associated with higher iron storage., Methods: We studied HLA haplotypes of 85 probands, 31 females and 54 males, and their family members from a rural population where A1-B8 was common. We tested the hypothesis of a modifying effect of the A1-B8 haplotype., Results: Most homozygotes had a mild phenotypic expression, and were often detected accidentally because of a laboratory routine including transferrin saturation. A disease-related morbidity [serum alanine aminotransferase (S-ALT) > 43 U] was present in 40%. Three had porphyria cutanea tarda. Two brothers with A1-B8 died of bronze diabetes, probably caused by co-inheritance of congenital spherocytosis. In females there were no significant differences in phenotypic expression between groups with regard to the presence or absence of A1-B8. Two females, <50 yr of age, with this haplotype had iron deficiency. Males with two copies of A1-B8 had significantly lower serum ferritin (P = 0.02) values than those without. Those with one A1-B8 haplotype were not different from those without. In men without A1-B8, those carrying HLA-A3 were not phenotypically different from those without this ancestral haplotype., Conclusion: The A1-B8 haplotype hitchhiking with the C282Y mutation was not associated with a more efficient iron absorption. On the contrary, males with double copies of this haplotype expressed a milder phenotype, possibly an effect of local (environmental and/or genetic) factors.

Objectives: The present study was undertaken to confirm or reject recent findings indicating a high prevalence of iron deficiency in Swedish male adolescents; a second aim was to study the prevalence of genetic iron overload., Design: The diagnostic criteria were: anaemia: Hb < 130 g L-1 (a): iron deficiency: serum ferritin (SF) < 12 micrograms L-1 + transferrin saturation (TS) < 16% (b): iron deficiency anaemia a + b. Iron overload: SF (90th percentile) + TS (90th percentile) in repeat tests., Setting: Central Sweden., Subjects: A total 3975 men aged 18 years studied on enrollment into military service., Results: Serum ferritin averaged 36.8 micrograms L-1. Anaemia was present in 0.5%, iron deficiency anaemia in 0.17% and iron deficiency in 0.4%. If iron deficiency is defined as SF < 16 micrograms L-1, as was recently suggested, the prevalence would be 2.8%. Such a cut-off value would include 73% normal people (false positives). Iron overload had the same prevalence as iron deficiency, 0.4%., Conclusions: Iron stores, as measured by serum ferritin, are small in young men studied at the end of their growth spurt. However, iron deficiency is rare. Therefore, the present study has not been able to confirm the high prevalence of iron deficiency recently reported. A prevalence of genetic haemochromatosis of 0.4%, confirms earlier findings and would mean that 12.6% of the population are heterozygotic carriers of the iron-loading genes. These findings give no support for a proposed, more effective iron-enrichment of food. It is not needed and can be harmful.

The characteristics of iron stores built up by a new parenteral iron-poly (sorbitol-gluconic acid) complex, Ferastral, have been studied in iron depleted non-anemic blood donors. The results from studies on the first three subjects are presented. The availability of this storage iron for the chelator, desferrioxamine, was found to be in the same range as normal iron stores. The pattern of distribution in reticulo-endothelial cells of the bone marrow could not be differentiated from natural storage iron. No visible iron could be detected in liver parenchymal cells 40 days after iron administration. The results from these preliminary studies suggests normal bioavailability of this material for Hb-synthesis. The absence of iron in liver parenchymal cells might be explained by the short time interval between the iron administration and the fine needle aspiration biopsy.

Liver dysfunction as measured by S-ALAT activity was present in 72% of patients over 40 years of age with HLA-related iron overload, mainly detected by laboratory screening. Liver dysfunction was correlated to the amount of iron stored (r = 0.54, p less than 0.001). When iron was removed by phlebotomy, liver function returned to normal. S-ALAT activity was closely correlated to serum ferritin concentration (r = 0.73, p less than 0.001). Even a mild iron excess can affect hepatocytes and result in increased levels of ferritin and aminotransferases in serum. Patients with "transaminitis" should be investigated for iron overload.

The frequency of HLA-A3 and HLA-B14 antigens was found to be significantly (P = less than 0.0001) higher in a series of 50 unrelated and unselected Swedish patients with idiopathic hemochromatosis (IH) than in controls, being 66% and 32% for A3 and 22% and 2% for B14. The haplotype A3B14 was associated with the highest risk in this material (relative risk 23.4). One family with this haplotype was traced back to the end of the seventeenth century. The pattern of HLA antigens associated with IH in Sweden shows remarkable similarity to those reported from England and Brittany.

The gene coding for idiopathic hemochromatosis is prevalent in Sweden, the country with the highest iron fortification of food (42%) in the world. We wanted to study if this highly iron-fortified diet had negative effects on the iron situation in carriers of the iron-loading genes. Iron stores averaged 6.7 grams in male homozygotes who were mainly identified through laboratory screening. It was 3.4 grams in female homozygotes. By HLA typing of family members of these homozygous probands, 39 additional homozygotes and 172 heterozygotes were detected. Serum ferritin averaged 620 micrograms/l in 20 male and 168 micrograms/l in 19 female homozygotes in the family screening. Storage iron as measured by serum ferritin concentration was slightly but significantly higher in male heterozygotes than controls (117 micrograms/l versus 87 micrograms/l, p less than 0.02). There was no further increase in serum ferritin concentration with age after 40 years. Heterozygotes showed no clinical signs of iron damage. These findings do not indicate that carriers of the iron-loading genes in Sweden have been adversely affected by the highly iron-fortified diet of the country.

Three hundred forty-seven (96.4%) of all persons aged 30 to 39 years were screened with serum iron and iron binding capacity measurements to determine the incidence of hemochromatosis in a population. No women had signs of iron overload; however, nine men (5%) had persistenly elevated serum iron levels. In four men (2%), increased iron stores was found with a distribution like that in the early stages of hemochromatosis. In combination with recent findings of clinical hemochromatosis at our hospital, this study suggests that this condition is not as rare as has been reported earlier.

An increase in the iron content of food may be harmful to people with genetic hemochromatosis. We studied the prevalence of this disorder in Sweden, which is the country with the world's highest iron fortification of food. Serum ferritin and transferrin (TIBC) saturation levels were used as initial screening methods. Three (0.5%) of 623 males aged 30-39 years were found to have genetic hemochromatosis. Family studies revealed 10 additional homozygotic family members. A prevalence of 0.5% of homozygotes (q2) implies a gene frequency (q) of 6.9% or a heterozygote frequency (2 x Q) of 13.8%. The high gene frequency may be explained by a possible genetic advantage of heterozygotes in the past. We conclude that idiopathic hemochromatosis is not as rare as previously thought. Affected persons should be detected and treated before irreversible organ damage occurs. This study demonstrates that serum ferritin levels together with TIBC saturation levels are adequate methods for screening populations.

People with parenchymal iron overload exhibit an elevated serum iron concentration and a raised transferrin (TIBC) saturation early in the course of the disease. They can therefore be detected by simple laboratory tests before organ damage has occurred. In this study running for 2 months, 10512 samples from approximately 8750 patients and blood donors were examined in a county hospital in Central Sweden. Abnormal TIBC saturation (greater than 70%) was found in 1.7% of the samples. This abnormality was caused by physiological fluctuations in serum iron in 44%, liver disease in 22%, blood disorder in 10%, iron therapy in 10.5% and parenchymal iron overload in 11.5%. The diagnosis of iron overload was confirmed by measuring the serum ferritin concentration and by performing the desferrioxamine test, liver biopsy, quantitative phlebotomy and family studies including HLA typing. We found a prevalence of iron overload of 0.24%. This figure is almost certainly too low because some affected patients were probably lost because of TIBC desaturation induced by inflammatory conditions.